re: docket no. fda-2012-n- o public of website location of
TRANSCRIPT
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December 13, 2019
Dockets Management Staff (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852
Re: Docket No. FDA-2012-N-1021 for “Notice to Public of Website Location of
CDRH Fiscal Year 2020 Proposed Guidance Development.”
Dear Sir or Madam:
Medtronic appreciates the opportunity to submit comments on the Center for Devices and
Radiological Health’s (“CDRH’s”) Fiscal Year 2020 (“FY 2020”) Proposed Guidance
Development. On October 15, 2019, FDA established a docket where “interested persons may
comment on the priority of topics for guidance, provide comments and/or propose draft language
for those topics, suggest topics for new or different guidance documents, comment on the
applicability of guidance documents that have issued previously, and provide any other
comments that could benefit the CDRH guidance program and its engagement with
stakeholders.”1 Contemporaneously, FDA announced a website location where FDA posted two
lists of guidance documents that CDRH intends to publish in FY 2020.2 One of the Final
Guidance topics designated on that list as an “A-List” prioritized guidance document that CDRH
intends to publish in FY 2020 is “Labeling Recommendations for Surgical Staplers.”3
On May 30, 2019, FDA held an advisory committee meeting to discuss and make
recommendations regarding the reclassification of surgical stapler devices for internal use from
Class I (general controls) to Class II (special controls). Medtronic participated in and presented at
the advisory committee meeting, during which both testing and labeling special controls for
internal surgical staplers were discussed. After the meeting, Medtronic submitted comments to
the docket addressing FDA’s draft guidance on “Surgical Staplers and Staples for Internal Use—
Labeling Recommendations” (“Labeling Draft Guidance Docket”) and FDA’s proposed order on
“General and Plastic Surgery Devices; Reclassification of Certain Surgical Staplers.” As it is
relevant to the instant docket, a copy of that comment is attached as Appendix A.
Medtronic also understands that FDA currently is finalizing a rule to reclassify internal
surgical staplers from Class I to Class II, and will define a set of testing special controls for these
devices. Medtronic would like to take this opportunity to provide additional comments on that
1 See https://www.federalregister.gov/documents/2019/10/15/2019-22370/notice-to-public-of-
website-location-of-center-for-devices-and-radiological-health-fiscal-year-2020. 2 See id. 3 See https://www.fda.gov/medical-devices/guidance-documents-medical-devices-and-
radiation-emitting-products/cdrh-proposed-guidances-fiscal-year-2020-fy-2020#b.
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topic and on any draft guidance that may be provided addressing the special testing controls for
surgical staplers.
Medtronic supports reclassification of internal surgical staplers as Class II devices.
However, Medtronic is concerned that some of FDA’s proposals—most notably the potential
application of new testing controls to established products and certain clinical recommendations
included in the proposed labeling updates—will not enhance the safe use of surgical staplers and
may negatively-effect patient access and interfere with clinical decision making.
As further detailed in Medtronic’s comments to the Labeling Draft Guidance Docket,
product labeling is a critical component of Medtronic’s risk mitigation strategy for its internal
surgical stapling products. Medtronic believes that its current product labeling contains
appropriate warnings and instructions for use. While Medtronic supports FDA’s efforts to update
and standardize labeling for internal stapling devices across the industry, we believe that some of
FDA’s proposed labeling updates cross into the realm of surgical practice and potentially may
interfere with a surgeon’s decisions in the operating room (see pages 8-12 of our comments to the
Labeling Draft Guidance Docket for more discussion). These concerns were echoed by the Panel,
which recommended that the Agency work with medical societies, industry, and other stakeholders
to develop “special controls” that are clinically meaningful and do not interfere with medical
decision making.
Medtronic also is concerned about retroactively applying new testing controls to currently-
marketed stapling systems. Specifically, we submit that limited clinical value will be gained by
bench testing devices that have been in clinical use for many years and further, are concerned about
the potential adverse impact on device availability while testing and regulatory review takes place.
To address these concerns, Medtronic respectfully suggests that FDA limit the scope of its final
rule to new or modified devices, consistent with the Agency’s “Least Burdensome” guidance4 and
with its April 1, 2019 rule classifying in vitro diagnostic devices for Bacillus spp. detection.5
Medtronic currently has 23 internal stapling systems on the market in the U.S. Each of
these systems—including both the stapler and the staples—was developed, tested, manufactured,
submitted for clearance, and labeled consistent with FDA’s regulations and requirements for Class
II devices. In particular, each stapling system went through a comprehensive battery of pre-
clearance testing to predict its performance under expected clinical conditions and for the intended
indications, including testing for stability, sterility, biocompatibility, safety, and performance.
Most of these stapling systems have been in use for many years, during which time a large
body of clinical evidence has been developed regarding their real-world safety and effectiveness.
This evidence comes from a variety of sources, including clinical experience, complaint reports,
4 FDA, The Least Burdensome Provisions: Concept and Principles, Guidance for Industry and
Food and Drug Administration Staff, 4 (Feb. 5, 2019),
https://www.fda.gov/media/73188/download (hereinafter “FDA Least Burdensome
Guidance”). 5 See 84 F.R. 12083.
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case summaries, observational studies, and clinical trials. It is important to emphasize that this
evidence reflects actual clinical experience with our internal staplers, clinical data which
supersedes in quality and relevance any information that can be obtained from laboratory and
bench tests.
As Medtronic presented at the advisory committee meeting, the totality of this real-world
evidence confirms the consistent and favorable safety profile of Medtronic staplers. Death and
serious injuries associated with use of Medtronic staplers are rare (reported rates less than 0.0005%
and 0.017%, respectively), and, in most cases, are related to the inherent risks of the surgical
procedure, patient comorbidities, or the manner in which the device was used. Reported rates for
complaints related to Medtronic internal staplers have been stable over the last seven years without
any new safety signals, and, in fact, complaints involving serious injury have decreased by nearly
50%. Evidence from controlled studies and meta-analyses also consistently supports the favorable
safety profile of internal surgical staplers.
In this context, additional testing controls—such as further laboratory or animal studies—
are unlikely to provide any relevant, new information. At the same time, completing such testing
and evaluating its results will require a significant amount of time and resources, both on the part
of manufacturers and on the part of FDA. While that occurs, manufacturers may be forced to
temporarily (or even permanently) remove some surgical staplers from the market, resulting in
potential access issues for surgeons and health consequences for patients.
FDA has authority under Section 513(a)(1)(B) of the Federal Food, Drug, and Cosmetic
Act, to establish special controls for Class II devices to provide “reasonable assurance of the safety
and effectiveness.”6 However, as FDA has recognized, “Congress has directed [the Agency] to
take a least burdensome approach to medical device premarket evaluation in a manner that
eliminates unnecessary burdens that may delay the marketing of beneficial new products, while
maintaining the statutory requirements for clearance and approval.”7 In accordance with that
instruction, FDA has recommended leveraging existing data to provide “reasonable assurance of
safety and effectiveness” and has stated that “[a]lternative sources of clinical data should be
considered when appropriate, and, in many cases, may be the least burdensome means for
assessing device safety and effectiveness and for other regulatory decision-making.”8
Consistent with FDA’s Least Burdensome Guidance, Medtronic respectfully requests that
FDA exempt manufacturers of currently marketed internal staplers from submitting new 510(k)
submissions and from providing documentation of completion of the newly defined special testing
controls.9 FDA recently took this approach when classifying in vitro diagnostic devices
for Bacillus spp. as Class II, stating in its final rule that for “[d]evices that have been legally
marketed prior to the date of publication of this final rule, and devices for which 510(k) submission
6 Federal Food, Drug, and Cosmetic Act, § 513(a)(1)(B), 21 U.S.C. § 360c(a)(1)(B). 7 FDA Least Burdensome Guidance, 4. 8 Id. at 10. 9 This would not affect special labeling controls, which Medtronic believes should be applied
to both established and new devices in a consistent manner.
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have been submitted before the date of publication of this final rule … FDA does not expect
submission of documentation to FDA demonstrating compliance with the special controls set forth
in sections VI, VII, and IX of the special controls guideline.”10 A similar approach should be taken
here for manufacturers whose stapling systems have received clearance through the 510(k)
pathway, and have an established safety profile.
Medtronic is confident in the safety of our internal stapling systems, and we continue to
mitigate any potential risks associated with their use through product labeling, training, and device
innovation. We appreciate your consideration and look forward to working with FDA and other
stakeholders on this important issue.
10 See 84 F.R. 12083.
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APPENDIX A
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June 24, 2019
Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane, Rm. 1061 Rockville, MD 20852
Re: • Docket No. FDA-2019-D-1262, “Surgical Staplers and Staples for Internal
Use—Labeling Recommendations” • Docket No. FDA-2019-N-1250, “General and Plastic Surgery Devices;
Reclassification of Certain Surgical Staplers” Dear Sir or Madam: Medtronic appreciates this opportunity to submit comments to FDA’s draft guidance on “Surgical Staplers and Staples for Internal Use—Labeling Recommendations” and FDA’s proposed order on “General and Plastic Surgery Devices; Reclassification of Certain Surgical Staplers.” Medtronic supports FDA’s proposal to reclassify all internal surgical staplers as Class II devices, a regulatory determination that is consistent with Medtronic’s own practices. Medtronic also supports the Agency’s efforts to increase physician awareness and to enhance the safe use of internal staplers through implementation of uniform “special controls” across the industry. Medtronic took part in the May 30, 2019 meeting of the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee, during which the Panel considered a series of questions posed by FDA regarding reclassification of internal staplers and the Agency’s proposed labeling and testing “special controls.”1 Medtronic presented an analysis of the safety and performance data for its internal staplers, confirming both their favorable safety profile and the absence of any safety signals. Medtronic also discussed the programs that it has in place to mitigate risks associated with the use of surgical staplers, including product labeling, design innovation, and physician training. Finally, Medtronic provided an overview of its current pre-clearance testing program for internal staplers, which the Company believes meets or exceeds requirements outlined in FDA’s proposed reclassification order. Medtronic also raised concerns about some of FDA’s proposals. For example, Medtronic explained that conducting additional bench and animal testing on devices that have been in clinical use for many years and have an established safety profile is unlikely to provide clinically meaningful information and, in fact, may adversely affect patient access. Medtronic also noted that some of FDA’s proposed labeling updates cross into the realm of surgical practice and potentially may interfere with a surgeon’s decisions in the operating room. These concerns were echoed by the Panel, which recommended that the Agency work with medical societies, industry, and other stakeholders to develop “special controls” that are clinically meaningful and do not interfere with medical decision making. 1 Medtronic’s briefing book and its slide deck for the meeting are attached as Exhibits A and B to this document.
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Medtronic looks forward to partnering with FDA and other stakeholders to develop a reasonable and appropriate list of “special controls” for internal staplers and to address the Panel’s request for a uniform color coding system for all stapler reloads. A more detailed summary of Medtronic’s position and recommendations on this important issue is included below.
I. General Comments
Internal surgical staplers are revolutionary devices that have transformed the surgical experience for surgeons and patients and have become the standard of care for many surgical procedures. Surgical staplers decrease operative time, reduce the inherent variability of hand sutured constructs, and enable more complex surgical procedures. As FDA has observed, surgical staplers offer other important benefits, including “minimal tissue reaction, low risk of infection, [and] strong wound closure.”2 Each year, millions of Americans undergo surgical procedures to address a wide variety of medical problems, ranging from relatively minor health issues to life-threatening emergencies. In 2014, for example, there were more than 300,000 colorectal resections, 440,000 appendectomies, 950,000 cholecystectomies, 900,000 gastrointestinal surgeries, and more than 1 million cardiothoracic surgeries performed in the U.S.3 Surgeons rely on internal staplers each day to perform these and many other surgeries. It is estimated that internal staplers may be used in about six million surgical procedures each year. In the U.S., Medtronic’s internal staplers have been developed, tested, manufactured, submitted for clearance, and labeled consistent with FDA’s regulations and requirements for Class II devices. Prior to marketing, Medtronic conducts comprehensive testing on all of its internal stapling products. Consistent with FDA’s proposed guidance, Medtronic’s current pre-clearance program includes testing for: (1) stability; (2) sterilization/sterility assurance; (3) biocompatibility; (4) safety and performance in vivo, in vitro, and ex vivo; and (5) human factors/usability. For specific products, and as appropriate, Medtronic performs additional testing, including reprocessing validation, additional bench testing, software validation and verification, and electrical safety testing. After a stapler comes to market, Medtronic monitors its performance and safety through a robust quality system, which includes advanced design and manufacturing controls, and a comprehensive post-market vigilance program. As part of this process, Medtronic collects, evaluates, investigates, and reports customer complaints to FDA in accordance with the Agency’s regulations and guidelines. From 2001 to 2017, Medtronic took part in FDA’s alternative summary reporting (“ASR”) program for its internal surgical stapling products. During this time, on a quarterly basis, Medtronic submitted to FDA summary information on reportable malfunction complaints that did not involve an allegation of death or serious injury. In 2017, in conjunction 2 FDA, Surgical Staplers and Staples (Mar. 1, 2019), https://www.fda.gov/medical-devices/general-hospital-
devices-and-supplies/surgical-staplers-and-staples. 3 Steiner, C. et al., Surgeries in Hospital-Based Ambulatory Surgery and Hospital Inpatient Settings, 2014,
HCUP Statistical Brief #223, 10-11 (last updated February 2018), https://www.hcup-us.ahrq.gov/reports/statbriefs/sb223-Ambulatory-Inpatient-Surgeries-2014.pdf.
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with a transition from legacy Covidien to Medtronic complaint handling software, the Company stopped using ASRs for internal stapling products and resumed submitting individual medical device reports (“MDRs”) for all reportable malfunction complaints. Throughout this time, reportable complaints involving death and serious injury were submitted to FDA as individual MDRs, not through the ASR pathway.
The safety profile of Medtronic’s internal staplers has been established through decades of real-world use and study. Complications are infrequent and in most cases are related to inherent risks associated with the underlying surgical procedure, the patient’s comorbidities, and the manner in which the device is used. This is consistent with FDA’s observation that the most commonly reported causes of stapler complications are “the use of incorrectly sized staples, incorrect use of the device by the user and improper use of the device for the condition of the patient’s tissue,” rather than a defect in the device or its function.4 Numerous controlled studies support the favorable benefit-risk profile of internal surgical stapling devices.
In its proposed reclassification order, FDA reported that, during the period between January 1, 2011 and March 31, 2018, there were more than 41,000 complaints worldwide related to the use of internal staplers, including those manufactured by Medtronic.5 In order to put its own numbers into context, Medtronic analyzed its complaint database and calculated complaint reporting rates against total sales of its internal surgical stapling “firing” units. The results showed that complaint rates for Medtronic internal staplers have been, and continue to be, very low, averaging below 0.10%. Rates of reported customer complaints involving death and serious injury are lower—0.0005% and 0.0089%, respectively—consistent with expected complication rates associated with surgical procedures and general anesthesia. Over this period, the rates for reported complaints involving serious injury decreased by nearly 50%. It is important to emphasize that these rates are based on complaints received by Medtronic, not on confirmed events of device malfunction, patient injury, or death.
As part of the “Data Upon Which the Reclassification Is Based,” FDA also cited 33 articles published over the last 26 years containing information on safety outcomes with internal surgical staplers.6 Five of these were prospective studies, including more than 360 patients who underwent procedures during which Medtronic stapling devices were used. Among those patients, there were no deaths, fifteen reports of post-operative bleeding, one report of a post-operative anastomotic leak, and three reports of “misfires.”7 Of the 28 other articles that reported on surgical stapling procedures, sixteen (including 3,373 patients) reported on outcomes for procedures in which Medtronic stapling products were used. In those, there were no device-related deaths, six post- 4 FDA, Executive Summary, Reclassification of Surgical Staplers for Internal Use, 9 (prepared for the May 30,
2019 Meeting of the General and Plastic Surgery Devices Panel), https://www.fda.gov/media/126211/download (hereinafter “FDA Executive Summary”).
5 FDA, Proposed Order, General and Plastic Surgery Devices; Reclassification of Certain Surgical Staplers, 84 Fed. Reg. 17116, 1719 (Apr. 24, 2019) (hereinafter “FDA Proposed Reclassification Order”). At the Panel meeting, FDA updated these numbers to include both MDR and ASR reports between January 1, 2011 and December 31, 2018. The total number of complaints identified by FDA across the industry in this period was 109,997, including 412 complaints involving death, 11,181 involving serious injury, and 98,404 involving malfunction. See FDA Executive Summary at 13.
6 FDA Proposed Reclassification Order, 17122-23. 7 Summaries of the studies are included in Appendix 6 to Exhibit A .
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operative bleeds, thirteen post-operative anastomotic leaks, and 28 misfires or other device malfunctions.8 This body of evidence, spanning more than two decades, confirms the very low rates of complications and malfunctions associated with Medtronic’s internal stapling devices. The studies cited by FDA also suggest that complications are more common when surgeons are attempting new and/or more complex procedures, underscoring the importance of training at the residency, fellowship, and attending level. For example, Dresel et al. reported on outcomes of 100 patients who underwent Roux-en-Y gastric bypass procedures at a newly developed bariatric surgery program at a community hospital.9 The authors experienced numerous complications and three equipment malfunctions in the first 60 patients, but none in the last 40. They concluded that “Roux-en-Y gastric bypass is a technically challenging procedure that can be safely integrated into a bariatric treatment program with good results. Improved outcomes, shorter operative times, and fewer complications are associated with increased surgical experience.”10 Medtronic implements a variety of strategies to help increase physician awareness and to enhance the safe use of its internal staplers, including product labeling, design innovation, and training. Training is a point of particular emphasis. Medtronic offers a wide range of training opportunities for physicians at all levels of experience, including case observations, didactic lectures, and surgical simulations. Medtronic also supports training programs at the residency, fellowship, and medical society level and offers on- and off-site training to operating room staff. These strategies have been effective, and Medtronic supports FDA’s efforts to encourage similar practices across the industry. In particular, Medtronic supports FDA’s proposal to reclassify all internal surgical stapling products as Class II medical devices. Medtronic also welcomes the opportunity to work with FDA to develop consistent, clinically meaningful “special controls” for internal surgical stapling products and to address the Panel’s request for a uniform color coding system for all stapler reloads.
II. Specific Comments
While Medtronic supports FDA’s efforts to implement uniform “special controls,” Medtronic is concerned that some of FDA’s proposals—most notably the potential application of new testing controls to established products and certain clinical recommendations included in the proposed labeling updates—will not enhance the safe use of surgical staplers and may actually affect patient access and interfere with clinical decision making. As discussed in detail below, Medtronic respectfully requests that FDA amend its draft labeling guidance and proposed reclassification order to address both of these issues. Further, Medtronic asks that FDA work collaboratively with industry and professional societies to evaluate and address the Panel’s request for a uniform color coding system for all stapler reloads. 8 Summaries of the studies are included in Appendix 7 to Exhibit A . 9 Dresel, A. et al., Establishing a Laparoscopic Gastric Bypass Program, AM J SURG 2002;184(6):617-20. 10 Id. at 617.
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A. Special Controls Should Be Established in Accordance with FDA’s “Least Burdensome” Guidance
Pursuant to Section 513(a)(1)(B) of the Federal Food, Drug, and Cosmetic Act, FDA has authority to establish special controls for Class II devices to provide “reasonable assurance of the safety and effectiveness.”11 However, “Congress has directed FDA to take a least burdensome approach to medical device premarket evaluation in a manner that eliminates unnecessary burdens that may delay the marketing of beneficial new products, while maintaining the statutory requirements for clearance and approval.”12 With regard to “reasonable assurance of safety and effectiveness,” FDA has recommended leveraging existing data and has stated that “[a]lternative sources of clinical data should be considered when appropriate, and, in many cases, may be the least burdensome means for assessing device safety and effectiveness and for other regulatory decision-making.”13 These alternative sources include, for example, peer-reviewed literature, real-world evidence, well-documented case histories, and adverse event data.14 Medtronic believes that the “special controls” for internal staplers should be established in accordance with these principles and in a manner that is least likely to adversely affect patient access.
B. Medtronic’s Comments on Proposed Testing Controls
In its proposed reclassification order, FDA identified a series of proposed testing controls for internal surgical staplers. These fall into six general categories: (1) performance testing; (2) usability testing; (3) biocompatibility testing; (4) sterility testing; (5) validation of cleaning and sterilization for reusable devices; and (6) shelf-life testing. At the May 30, 2019 meeting, the Panel recommended excluding biocompatibility testing from this list and rewording the recommendations related to usability testing to avoid the implication that the manufacturer should be testing a surgeon’s ability to comprehend a product label. Medtronic proposed adding specific testing for powered devices, including electrical safety and software verification and validation.
As reflected in Exhibit C , FDA’s proposed testing controls appear to be consistent with Medtronic’s current testing program. Subject to the Panel’s recommendations and the additional comments included below, at a high level, the proposed testing controls appear to represent a reasonable approach for evaluating the safety and effectiveness of new internal stapling devices, i.e., those staplers that previously have not been cleared through the 510(k) process.
However, Medtronic believes these testing controls should not be applied retroactively to devices that already have been 510(k) cleared and have an established safety profile. Doing so will not provide clinically meaningful information, and may impact access to these devices. Medtronic believes that potential risks associated with the use of currently marketed internal staplers can be mitigated effectively through appropriate product labeling and training, consistent with Medtronic’s current practices. 11 Federal Food, Drug, and Cosmetic Act, § 513(a)(1)(B), 21 U.S.C. § 360c(a)(1)(B). 12 FDA, The Least Burdensome Provisions: Concept and Principles, Guidance for Industry and Food and Drug
Administration Staff, 4 (Feb. 5, 2019), https://www.fda.gov/media/73188/download (hereinafter “FDA Least Burdensome Provisions”).
13 Id. at 10. 14 Id.
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1. FDA’s Proposed Testing Controls Should Not Be Applied to Medtronic Devices Previously Cleared Through the 510(k) Process
Prior to being submitted for clearance, Medtronic’s internal staplers go through rigorous testing to evaluate their safety and performance. The testing primarily is conducted in the laboratory, in both animal and mechanical models, and is intended to “demonstrate that the stapler, when used with compatible staples, performs as intended under anticipated conditions of use.”15 In other words, the goal of the pre-clearance testing is to predict how the device will perform under real-world conditions, without the need for human test subjects. The results of the pre-clearance testing provide important information regarding clinical efficacy and safety. For example, testing of staple formation, staple line strength, and staple line integrity helps assess how effective the stapler is at transecting, resecting, and/or anastomosing tissue. Clinically, this translates into evaluating potential risks such as bleeding, anastomotic leaks, and fistula formation. Sterility testing is designed to ensure that the device does not contribute to infection risk, and usability testing is intended to assess how easy the device is to use. After Medtronic staplers have been in use for a number of years, real-world clinical evidence regarding their performance becomes available. This evidence comes from a variety of sources, including clinical experience, complaint reports, case summaries, observational studies, and clinical trials. Together, these data provide the most reliable evidence regarding a stapler’s safety and performance in humans, superseding pre-clearance laboratory and bench research. Medtronic currently has 23 internal stapling systems on the market, including laparoscopic and open, circular and linear, and mechanical and powered systems. All of these stapling systems were submitted for clearance through the 510(k) pathway, and their safety profile has been consistent and favorable over time. Death and serious injuries associated with use of Medtronic staplers are rare (reported rates less than 0.0005% and 0.017%, respectively), and, in most cases, are related to the inherent risks of the surgical procedure, patient comorbidities, or the manner in which the device was used. Reported rates for complaints related to Medtronic internal staplers have been stable over the last seven years, and, in fact, complaints involving serious injury have decreased by nearly 50%. Analysis of Medtronic’s complaint data did not identify any new safety signals across its stapler portfolio, including legacy and new devices as well as circular and internal staplers. Evidence from controlled studies and meta-analyses provides additional reassurance regarding the safety profile of these devices. The totality of available real-world data offers the most reliable evidence regarding the performance of Medtronic internal staplers and provides reasonable assurance of their safety and effectiveness. Additional laboratory testing and animal studies are unlikely to provide any new information to add to this body of evidence. The same is true for device registries, which were briefly mentioned during the Panel meeting. As Drs. William Meurer and Mike Miller explained, due to the wide range of stapling devices and potential clinical uses, the information generated from such registries would be difficult to interpret and is unlikely to enhance the safe use of these 15 FDA Executive Summary at 18.
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devices.16 Rather, potential risks associated with the use of Medtronic internal staplers can most effectively be mitigated through appropriate product labeling and training, consistent with Medtronic’s current practices. Finally, mandating new testing controls for Medtronic devices that previously have been cleared through the 510(k) process may impede patient access. As the Panel recognized, supply issues already exist for certain surgical stapling products.17 Imposing additional testing requirements—many of which are very time consuming and would have to be reviewed by FDA—may force Medtronic to temporarily (or even permanently) remove certain devices from the market. If that were to happen, surgeons would have fewer stapling options available for their patients. Such measures also would be contrary to Congress’ directive to “take a least burdensome approach to medical device premarket evaluation” and “eliminate[] unnecessary burdens that may delay the marketing of beneficial new products.”18
2. More Specifics Are Needed to Fully Evaluate FDA’s Proposed Testing Control
At a high level and subject to the Panel’s recommendations, the proposed testing controls appear to represent a reasonable approach for evaluating the safety and effectiveness of new internal stapling devices that have not been in clinical use. To ensure that the proposed testing is clinically meaningful and provides the “most efficient means of obtaining the evidence necessary to meet the regulatory need or standard”19 in accordance with FDA’s guidance, specifics regarding the standards, methods, and expected relevance of the proposed testing controls should be discussed and evaluated, with input from FDA, industry, and other stakeholders. For example, it is unclear what FDA intends to address through testing to measure “worst-case deployment pressures on stapler firing force.” Deployment pressure varies depending on tissue thickness and type and may be affected by a number of other factors. Medtronic is not aware of any standardized method of assessing or reporting this parameter. It also is unclear how this information would be used by physicians, or how the information would enhance the safe use of internal staplers. Medtronic hopes to meet with FDA and other stakeholders to discuss this and other details related to the proposed testing controls prior to a final reclassification order being issued. 16 A transcript of the Panel meeting was prepared by Medtronic and is attached as Exhibit D . See Exhibit D ,
69:3061-66 (“I would be I guess a little worried about how we would interpret the results of a registry and that if we have this registry, how would we -- how would we learn about the patient factors. These are very sick patients with very bad diseases, if you would have to try to do open sewing for anastomoses for example versus using a device. People die when they have open sewing procedures. Specific comparison group is a little challenging.”); 70:3118-22 (“I think if you try to create a registry and try to tease out where the surgeon role and the [role of the] device was, you try to find zero surgeon role because nobody report that if there was an outpatient, you know. So, I think the meaning on this data would be difficult to really understand.”)
17 See Exhibit D , 18:775-80. 18 FDA Least Burdensome Provisions at 4. 19 Id. at 14.
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C. Medtronic’s Comments on Proposed Labeling Updates
Product labeling is a critical component of Medtronic’s risk mitigation strategy for its internal surgical stapling products. While Medtronic believes that the current product labeling contains appropriate warnings and instructions for use, Medtronic welcomes the opportunity to work cooperatively with FDA and other stakeholders—including professional associations such as the Society of American Gastrointestinal and Endoscopic Surgeons (“SAGES”)—to develop a consistent framework for labeling across the class of internal stapling devices, with a focus on helping surgeons make appropriate choices for their patients. In doing so, it is important to make sure that product labeling and instructions for use do not interfere with clinical decision making and a physician’s ability to exercise his or her professional judgment. Medtronic also recognizes that FDA has warned about the risks associated with “overwarning,” explaining that “labeling that includes theoretical hazards not well-grounded in scientific evidence can cause meaningful risk information to lose its significance.”20 Further, as the Panel noted, including too much information in the product labeling (even if accurate) can make the labeling difficult to read and actually can reduce its value to physicians.21 Consistent with these principles and the Panel’s recommendations, Medtronic offers the following comments on FDA’s proposed labeling guidance. First, Medtronic believes that the information in Table 1 is not appropriate to include in labeling for internal staplers, as it extends into the realm of surgical practice and involves the application of medical judgement that appropriately is left to trained surgeons. Conditions and considerations vary from case to case and from patient to patient, and no single surgical approach is appropriate for all situations. Table 1: Information That Should Not Be Included in Stapler Labeling Contraindications • A statement noting that the device should not be used to
staple tissues that are necrotic, friable, or have altered integrity, e.g., ischemic or edematous tissues
Warnings • A statement to visually inspect for inclusion of unintended anatomic structures within the staple line
• A statement to avoid use of the stapler on large blood vessels, such as the aorta
• A statement to establish and maintain adequate proximal control of blood vessels prior to stapling
• A statement that clamping and unclamping of delicate structures such as venous structures and bile ducts may result in damage to tissue irrespective of stapler firing
• A statement that if a stapler malfunction occurs while applying staples across a blood vessel, then the user
20 FDA, Proposed Rule, Supplemental Applications Proposing Labeling Changes for Approved Drugs, Biologics, and Medical Devices, 73 Fed. Reg. 2848, 2851 (Jan. 16, 2008).
21 See Exhibit D , 28:1224-30, 30:1324-27.
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should clamp or ligate the vessel before releasing the stapler, while the stapler is still closed on the tissue
Directions for Use • The procedures for evaluating staple line formation and integrity
• The procedures for determining that a tissue is appropriate for stapling
Technical Characteristics and Performance Parameters
• Types of tissues on which the stapler and staples may be used
Second, as reflected in Table 2 below, a number of the proposed updates involve performance and technical parameters for which no standardized testing or reporting method exists. Absent a standardized approach across the industry, including such information is likely to be highly misleading. Further, for many of these, it is unclear how the information (if included in the labeling) would be used by physicians, or how it would enhance the safe use of internal staplers. Medtronic would like to discuss these recommendations with FDA and other stakeholders to determine whether a path forward exists, or whether to exclude them in the interest of making the labeling more focused on clinically relevant content for surgeons. Table 2: Technical Parameters That Are Not Standardized and Have Unclear Clinical Relevance Pre-firing compression time Burst strength Firing force
• These parameters all depend on tissue thickness and type and may be affected by a number of other factors.
• Medtronic is not aware of any standardized method for assessing or reporting these parameters.
Percentage of properly formed staples
• All Medtronic staplers are required to demonstrate 100% properly formed staples across the indicated range.
• Medtronic is not aware of any standardized method for assessing or reporting this parameter.
Angle(s) of articulation • The angle of articulation and the number of discreet adjustment points depend on the delivery handle used.
• Medtronic is not aware of any standardized format for measuring or reporting the angle of articulation for internal staplers.
Number of incremental firings required to complete a staple line
• The number of incremental firings required to complete a staple line depends on the clinical situation, the tissue being stapled, and the staple cartridge being used.
• The clinical relevance of this information is unclear.
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Shaft length • Effective shaft length depends on a number of factors, including the reload length and whether the shaft bends or not.
• Definition of shaft length can be subjective and lead to misleading labeling.
• Medtronic provides general information about the shaft, using the categories short, standard, and XL.
Third, due to space limitations, only a subset of the information in the product labeling can be included directly on the package. It is thus necessary to limit the information presented on the package to that which is both clinically relevant and capable of being summarized in a few words or images. With that in mind, Medtronic recommends not including information on staple pattern (limited clinical relevance) and safety mechanisms for tissue thickness (requires detailed instructions) on the packaging for internal staplers. To the extent applicable, that information is more appropriately included in the product labeling. Fourth, Medtronic does not believe that the direction to “ensure that the staples are compatible with the stapler” is appropriate for inclusion in the warnings section of the labeling. That information already is included in the compatibility section of the labeling, which lists the specific reloads that can be used with the stapler. Finally, Medtronic disagrees with inclusion of a statement to “ensure that no obstructions, such as clips, are incorporated into the instrument jaws when positioning the stapler on the application site” in the warning section of internal stapler labeling. Such a statement is likely to be confusing to physicians, as clinical circumstances exist in which it is necessary and appropriate to staple across an obstruction, e.g., a prior staple line.
D. Medtronic’s Comments on Color Coding of Stapler Reloads
At the May 30, 2019 meeting, the Panel asked FDA to evaluate whether it would be possible to standardize the color scheme used to identify different sizes of stapler reloads. While in principle Medtronic supports the proposal, more information is needed to assess the feasibility of developing a system that is both sufficiently simple to be useful to surgeons and sufficiently flexible to address the hundreds of different staple designs and sizes available across the industry. Prior to 1980, United States Surgical Company (a predecessor to Medtronic’s stapling business) introduced color coded reloads to help surgeons more easily identify the appropriately sized reload. In time, other manufacturers followed suit. While the colors evolved as new technology was introduced, over the past several decades, Medtronic has used the following colors for its standard staple reloads:
• Gray – vascular, extra thin (0.75 mm to 1.0 mm) • White – vascular, thin (1.0 mm to 1.5 mm) • Blue – medium thick (1.5 mm to 2.0 mm) • Green – thick (comfortably compressible to 2.0 mm)
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The colors are assigned based on staple performance across a range of tissues thicknesses, as assessed in bench and animal studies conducted prior to device clearance. Although similar color schemes are used by other manufacturers, it is unclear whether direct parallels in testing and indicated range can be made between Medtronic’s reloads and those of its competitors. Further complicating the issue, some reloads have unique sizes and designs that do not directly translate to other products sold by Medtronic or other manufacturers. For example, Medtronic’s Tri-Staple® technology reloads feature a stepped cartridge face with three rows of varied height staples and have a wider indicated tissue range than traditional reloads. Medtronic identifies these first-of-their-kind reloads with a unique color system, as described below:
• Gray – vascular, extra thin (0.75 mm to 1.0 mm) • Tan – vascular, medium (0.75 mm to 1.8 mm) • Purple – medium thick (1.5 mm to 2.25 mm) • Black – extra thick (2.25 mm to 3.0 mm)
The two color systems are summarized in Figure 1, below. Information on indicated tissue thickness and the related cartridge colors also is included in the product labeling for all Medtronic staple reloads. Figure 1: Color Schemes for Legacy Reloads and Reloads with Tri-Staple® Technology
For all these reasons, it is difficult to come up with a single color scheme that would be simple enough to be clinically useful and flexible enough to address all current and future staple sizes and designs. However, Medtronic is happy to take the lead on working with FDA, industry, and professional organizations to thoroughly assess the issue and evaluate potential options for addressing the Panel’s important request.
E. Other Comments on FDA’s Draft Labeling Guidance and Proposed Reclassification Order
In its proposed reclassification order, FDA identified four categories of “risks to health associated with the use of surgical staplers for internal use.” These include (1) complications associated with device failure/malfunction; (2) complications associated with use error/improper device selection and use; (3) adverse tissue reaction; and (4) infection. Consistent with the Panel’s recommendation, Medtronic believes that adverse tissue reaction should be eliminated from this
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list, as the stapler only has incidental contact with the patient. Further, Medtronic recommends that FDA include an additional category accounting for inherent risks related to the underlying procedure and patient comorbidities. A careful review of the evidence suggests that most complications reported with internal staplers are directly related to inherent risks of surgical procedures and patient comorbidities, rather than any defect in the device. Further, consistent with the Panel’s recommendation, Medtronic requests that any reference to an “increased risk of cancer recurrence” be removed from the draft guidance and proposed reclassification order. Cancer recurrence generally is a function of achieving clean margins at the time of surgery, and no reliable evidence exists suggesting that internal stapler use is associated with an increased risk of cancer recurrence.
III. Conclusion
Medtronic supports FDA’s proposal to reclassify all internal surgical staplers as Class II devices, a regulatory determination that is consistent with its own practices. Medtronic also supports the Agency’s efforts to increase physician awareness and to enhance the safe use of internal staplers through the implementation of uniform “special controls” across the industry. However, Medtronic respectfully requests that FDA reconsider several aspects of its proposal. First, Medtronic recommends that the proposed testing controls not be applied retroactively to Medtronic staplers that already have been cleared through the 510(k) process and have an established safety profile. Doing so will not provide clinically meaningful information, and may have a negative impact on patient access to these important devices. Second, as detailed above, Medtronic recommends that FDA revise its list of proposed labeling updates to remove information that is more appropriately left to the clinical judgment of trained surgeons. Third, questions remain as to the specifics of FDA’s proposed controls for internal staplers. Consistent with the Panel’s recommendation, Medtronic would welcome the opportunity to work cooperatively with FDA, medical societies, and other stakeholders to develop a final, clinically meaningful list of “special controls” for all internal staplers and to address the Panel’s request for a uniform color coding system for all stapler reloads. Finally, the totality of available evidence confirms the favorable benefit-risk profile of Medtronic’s internal surgical staplers. Complications are rare, and most are related to inherent risks of the underlying surgical procedure, the patient’s comorbidities, and/or the manner in which the device is used. Medtronic believes that potential risks associated with the use of internal staplers can be mitigated most effectively through appropriate product labeling and training, consistent with Medtronic’s current practices. Medtronic looks forward to working with FDA and other stakeholders on these important initiatives.
EXHIBIT A
MEDTRONIC BRIEFING BOOK
Medtronic’s Submission for the U.S. Food & Drug
Administration General and Plastic Surgery Devices Panel
of the Medical Devices Advisory Committee on Internal
Surgical Stapling Devices
May 30, 2019
TABLE OF CONTENTS
EXECUTIVE SUMMARY ............................................................................................................ 1
DISCUSSION ................................................................................................................................. 4
1. Background .......................................................................................................................... 4
1.1. Clinical Value and Medical Need .................................................................................... 4
1.2. Benefits and Risks of Surgical Staplers ........................................................................... 4
2. Medtronic Internal Surgical Stapling Products .................................................................... 5
2.1. Portfolio Overview ........................................................................................................... 5
2.2. Regulatory History ........................................................................................................... 5
2.3. Pre-Clearance Testing ...................................................................................................... 6
2.4. Quality Systems................................................................................................................ 6
2.5. Risk Mitigation Strategies ................................................................................................ 6
2.5.1. Tissue variability and stapler selection ..................................................................... 7
2.5.2. Design Innovation ..................................................................................................... 7
2.5.3. Product Labeling ....................................................................................................... 8
2.5.4. Physician Training .................................................................................................... 9
3. Safety and Performance of Medtronic’s Surgical Stapling Products ................................. 10
3.1. Medical Device Event Reporting ............................................................................... 10
3.1.1. Medtronic’s Post-Market Vigilance Process ....................................................... 10
3.1.2. Medtronic’s Complaint Reporting Procedures .................................................... 11
3.1.3. FDA’s MAUDE Database ................................................................................... 12
3.1.4. Uses and Limitations of Reportable Event Data ................................................. 12
3.2. Analysis of Medtronic’s Complaint Database ............................................................ 13
3.2.1. Overview of Complaint Data (January 1, 2011 – March 31, 2018) .................... 14
3.2.1.1. All Reportable Complaints .............................................................................. 14
3.2.1.2. Reportable Complaints Involving Death ......................................................... 15
3.2.1.3. Reportable Complaints Involving Serious Injury ............................................ 16
3.2.1.4. Reportable Complaints Involving Device Malfunctions ................................. 17
3.2.2. Detailed Analysis of Reportable Events.............................................................. 17
3.2.2.1. Reportable Complaints Involving Death ......................................................... 18
3.2.2.2. Reportable Complaints Involving Serious Injury ............................................ 18
3.2.2.3. Complaints Involving Device Malfunctions.................................................... 19
3.3. Overview of Studies and Articles Reporting on the Safety of Internal Surgical
Stapling Products ................................................................................................................... 20
3.3.1. Medtronic Sponsored / Funded Studies and Meta-Analyses .............................. 20
3.3.2. Independent Meta-Analyses ................................................................................ 20
3.3.3. Summary of Articles Cited in FDA’s Proposed Order ....................................... 22
3.3.3.1. Prospective Controlled Studies ........................................................................ 22
3.3.3.2. Case Series / Case Reports / Retrospective Analyses ...................................... 22
3.4. Conclusions ................................................................................................................ 22
4. Enhancing Safe Use of Internal Surgical Stapling Devices ............................................... 22
4.1. Classification of Internal Surgical Stapling Devices .................................................. 23
4.2. Proposed Special Controls .......................................................................................... 23
4.3. Proposed Labeling ...................................................................................................... 25
APPENDIX ................................................................................................................................... 26
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EXECUTIVE SUMMARY
Medtronic submits this briefing document in connection with the May 30, 2019 advisory
committee meeting to consider reclassification of internal surgical staplers as Class II devices.
Internal surgical staplers are revolutionary devices that have transformed the surgical
experience for surgeons and patients, and have become the standard of care for many surgical
procedures. Surgical stapling devices have been shown to decrease operative time (reducing
patient exposure to general anesthetics), simplify and standardize surgical techniques, reduce the
inherent variability of hand sutured constructs, and enable more complex surgical procedures. As
FDA has observed, surgical staplers offer other important benefits, including “minimal tissue
reaction, low risk of infection, [and] strong wound closure.”1
Each year, millions of Americans undergo surgical procedures to address a wide variety of
medical problems, ranging from relatively minor health issues to life-threatening emergencies. In
2014, for example, there were more than 300,000 colorectal resections, 440,000 appendectomies,
950,000 cholecystectomies, 900,000 gastrointestinal surgeries, and more than 1 million
cardiothoracic surgeries performed in the U.S.2 Internal surgical staplers are relied on each day
by surgeons to perform these and many other surgeries. Globally, it is estimated that there are
about six million surgical procedures performed each year during which internal staplers may be
used.
Prior to marketing, Medtronic conducts comprehensive testing on its internal surgical
stapling products. Consistent with FDA’s proposed guidance, Medtronic’s current pre-clearance
protocol for internal surgical stapling devices includes testing for: (1) stability, (2)
sterilization/sterility assurance, (3) biocompatibility, (4) safety and performance in vivo, in vitro,
ex vivo; and (5) human factors/usability. For specific products, and as appropriate, Medtronic
performs additional testing, including reprocessing validation, additional bench testing, software
validation and verification, and electrical safety testing.
After these devices come to market, Medtronic monitors their performance and safety
through a robust quality system, which includes advanced design and manufacturing controls, and
a comprehensive post-market vigilance program. As part of this process, Medtronic collects,
evaluates, investigates, and reports customer complaints to FDA, in accordance with the Agency’s
regulations and guidelines. From 2001 to 2017, Medtronic took part in FDA’s alternative
summary reporting (“ASR”) program for its internal surgical stapling products. During this time,
on a quarterly basis, Medtronic submitted to FDA summary information on reportable malfunction
complaints that did not involve an allegation of death or serious injury. In 2017, in conjunction
with a transition from legacy Covidien to Medtronic complaint handling software, the Company
stopped using ASRs for internal stapling products, and resumed submitting individual medical
device reports (“MDRs”) for all reportable malfunction complaints. Throughout this time,
1 FDA, Surgical Staplers and Staples (Mar. 1, 2019), https://www.fda.gov/medical-devices/general-hospital-
devices-and-supplies/surgical-staplers-and-staples. 2 Steiner, C. et al., Surgeries in Hospital-Based Ambulatory Surgery and Hospital Inpatient Settings, 2014,
HCUP Statistical Brief #223 (last updated February 2018) at 10-11 https://www.hcup-
us.ahrq.gov/reports/statbriefs/sb223-Ambulatory-Inpatient-Surgeries-2014.pdf.
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reportable complaints involving death and serious injury were submitted to FDA as individual
MDRs.
The safety profile of Medtronic’s internal surgical stapling products has been established
through decades of real-world use and study. Complications are infrequent and in many cases are
related to inherent risks associated with the underlying surgical procedures or to the manner in
which the device is used by medical professionals. Numerous controlled studies, including some
of the studies cited in FDA’s draft reclassification guidance, support the favorable benefit-risk
profile of internal surgical stapling devices.
In its Letter to Health Care Providers, FDA reported that, during the period between
January 1, 2011 and March 31, 2018, there was a total of more than 41,000 complaints worldwide
related to the use of internal surgical stapling devices, including those manufactured by Medtronic.
In order to put its own numbers into context, Medtronic conducted a detailed analysis of its
complaint database and calculated complaint reporting rates against total sales of its internal
surgical stapling “firing” units. The results showed that complaint rates for Medtronic internal
surgical stapling products have been, and continue to be, very low, averaging below 0.10%. Rates
for reported customer complaints involving death and serious injury are even lower—0.0005%
and 0.0089%, respectively—consistent with expected complication rates associated with surgical
procedures and general anesthesia. In fact, over this period, the rates for reported complaints
involving serious injury decreased by nearly 50%. It is important to emphasize that these rates are
based on complaints received by Medtronic, not on confirmed events of device malfunction,
patient injury, or death.
It is also important to emphasize that the safe use of internal surgical stapling devices
depends on appropriate training and the use of good clinical judgement. As underscored by the
studies cited in FDA’s proposed reclassification order, complications are most common when
surgeons are attempting new and/or more complex procedures, and complication rates decrease
with experience and repetition. Medtronic has implemented a variety of strategies to help reduce
potential complications and to help surgeons safely use its stapling devices. These include
providing appropriate information and instructions in the product labeling, introducing innovative
products that make stapling easier and more consistent, and offering training programs for
physicians and operating room staff.
While Medtronic is confident that these strategies have been effective, the Company also
supports FDA’s efforts to further enhance the safe use of all internal surgical stapling devices. In
particular, Medtronic supports FDA’s proposal to reclassify all internal surgical stapling products
as Class II medical devices, a regulatory approach that is consistent with Medtronic’s own practice.
As discussed below, Medtronic’s internal surgical stapling devices marketed in the United States
have been developed, tested, manufactured, submitted for clearance, and labeled consistent with
FDA’s regulations and requirements for Class II devices. Medtronic also welcomes the
opportunity to work with FDA to develop consistent, reasonable, and appropriate controls and
labeling for all internal surgical stapling products.
Additional background, information, data, and analyses are included in the body of this
document and in the attached appendices. Section 1 provides a brief overview of internal surgical
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stapling devices, their medical uses, and their benefit-risk profile. Section 2 offers background on
Medtronic’s internal stapling portfolio, regulatory history, pre-clearance testing, and risk
mitigation strategies, including design innovation, product labeling and physician training.
Section 3 contains a comprehensive review of the safety data for Medtronic’s internal stapling
devices. Finally, Section 4, describes Medtronic’s position on key aspects of FDA’s draft
reclassification order and proposed labeling guidance.
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DISCUSSION
1. Background
Internal surgical staplers are used to perform tissue resections, vascular transections, and
bowel anastomoses in a wide range of surgical procedures, including bariatric, thoracic, and
colorectal surgery. Surgical staplers have been available in the United States since the late 1960s,
when they were first introduced by United States Surgical Corporation, a predecessor of Covidien
and subsequently Medtronic.3 Over the past five decades, stapling technology has advanced
significantly, offering a range of features and functionalities to enable minimally invasive
techniques and to assist physicians in performing consistent, effective, and reliable internal tissue
repairs. Surgical staplers have a strong benefit-risk profile that is confirmed by decades of clinical
experience and peer-reviewed literature.
1.1. Clinical Value and Medical Need
Each year, millions of Americans undergo surgical procedures to address a wide variety of
medical problems. Before surgical staplers, sutures were the primary method of securing tissues
during these procedures. While effective, suturing has its limitations. Because it is done by hand,
suturing can be time consuming and in certain circumstances technically difficult. Further, the
quality and consistency of a sutured anastomosis—i.e., the proximity of the tissue and the
consistency of the suture line—can vary dramatically depending on the skill and experience of the
surgeon and the type of suturing material used. In the 1960s, the introduction of internal surgical
stapling devices provided a faster, more reliable, and more consistent alternative to suturing and
became the de facto standard of care.
Over the last 50 years, the field has seen significant innovation. The introduction of
endoscopic staplers in the 1990s was a particularly significant milestone, expanding the range of
minimally invasive surgical techniques. These techniques are associated with reduced post-
operative pain, shorter hospital stays, fewer wound complications, and improved cosmetic
appearance compared to open surgery.4
1.2. Benefits and Risks of Surgical Staplers
Internal surgical stapling devices have been shown to decrease operative time (reducing
patient exposure to general anesthesia), simplify and standardize surgical techniques, reduce the
inherent variability of hand sutured constructs, and enable more complex surgical procedures to
be performed. As FDA has observed, surgical staplers offer other important benefits, including
3 Tyco International acquired United States Surgical Corporation into its healthcare business in 1998. Tyco
International spun off its healthcare business in 2007. The new company was called Covidien. Covidien was
acquired by Medtronic in 2014. Throughout this brief, we refer to specific products by the name of their
manufacturer and the overall product line under the Medtronic name. 4 Jaschinski, T. et al., Laparoscopic versus Open Surgery for Suspected Appendicitis, COCHRANE DAT SYST REV
2018;11:CD001546 at 2.
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“[m]inimal tissue reaction, [l]ow risk of infection, [and] [s]trong wound closure.”5 Surgical
staplers also have ancillary benefits, such as reducing surgeon fatigue and lowering the risk of
personal contamination from a needle stick.
Risks associated with surgical staplers include seroma/hematoma;
bleeding/hemorrhage/anastomotic leak; fistula; infection, which may include intraabdominal
abscesses/sepsis; ischemia; chronic pain; allergic reactions; inflammatory reaction; visceral
adhesions; nerve entrapment; tissue erosion; small bowel perforation; potential for stricture;
potential for delayed gastric emptying; and the need for future re-operation. Many of these risks
are related to the underlying surgical procedure, and their likelihood depends on the type of
procedure, the surgical technique, the surgeon’s level of experience, and the patient’s age and
overall health status.
2. Medtronic Internal Surgical Stapling Products
A variety of surgical stapling products are needed to provide surgeons with a full range of
performance and functional options. Medtronic has a portfolio of surgical stapling products that
address a wide range of surgical needs and indications. Medtronic has sought clearance for these
products through FDA’s 510(k) pathway, applied robust quality systems to their design and
manufacture, communicated important risk information through product labeling, offered training
to healthcare providers, and implemented a comprehensive post-market vigilance program.
2.1. Portfolio Overview
In the United States, Medtronic markets 23 internal surgical stapling systems. These
products include manual and powered staplers, linear and circular devices, and open and
endoscopic products, all with a range of staples that are designed for use on tissues of different
types and thickness. The portfolio also includes a number of innovative designs and features
intended to further enhance the safe use of surgical staplers, including software-assisted stapling
handles, articulating stapler reloads, and endoscopic reloads with Tri-Staple™ technology.
2.2. Regulatory History
Since 1988, FDA has classified staplers as Class I devices, under the broader category of
“manual surgical instruments for general use.”6 Class I devices are subject to “General Controls”
and typically are exempt from 510(k) premarket notification requirements.7 FDA separately has
classified “implantable staples” as Class II devices.8 Class II devices generally are subject to
510(k) clearance and may be subject to “Specials Controls.”9
5 FDA, Surgical Staplers and Staples (Mar. 1, 2019), https://www.fda.gov/medical-devices/general-hospital-
devices-and-supplies/surgical-staplers-and-staples. 6 53 Fed. Reg. 23856, 23876 (June 24, 1988) (adding the new regulation, 21 C.F.R § 878.4800 (Manual surgical
instrument for general use)). 7 21 U.S.C. §§ 360(k),(l), 360c(a)(1), (f), (i). 8 21 C.F.R. § 878.4750 (1989) (Implantable staple). (a) Identification. An implantable staple is a staple-like
device intended to connect internal tissues to aid healing. It is not absorbable. (b) Classification. Class II. 9 21 U.S.C. § 360(k), 360c(a)(1)(B).
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Despite the historical difference in classification, Medtronic has treated both its internal
surgical staplers and staples as Class II medical devices. Medtronic has done this because it
considers the “stapler” and the “staple” to constitute a single surgical system. Accordingly,
Medtronic has conducted pre-clearance testing, submitted 510(k) applications, and obtained
clearance for its currently marketed internal surgical stapling products.
Appendix 1 provides a 510(k) clearance history for Medtronic internal surgical stapling
products currently marketed in the U.S.
2.3. Pre-Clearance Testing
Medtronic conducts comprehensive testing on its internal surgical stapling
products. While the specific protocol may vary to some extent from device to device, consistent
with FDA’s proposed guidance, Medtronic’s current pre-clearance evaluation for internal surgical
stapling devices includes testing for: (1) stability, (2) sterilization/sterility assurance, (3)
biocompatibility, (4) safety and performance in vivo, in vitro, ex vivo; and (5) human
factors/usability. For specific products, and as appropriate, additional testing is performed,
including reprocessing validation, additional bench testing, software validation and verification,
and electrical safety testing.
2.4. Quality Systems
Medtronic’s quality system is designed to ensure that its internal surgical stapling products
fully meet design and performance specifications before they are approved for distribution on the
market and ultimately are delivered to our customers. Medtronic applies in-process and pre-
release testing and monitoring to detect potential problems in manufacturing. Medtronic also has
a robust post-market vigilance process for products in the field, staffed by trained personnel,
including engineers and medical professionals, who receive information about devices (including
their quality and performance) and promptly investigate and evaluate potential problems.
Medtronic’s design control process has implemented Design for Six Sigma strategies that
continuously are enhanced and refined to ensure that customer requirements are translated into
both design inputs and outputs. Design verification is conducted against boundary conditions to
represent real world use (including foreseeable misuse). Design validation incorporates Usability
& Human Factors strategies to ensure that the Instructions for Use and design specifications satisfy
the intended use requirements.
Where appropriate, Medtronic utilizes automated manufacturing equipment for state-of-
the-art assembly and inspection, and to reduce process variability and dependency on manual
assembly. These processes are validated to assure consistent process output and are monitored for
continuous improvement opportunities.
2.5. Risk Mitigation Strategies
Use of internal surgical stapling devices is associated with some risks, most of which relate
to inherent tissue variability, the underlying surgical procedure, and the condition of the patient.
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Medtronic’s product labeling, design innovations, and training programs are designed to mitigate
these potential risks and to enhance the safe use of its internal surgical stapling products.
2.5.1. Tissue variability and stapler selection
Surgical staplers are designed to function best when used on tissue of the appropriate
thickness (“indicated tissue”) and in the appropriate surgical setting. When staplers are used on
over-indicated tissue (i.e., tissue that is above the indicated range of thickness), the additional
stress on the device can, on occasion, lead to staple malformation, problems with staple line
integrity, or shearing damage to tissues adjacent to the staple line. Conversely, using staplers on
under-indicated tissue (tissue that is below the indicated range of thickness) can damage the tissue
and cause staple line leaks and bleeds.10 Surgeons are trained on surgical stapler use and selection
in their residency programs. While surgeons generally know which tissue types are thicker or
thinner, thickness can vary between patients and within a single organ. Assessing tissue thickness
and condition requires clinical judgment in the operating room on a patient-by-patient basis.
During surgery, surgeons can take steps to ensure the integrity of the staple line. For thin
or friable tissues, buttressing materials can be used to provide a thicker base for anchoring
staples.11 For thicker tissues, larger staples may be used to allow closure within an acceptable
force range. Firing slowly, particularly in thicker tissues, leads to better staple line formation.12
Suture reinforcement of a staple line and the use of fibrin sealants also may help, although the
event rates are so low (<1%) that it is difficult to demonstrate a significant effect.13 Upon finishing
a tissue approximation or anastomosis, surgeons further reduce post-operative complications by
checking the integrity of the staple line. These all are standards of good surgical practice, which
Medtronic reinforces in product labeling and in its training programs.
Medtronic provides indicated tissue ranges for each staple size in its labeling. Medtronic
tests staples within the indicated range for proper staple formation and closure. Medtronic further
tests its staples beyond the indicated range for functional closure (that is, where there is foreseeable
misuse on non-indicated tissue thickness, staple formation may be impacted but the staple line
retains integrity). Medtronic also color codes its staple cartridges to make identification and
selection of appropriate staple sizes easier in the operating room.
2.5.2. Design Innovation
Medtronic has introduced a number of innovative surgical stapling products intended to
make surgical stapling simpler, safer, and more consistent. These new products build on
10 Chekan, E. et al, Surgical Stapling Device-Tissue Interactions: What Surgeons Need To Know To Improve
Patient Outcomes, MED DEV (AUCKL) 2014;7:305-18 at 309. 11 Choi, Y. et al., Reinforcing the Staple Line During Laparoscopic Sleeve Gastrectomy: Does it Have
Advantages? A Meta-Analysis, OBES SURG 2012;22:1206-13 at 1210-11; Daskalakis M. et al., Impact Of
Surgeon Experience And Buttress Material On Postoperative Complications After Laparoscopic Sleeve
Gastrectomy, SURG ENDOSC 2011;25:88-97 at 96. 12 Hasegawa, S. et al., Effect of Tri-Staple™ Technology and Slow Firing on Secure Stapling Using and
Endoscopic Linear Stapler, DIG SURG 2015;32:353-60 at 355. 13 Sajid, M. et al., Use Of Staple-Line Reinforcement In Laparoscopic Gastric Bypass Surgery: A Meta-Analysis,
SURG ENDOSC 2011;25:2884-91 at 2884.
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established and tested technology, while introducing new functional and design features. For
example, in 2010, Medtronic introduced reloads with Tri-Staple™ technology, which help create
a strong staple line while preserving tissue perfusion and reducing tissue damage. In 2012,
Medtronic introduced iDrive™ staplers and, in 2017, Signia™ staplers. These software-assisted
staplers actively measure force feedback during staple deployment, adapt stapling speed, and help
surgeons achieve a consistent and effective stapling line. Recently, Medtronic also introduced a
new staple reload with a built-in microchip that allows the Signia™ stapler to identify the reload
cartridge and ensure that it has not been previously fired.
2.5.3. Product Labeling
The product labeling for Medtronic’s internal surgical staplers and reloads includes
detailed, device-specific information on appropriate use and staple selection, as well as relevant
contraindications, warnings, and precautions. Attached as Appendix 2 are copies of the user
manual for Medtronic’s Signia™ Stapling System and the product labeling for its Tri-Staple™
Reloads. Examples of categories of information provided in the product labeling are listed in
Table 2.1 below.
Table 2.1: Examples of Information in Signia™ Stapling System User Manual and Tri-
Staple™ Reload Labeling and Instructions for Use
Device Compatibility
The Signia™ Stapling System is “compatible with Endo GIA™
single-use reloads and Endo GIA™ single-use reloads with Tri-
Staple™ Technology.”
Tissue Thickness
“Do not use the Tri-Staple™ 2.0 reload or Tri-Staple™ 2.0 curved
tip reload extra thin/vascular (gray) on any tissue that compresses
to less than 0.75 mm in thickness, on any tissue that cannot
comfortably compress to 1.0 mm or on the aorta.”
“The stapler does not directly sense tissue thickness. Select the
stapling reload with an indicated tissue range that is appropriate
for the target tissue. Overly thick or thin tissue may result in
unacceptable staple formation.”
Tissue Condition
Do not use “on ischemic or necrotic tissue” or “on friable or
delicate tissue and/or where the closure of the device might be
destructive.”
Proper Use of the Device
“Ensure tissue has not extended (extruded) beyond the tissue stop
proximally. Tissue forced into the instrument beyond the tissue
stop may be transected without stapling.”
“[E]nsure that no obstructions, such as clips, are incorporated into
the instrument jaws. Firing over an obstruction may result in
incomplete cutting action and/or improperly formed staples.”
“Do not apply excessive force to the introducer, excessive force
may separate it from the anvil.”
Hemostasis
The stapler should not be used “where adequacy of hemostasis
cannot be verified” or “without making provisions for proximal
and distal [vessel] control.”
9 | P a g e
“Inspect the staple line and the surrounding site for hemostasis
and/or leakage. Minor bleeding or leakage may be controlled by
electrocautery or sutures.”
Adverse Reactions “[S]eroma/hematoma; bleeding/hemorrhage/anastomotic leak;
fistula; infection, which may include intraabdominal
abscesses/sepsis; ischemia; chronic pain; allergic reactions;
inflammatory reaction; visceral adhesions; nerve entrapment;
tissue erosion; small bowel perforation; potential for stricture;
potential for delayed gastric emptying, and the need for future re-
operation.”
2.5.4. Physician Training
Medtronic also provides training and resources to physicians, consistent with industry best
practices, and principles expressed in the AdvaMed Code.14 These include:
Medtronic provides training to surgeons and first-assistant nurses at hospitals through our
network of 600 onsite representatives. When new products are introduced, Medtronic
representatives offer in-service to healthcare professionals on the new products and may
attend initial cases to provide technical support as the healthcare professionals gain
knowledge and experience with the device.
Medtronic also has a PACE (Professional Affairs & Clinical Education) program that helps
provide further training for surgeons and staff. Medtronic training faculty consists of
nationally known experts in their fields (typically from academic institutions), who provide
peer-to-peer, physician-led training. Training sessions often are 1-2 full days, which
include observation of surgical procedures. For trainees seeking skill development,
Medtronic offers didactic lectures and surgical simulations (cadaver or animal) using
Medtronic stapling technology. For trainees seeking advanced technique development, the
program involves case observation of the instructing physician. The program addresses
staple selection and tissue thickness considerations. Over the last six years, more than
2,000 surgeons have participated in the program. Appendix 3 includes the agenda from
an Advanced Minimally Invasive Colorectal Techniques Masterclass offered by Medtronic
in March 2019.
Medtronic supports fellowship programs and medical society training programs, such as
the Society of American Gastrointestinal and Endoscopic Surgeons (“SAGES”), through
grants. Medtronic also supports the Institut de Recherche contre le Cancer de l’Appareil
Digestif (“IRCAD”), an international organization focused on minimally invasive surgical
training. In 2018, IRCAD trained more than 8,000 surgeons globally.
14 AdvaMed, Code of Ethics on Interactions with U.S. Health Care Professional (effective Jan. 1, 2020) at 2,
https://www.advamed.org/sites/default/files/resource/advamed_u.s._code_of_ethics_final_-
_eff._jan_1_2020.pdf (“Medical Technology . . . often consists of complex tools, devices, and technology
requiring highly dependent ‘hands on’ interactions with Health Care Professionals from beginning to end.”).
10 | P a g e
Since 2009, Medtronic has partnered with Pfeidler, a subsidiary of the Association of
perioperative Registered Nurses, to deliver an accredited online continuing education
program, “Best Practices on Surgical Stapling,” to nurses and surgical technologists. Over
the last six months, nearly 500 health care professionals have completed this program.
3. Safety and Performance of Medtronic’s Surgical Stapling Products
3.1. Medical Device Event Reporting
3.1.1. Medtronic’s Post-Market Vigilance Process
Medtronic has a post-market vigilance process that includes collection, evaluation,
investigation, and reporting of customer complaints to FDA. FDA defines a “complaint” as “any
written, electronic, or oral communication that alleges deficiencies related to the identity, quality,
durability, reliability, safety, effectiveness, or performance of a device after it is released for
distribution.”15 Medtronic’s policies and procedures interpret this definition broadly so as to
ensure that information that potentially meets FDA’s criteria is received as a complaint and is fully
investigated. Allegations of device association to malfunctions, serious injury, or death are
reported per FDA regulations as a Medical Device Report (“MDR”).
Complaints come to Medtronic from many different sources, including healthcare
providers, field personnel, patients, family members, and lawyers. Additional sources of
complaints, which Medtronic actively pursues, include medical literature and patient registries.
These complaints vary widely in terms of their substance and the amount of information that is
provided and/or available. Complaints can involve relatively minor issues (e.g., the packaging
was damaged prior to delivery) or raise more serious concerns (e.g., the patient was injured).
Regardless of their nature and severity, complaints related to Medtronic’s internal surgical
staplers are thoroughly investigated. For reportable complaints, Medtronic utilizes a cross-
functional approach to investigations, which may include medical professionals, scientists,
engineers, and other technical experts (on an as-needed basis). Medtronic works to: (1) collect
and analyze available information regarding the reported issue; (2) conduct an investigation on the
product and its manufacturing history (when deemed appropriate); (3) review complaint history
and other relevant data; and, (4) when available, perform testing on the actual device involved.
The ultimate goal of the investigation is to determine the root cause of the alleged problem, to
identify any potential safety or performance issues, and, when appropriate, to implement corrective
action to mitigate and prevent re-occurrence.
In addition, medical safety experts conduct an independent, parallel investigation of
reportable complaints involving death or serious injury. This investigation is aimed at determining
whether the device could have played a role in the death or alleged injury. The result of this
investigation helps guide further action, but does not alter Medtronic’s initial reporting to FDA
and other regulatory agencies.
15 21 C.F.R. § 820.3.
11 | P a g e
If potential issues are identified through either the complaint handling or the medical safety
review process, Medtronic evaluates those issues and, when appropriate, promptly takes corrective
action. The fact that a Complaint is submitted to Medtronic, or reported as an MDR to FDA, does
not mean, and should not be interpreted to mean, that a device malfunctioned or that a device
caused injury to a patient.16
3.1.2. Medtronic’s Complaint Reporting Procedures
Medtronic and other manufacturers of medical devices are required to report to FDA any
event or complaint that “reasonably suggests” that one of their marketed devices: (1) “may have
caused or contributed to a death or serious injury” or (2) “[h]as malfunctioned and that the device
or a similar device marketed by the manufacturer would be likely to cause or contribute to a death
or serious injury if the malfunction were to recur.”17 Under FDA’s standard reporting pathway,
events that meet these criteria (“MDR reportable events”) must be individually reported within 30
calendar days after the manufacturer becomes aware of them (unless they meet the criteria for 5-
day reports).18 Medtronic has, and continues to, provide FDA the required information on
reportable complaints involving Medtronic’s internal surgical stapling products, including
reportable events involving death, serious injury and device malfunctions as defined by FDA
regulations.
In 1997, FDA created an alternative summary reporting program (“ASR”) pursuant to
authority under 21 C.F.R § 803.19, which allowed medical device manufacturers to request
authorization to submit certain types of complaints in a summary document submitted to FDA on
a quarterly basis.19 As Larry Kessler, former director of FDA’s Center for Devices and Radiologic
Health’s (“CDRH”) Office of Surveillance and Biometrics, explained, the ASR program offered
several advantages, including allowing FDA to conserve its resources for reviewing reports related
to products whose safety have not yet been well-characterized and providing manufacturers more
time to follow up and fully evaluate event reports.20 FDA issued final guidance on the ASR process
in October 2000.21
In 2001, FDA invited Medtronic to apply for the ASR program, and, the same year, the
Company received authorization to use the ASR pathway for its surgical stapling products
(attached as Appendix 4). Importantly, the ASR authorization applied only to customer
complaints involving alleged device malfunction. It did not cover complaints reporting death
or other serious injuries. Medtronic’s process always has been to submit death and serious injury
complaints to FDA on individual MDRs.
From 2001 to mid-2017, Medtronic submitted ASRs to FDA on a quarterly basis for
complaints that met the definition of a reportable malfunction. In 2017, in conjunction with a
16 See 21 C.F.R. § 803.16. 17 21 C.F.R. § 803.3(o)(2). 18 21 C.F.R. § 803.10(c). 19 See MED DEVICE ONLINE, CDRH Guidance Details Alternative Summary Reporting of Adverse Events (Dec. 11,
2000), https://www.meddeviceonline.com/doc/cdrh-guidance-details-alternative-summary-rep-0001. 20 Id. 21 FDA, Guidance, Medical Device Reporting – Alternative Summary Reporting (ASR) Program (Oct. 19, 2000),
https://www.fda.gov/media/71256/download.
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transition from legacy Covidien to Medtronic complaint handling software, the Company stopped
using ASRs for internal stapling products, and resumed submitting individual MDRs for all
reportable malfunction complaints.
3.1.3. FDA’s MAUDE Database
FDA maintains a searchable, public database of event reports involving medical devices,
known as the Manufacturer and User Facility Device Experience Database (“MAUDE”). The
Agency has sole control over the content of the MAUDE database. According to FDA, the
database currently contains “voluntary reports since June 1993, user facility reports since 1991,
distributor reports since 1993, and manufacturer reports since August 1996.”22 FDA has not
included events reported through ASR in the database.23 However, FDA always has had
information reported in ASRs available for purposes of monitoring the post-market safety and
performance of Medtronic’s internal surgical stapling devices.
3.1.4. Uses and Limitations of Reportable Event Data
FDA, Medtronic, and other manufacturers use reportable event data as one method to
identify potential safety and performance signals for medical devices. Medtronic uses statistical
algorithms to monitor trends in complaint reporting and identify potential signals. When signals
are identified, the information is escalated for further evaluation, which typically includes a review
of available evidence and an investigation. When appropriate, corrective action is taken.
FDA also performs analyses using MAUDE data to identify emerging signals. While
MAUDE data serves an important signal detection function, it “is not intended to be used either to
evaluate rates of adverse events or to compare adverse event occurrence rates across devices.”24
That is because, as FDA has explained: (1) there is no certainty that the reported event was due to
the product; (2) reports frequently do not contain enough detail to properly evaluate the event; (3)
many factors can influence whether an event will be reported, such as the time a product has been
marketed and publicity about an event; (4) duplicate reports frequently are submitted for the same
event; and (5) MDR data alone cannot be used to establish rates of events, evaluate a change in
event rates over time, or compare event rates between devices; and (6) confirming whether a device
actually caused a specific event can be difficult based solely on information provided in a given
report.25 Establishing a cause-and-effect relationship is especially difficult if circumstances
surrounding the event have not been verified, or if the device in question has not been directly
22 FDA, Manufacturer and User Facility Device Experience Database - (MAUDE) (May 15, 2019),
https://www.fda.gov/medical-devices/mandatory-reporting-requirements-manufacturers-importers-and-device-
user-facilities/manufacturer-and-user-facility-device-experience-database-maude. 23 FDA, Medical Device Reporting (MDR): How to Report Medical Device Problems (May 2, 2019),
https://www.fda.gov/medical-devices/medical-device-safety/medical-device-reporting-mdr-how-report-
medical-device-problems. 24 FDA, Manufacturer and User Facility Device Experience Database - (MAUDE) (May 15, 2019),
https://www.fda.gov/medical-devices/mandatory-reporting-requirements-manufacturers-importers-and-device-
user-facilities/manufacturer-and-user-facility-device-experience-database-maude. 25 FDA, Questions and Answers on FDA's Adverse Event Reporting System (FAERS) (Jun 4, 2018),
https://www.fda.gov/drugs/surveillance/fda-adverse-event-reporting-system-faers
13 | P a g e
evaluated.26
Because many internal surgical stapling devices incorporate multiple components and/or
accessories, consistent with FDA guidance, Medtronic frequently reports complaints involving
surgical stapling products under more than one product code for a single reported event.27 For
example, two MDR reports may be submitted for a single complaint where the design includes
both a stapler handle and the stapler reload. As a result, numerous duplicate reports exist in the
MAUDE database for Medtronic’s internal surgical stapling products. Table 3.1 provides a
comparison of the number of MDRs submitted by Medtronic against the actual number of unique
death and serious injury complaints received in 2017 and 2018.
Table 3.1: Number of Reported MDRs versus Number of Complaints Received, 2017-2018
Year
Complaints Involving Death Complaints Involving Serious Injury
# of MDRs
Reported to FDA
# of Unique
Reportable Events
# of MDRs
Reported to FDA
# of Unique
Reportable Events
2017
27
16
1,150
674
2018
40
21
1,293
734
Finally, the absolute number of events reported for a particular device does not describe
the device’s relative performance or safety. Absent a denominator—i.e., how often the device is
used in clinical practice—it is impossible to assess how frequently the reported event occurred.
Moreover, within MAUDE, it is often impossible to deduce whether the event is related to the
device, or whether it is the result of confounding factors, such as intrinsic risks associated with the
procedure in which the device was used (e.g., a complex surgical procedure during which a surgical
stapler was used).
3.2. Analysis of Medtronic’s Complaint Database
Medtronic performed a detailed analysis of its global Complaint database, which includes
complaints received worldwide for its surgical stapling devices. The analysis demonstrates that
rates of reportable events have been low and stable over the past seven years, with a significant
decline in serious injury reports over this same period.
In performing the analysis, Medtronic selected the period between January 1, 2011 and
March 31, 2018, to match the dates referenced in FDA’s March 8, 2019 news release.28
26 Id. 27 FDA, Guidance, Medical Device Reporting for Manufacturers (Nov. 8, 2016), at 8,
https://www.fda.gov/media/86420/download. 28 FDA, News Release, FDA Takes Steps to Help Reduce Risks Associated with Surgical Staplers and Implantable
Staples (Mar. 8, 2019), https://www.fda.gov/news-events/press-announcements/fda-takes-steps-help-reduce-
risks-associated-surgical-staplers-and-implantable-staples.
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Additionally, for figures showing rates over time, Medtronic included complaints up to March 31,
2019 to show more recent performance. To enhance the accuracy of the analysis, Medtronic
excluded any duplicate reports that could be identified based on internal data. Further, in order to
provide a context for the absolute number of reports, Medtronic calculated an annual reporting rate
against the total sales of its surgical stapling firing units during the relevant time period. For events
involving reported death and/or serious injury, Medtronic compared those rates to expected rates
of similar events in the general population of patients undergoing surgical procedures in the United
States (where possible). It is important to emphasize that the rates reported in this analysis are
based on complaints received by Medtronic, not on confirmed events of device malfunction,
patient injury, or death.
3.2.1. Overview of Complaint Data (January 1, 2011 – March 31, 2018)
3.2.1.1. All Reportable Complaints
In the period between January 1, 2011 and March 31, 2018, the overall reportable
complaint rate for Medtronic internal surgical stapling devices (complaints over sales, as described
above) was relatively stable, ranging from 0.06% to 0.10%. There were a total of 38,322 reportable
complaints involving Medtronic’s surgical stapling products, including complaints reported
through both the MDR (12,999) and ASR (25,323) pathways.29
Figure 3.1: Reported Rates over Time, All Reportable Complaints, Regardless of
Relationship to Stapling Device
29 It should be noted that our analysis of the data contained in FDA’s March 8, 2019 news release appears to
exclude reportable malfunctions submitted by manufacturers via the ASR pathway.
0.00%
0.01%
0.02%
0.03%
0.04%
0.05%
0.06%
0.07%
0.08%
0.09%
0.10%
0
1000
2000
3000
4000
5000
6000
7000
2011 2012 2013 2014 2015 2016 2017 2018 2019
Rep
ort
able
Eve
nt
Rat
e
Rep
ort
able
Eve
nts
Year
Reportable Events by Event Type
Death - Reportable Malfunction - Reportable Serious Injury - Reportable rates
15 | P a g e
3.2.1.2. Reportable Complaints Involving Death
In the period between January 1, 2011 and March 31, 2018, the reported rate for events
involving death (complaints over sales) was relatively stable, ranging from 0.0002% to 0.0005%.
During this period, Medtronic submitted a total of 159 MDRs, representing 145 unique complaints,
involving the death of a patient who had a procedure during which Medtronic’s surgical stapling
products reportedly were used. These events were reported through the traditional reporting
pathway as individual MDRs, not through the ASR pathway.
Even accounting for events that may not have been reported to Medtronic
(“underreporting”), the observed event rate was well below the reported mortality rate in the
general population of patients undergoing surgery in the United States, which is estimated to be
about 0.2-0.5% for elective procedures and about 1-2% for emergency and complex surgeries.30
Figure 3.2: Reported Rates over Time, All Reportable Complaints Involving Death,
Regardless of Relationship to Stapling Device
30 Healey, M. et al., Complications in Surgical Patients, ARCH SURG 2002;137(5):611-18 at 611; Heeney, A. et
al., Surgical Mortality - An Analysis of All Deaths Within a General Surgical Department, SURGEON
2014;12(3):121-28 at 121; Ingraham, A. et al., Comparison of Hospital Performance in Emergency Versus
Elective General Surgery Operations at 198 Hospitals, J AM COLL SURG 2011;212:20-28 at 20; Tevis, S. et al.,
Postoperative Complications And Implications On Patient-Centered Outcomes, J SURG RES 2013;181(1):106-
13; Weiser, T. et al., Excess Surgical Mortality: Strategies for Improving Quality of Care, in ESSENTIAL
SURGERY 279-305 at 279-80, 283 (3d ed. 2015).
0.0000%
0.0001%
0.0001%
0.0002%
0.0002%
0.0003%
0.0003%
0.0004%
0.0004%
0
5
10
15
20
25
30
2011 2012 2013 2014 2015 2016 2017 2018 2019
Even
t R
ate
Even
t C
ou
nt
Year
Reportable Events - Death
Death - Reportable Rate
16 | P a g e
3.2.1.3. Reportable Complaints Involving Serious Injury
In the period between January 1, 2011 and March 31, 2018, the reported rate for events
involving serious injury31 decreased significantly, from 0.017% to 0.0089%.32 As with events
involving death, the event rate was orders of magnitude below the reported incidence of major
complications in general surgical practice, estimated to be ~5% in elective and ~15% in emergency
procedures.33
Medtronic submitted a total of 5,847 MDRs, representing 5,296 unique complaints,
alleging serious injury in a patient who had a procedure during which a Medtronic surgical stapling
product reportedly was used. These involved a wide range of alleged issues, including use of an
intraoperative x-ray and prolonged operative time. These events were reported as individual
MDRs, not through the ASR pathway.
Figure 3.3: Reported Rates over Time, All Reportable Complaints Involving Serious
Injuries, Regardless of Relationship to Stapling Device
31 A “serious injury” is defined as an injury or illness that is “life threatening;” “[r]esults in permanent impairment
of a body function or permanent damage to a body structure;” or “[n]ecessitates medical or surgical intervention
to preclude permanent impairment of a body function or permanent damage to a body structure.” 21 C.F.R. §
803.3(w). 32 P = 0.03. Based on change-point analysis, with data evaluated in 6 month intervals. 33 Tevis, S. et al. (2013), supra note Error! Bookmark not defined.; Ingraham, A. et al. (2011), supra note
30Error! Bookmark not defined., at 20; Healey, M. et al. (2002), supra note 30, at 614.
0.000%
0.002%
0.004%
0.006%
0.008%
0.010%
0.012%
0.014%
0.016%
0.018%
0
100
200
300
400
500
600
700
800
900
1000
2011 2012 2013 2014 2015 2016 2017 2018 2019
Even
t R
ate
Even
t C
ou
nt
Year
Reportable Events - Serious Injury
Serious Injury - Reportable Rate
17 | P a g e
3.2.1.4. Reportable Complaints Involving Device Malfunctions
A “malfunction” is defined as “the failure of a device to meet its performance specifications
or otherwise perform as intended. Performance specifications include all claims made in the
labeling for the device.”34 A complaint alleging a malfunction does not necessarily mean the
device was defective. As discussed below in Section 3.2.2.3, the majority of such complaints were
not determined by Medtronic to be related to the device.
In the period between January 1, 2011 and March 31, 2018, the reported rate for complaints
alleging malfunction has been relatively stable, ranging from 0.05% to 0.09%. There were a total
of 32,881 reportable complaints alleging malfunction of a Medtronic internal stapling device. All
of these were reported to FDA, either through the traditional or the ASR pathway. None of these
malfunction reports involved death or other injury to a patient.
Figure 3.4: Reported Rates over Time, All Reportable Complaints Involving Serious
Injuries, Regardless of Relationship to Device
3.2.2. Detailed Analysis of Reportable Events
In order to provide further context, Medtronic also conducted a detailed analysis of
reportable events received during the period between January 1, 2018 and March 31, 2019,
focusing on the specific issues raised in FDA’s draft reclassification order. Rates of complaints
considered potentially related to device use were low (death 0.00002%; serious injury 0.0003%;
malfunction 0.011%). The results of the analysis are described below.
34 21 C.F.R. § 803.3(k).
0.0000%
0.0100%
0.0200%
0.0300%
0.0400%
0.0500%
0.0600%
0.0700%
0.0800%
0.0900%
0
1000
2000
3000
4000
5000
6000
2011 2012 2013 2014 2015 2016 2017 2018 2019
Even
t R
ate
Even
t C
ou
nt
Year
Reportable Events - Malfunctions
Malfunction - Reportable Rate
18 | P a g e
3.2.2.1. Reportable Complaints Involving Death
During the period between January 1, 2018 and March 31, 2019, there were 28 reported
events of death occurring in patients who had surgical procedures during which Medtronic staplers
reportedly were used. Of these, two were considered possibly related to use of the device, a
potential complication rate of 0.00002% (possibly related complaints over sales).
3.2.2.2. Reportable Complaints Involving Serious Injury
During the period between January 1, 2018 and March 31, 2019, there were 978 reports of
serious injury occurring in patients who had surgical procedures during which Medtronic staplers
reportedly were used. Of these, 804 involved some form of surgical intervention. Overall, 37
reported events were considered possibly related to use of the device, a potential complication rate
of 0.0003% (possibly related complaints over sales).
Specific information on events identified in FDA’s draft reclassification order are provided
below.
Bleeding. 105 of the 978 reported Serious Injury Events (10.7%) alleged bleeding in
patients who had surgical procedures during which Medtronic stapler(s) reportedly
were used.35 Of these, seven were considered possibly related to use of the device, a
potential complication rate of 0.00006% (possibly related complaints over sales). By
comparison, it is estimated that bleeding occurs in approximately 2% of all surgical
procedures.36
Sepsis. 15 of the 978 reported Serious Injury Events (1.5%) alleged sepsis in patients
who had surgical procedures during which Medtronic stapler(s) reportedly were used.37
Of these, one was considered possibly related to use of the device, a potential
complication rate of 0.00001% (possibly related complaints over sales). By
comparison, it is estimated that post-operative sepsis occurs in approximately 1% of
surgical procedures.38
Fistula Formation. 18 of the 978 reported Serious Injury Events (1.8%) alleged fistula
formation in patients who had surgical procedures during which Medtronic stapler(s)
reportedly were used.39 Of these, two were considered possibly related to use of the
device, a potential complication rate of 0.00002% (possibly related complaints over
sales). By comparison, it is estimated that post-operative fistulas occur in
35 FDA codes defined as Blood Loss, Hemorrhage, or Hemothorax. 36 Kuthe, A. et al., Multicenter prospective evaluation of a new articulating 5-mm endoscopic linear stapler, SURG
ENDOSC 2016;30:1883-93 at 1886. 37 FDA codes defined as Sepsis or Septic Shock. 38 Vogel, T. et al., Postoperative Sepsis in the United States, ANN SURG 2010;252(6);1065-71 at 1065. 39 FDA code defined as Fistula.
19 | P a g e
approximately 5% of abdominal surgical procedures, with much higher rates reported
with certain procedures such as distal pancreatectomy.40
Tearing of Internal Tissues and Organs. 329 of the 978 reported Serious Injury
Events (33.6%) alleged that tearing of internal tissues and organs during surgical
procedures in which Medtronic stapler(s) reportedly were used.41 Of these, 14 were
considered possibly related to use of the device, a potential complication rate of
0.00013% (possibly related complaints over sales).
Cancer Recurrence. None of the reported Serious Injury Events alleged a cancer
event.42
3.2.2.3. Complaints Involving Device Malfunctions
During the period between January 1, 2018 and March 31, 2019, there were 5,907
complaints of alleged device malfunction involving Medtronic internal surgical staplers. This
represents a reporting rate of potential device malfunction of 0.05% (alleged malfunctions over
sales). On investigation, a possible device performance issue was identified in 126 of the 5,907
complaints, a potential malfunction rate of 0.0011% (possible performance issues over sales).
Failure of the Stapler to Fire the Staple. 3,254 of the 5,907 reported Malfunction
Events (55.1%) alleged failure to fire in patients who had surgical procedures during
which Medtronic stapler(s) reportedly were used. Of these, 16 were considered
possibly related to the device, a potential device malfunction rate of 0.00015%
(possibly related events over sales).
Misfiring or Difficulty in Firing. 693 of the 5,907 reported Malfunction Events
(11.7%) alleged misfire in patients who had surgical procedures during which
Medtronic stapler(s) reportedly were used. Of these, six were considered possibly
related to the device, a potential device malfunction rate of 0.00005% (possibly related
events over sales).
Opening of the Staple Line or Malformation of Staples. 663 of the 5,907 reported
Malfunction Events (11.2%) alleged “failure to adhere or bond,” “loss of or failure to
bond,” or “failure to form staple” in patients who had surgical procedures during which
Medtronic stapler(s) reportedly were used. Of these, five were considered possibly
related to the device, a potential device malfunction rate of 0.00005% (possibly related
events over sales).
40 Wercka, J. et al., Epidemiology and Outcome Of Patients With Postoperative Abdominal Fistula, REV COL
BRAS CIR 2016;43(2):117-23 at 120; Falconi, M. et al., The Relevance of Gastrointestinal Fistulae in Clinical
Practice: A Review, GUT 2002;49(Suppl IV):iv2-10 at iv5-6. 41 FDA codes defined as Tissue Damage, Failure to Anastomose, Dehiscence of Organ, Aortic Dissection, or
Laceration(s). 42 FDA code defined as Cancer.
20 | P a g e
Misapplied Staple. 293 of the 5,907 reported Malfunction Events (5.0%) alleged a
human-device interface problem in patients who had surgical procedures during which
Medtronic stapler(s) reportedly were used. Of these, six were considered possibly
related to the device, a potential device malfunction rate of 0.00005% (possibly related
events over sales).
3.3. Overview of Studies and Articles Reporting on the Safety of Internal Surgical
Stapling Products
Numerous controlled studies have reported on the safety of surgical stapling devices.
Below we have provided an overview of data specific to Medtronic stapling products, as well as a
summary of meta-analyses addressing the safety and performance of internal surgical stapling
devices generally. The studies confirm the overall favorable benefit-risk profile of Medtronic’s
internal surgical stapling devices, and the low rates of complication observed in clinical use.
3.3.1. Medtronic Sponsored / Funded Studies and Meta-Analyses
In Medtronic sponsored and/or funded studies and meta-analyses, complication rates with
Medtronic internal surgical stapling devices consistently were low. Rates of events relevant to the
issues raised in FDA’s proposed reclassification order are summarized below.
Device-related mortality: 0%
Post-operative bleeding: 0% – 2.07%
Post-operative leaks: 0% – 5.42%
Pulmonary fistula: 0% - 1.7%
Abdominal fistula: 0% - 12.4% (pancreatic)
Summaries of the studies providing the above data are included in Appendix 5.
3.3.2. Independent Meta-Analyses
A search of peer-reviewed publications on pubmed.gov identified 10 independent meta-
analyses including data on at least 2,000 procedures that reported on the safety of internal surgical
stapling devices as compared to sutures. Overall, complication rates in procedures performed with
internal surgical staplers were similar to, or even lower than, those performed with sutures.
Seven of the analyses, including more than 31,000 procedures, reported on anastomotic
leaks.43 Six found lower rates of anastomotic leaks with surgical staplers compared to
43 Deng, X. et al., Hand-Sewn vs. Linearly Stapled Esophagogastric Anastomosis for Esophageal Cancer: A Meta-
Analysis, WORLD J GASTROENTROL 2015;21(15):4757-64; Gong, J. et al., Stapled vs. Hand Suture Closure of
Loop Ileostomy: A Meta-Analysis, COLORECTAL DIS 2013;15(10):e561-68; Jiang, H. et al., Meta-Analysis of
Hand-Sewn versus Mechanical Gastrojejunal Anastomosis During Laparoscopic Roux-en-Y Gastric Bypass for
Morbid Obesity, INT J SURG 2016;32:150-57; Liu, Q. et al., Is Hand Sewing Comparable with Stapling for
Anastomotic Leakage after Esophagectomy? A Meta-Analysis, WORLD J GASTROENTROL 2014;20(45):17218-
26; Lovegrove, R. et al., A Comparison of Hand-Sewn versus Stapled Ileal Pouch Anal Anastomosis (IPAA)
Following Proctocolectomy: A Meta-Analysis of 4183 Patients, ANN SURG 2006;244(1):18-26; Madani, R. et
21 | P a g e
sutures, although only one of the results was statistically significant.44 One found no
difference between the groups.45
Four analyses, including more than 13,000 procedures, evaluated fistula formation.46
All reported lower rates with staplers than with sutures; two of those were statistically
significant.47
Four analyses, including more than 15,000 procedures, reported on operative time.48
Three reported statistically significantly shorter operative times with staplers than
sutures.49
Four analyses, including more than 14,000 procedures, reported on the incidence of
post-operative small bowel obstruction.50 Three reported statistically significantly
lower rates of small bowel obstruction in procedures where staplers were used.51
Three analyses evaluated reoperation rates.52 Across 5,894 procedures, no significant
difference was observed between staplers and sutures.
Two analyses provided data on post-operative mortality.53 The analyses included more
than 2,200 patients and did not find any significant differences in mortality rates.
One analysis evaluated rates of post-operative bleeding in patients undergoing gastric
bypass.54 The analysis included 5 studies and a total of more than 10,000 procedures.
No significant difference was seen in post-operative bleeding rates between staplers
and sutures overall. Bleeding was more common with circular staplers (3.0%) than
with sutures (1.7%) and linear staplers (1.2%). Another analysis reported on rates of
anastomotic bleeding after loop ileostomy.55 The rate with staplers was low (1.0%),
but higher than for sutures.
al., Hand-sewn versus Stapled Closure of Loop Ileostomy: A Meta-Analysis, DIG SURG 2019;36(3):183-94; and
Markides, G. et al., Meta-Analysis of Handsewn versus Stapled Reversal of Loop Ileostomy, ANZ J SURG
2015;85(4):217-24. 44 Deng, X. et al. (2015), supra note 43. 45 Gong, J. et al. (2013), supra note 43. 46 Lovegrove, R. et al. (2006), supra note 43; Tieftrunk, E. et al., Pancreatic Stump Closure Techniques and
Pancreatic Fistula Formation after Distal Pancreatectomy: Meta-Analysis and Single-Center Experience,
PLOS ONE 2018;13(6):e0197553; Zhang, H. et al., Systematic Review and Meta-Analysis Comparing Three
Techniques for Pancreatic Remnant Closure Following Distal Pancreatectomy, BR J SURG 2015;102(1):4-15;
Zhou, W. et al., Stapler vs Suture Closure of Pancreatic Remnant after Distal Pancreatectomy: A Meta-
Analysis, AM J SURG 2010;200(4):529-36. 47 Tieftrunk, E. et al. (2018), supra note 46; Zhang, H. et al. (2015), supra note 46. 48 Jiang, H. et al. (2016), supra note 43; Gong, J. et al. (2013), supra note 43; Madani,R. et al. (2019), supra note
43; Markides, G. et al. (2015), supra note 43. 49 Gong, J. et al. (2013), supra note 43; Madani, R. et al. (2019), supra note 43; Markides, G. et al. (2015), supra
note 43. 50 Gong, J. et al. (2013), supra note at 43; Madani, R. et al. (2019), supra note 43; Markides, G. et al. (2015),
supra note 43; Lovegrove, R. et al. (2006), supra note 43. 51 Gong, J. et al. (2013), supra note 43; Madani, R. et al. (2019), supra note 43; Markides, G. et al. (2015), supra
note 43. 52 Jiang, H. et al. (2016), supra note 43; Madani, R. et al. (2019), supra note 43; Markides, G. et al. (2015), supra
note 43. 53 Lovegrove, R. et al. (2006), supra note 43; Liu, Q. et al. (2014), supra note 43. 54 Jiang, H. et al. (2016), supra note 43. 55 Madani, R. et al. (2019), supra note 43.
22 | P a g e
3.3.3. Summary of Articles Cited in FDA’s Proposed Order
As part of the “Data Upon Which the Reclassification Is Based” in its proposed
reclassification order, FDA cited 33 articles published over the last 26 years containing
information on safety outcomes with internal surgical staplers.56 These articles, which vary
significantly in design and quality, confirm the very low rates of complications and malfunctions
associated both with Medtronic stapling devices and internal staplers generally, and underscore
the fact that complications are more common in complex procedures and those performed by less
experienced surgeons.
3.3.3.1. Prospective Controlled Studies
FDA cites five prospective controlled studies, published between 2003 and 2007, providing
data on the safety of surgical stapling devices. Together these studies included more than 360
patients who underwent procedures in which Medtronic stapling devices (manufactured by its
predecessors Covidien, Tyco Healthcare, or United States Surgical) were used. Among those
patients, there were no deaths, fifteen reports of post-operative bleeding, one report of a post-
operative anastomotic leak, and three reports of “misfires.” Summaries of the studies are included
in Appendix 6.
3.3.3.2. Case Series / Case Reports / Retrospective Analyses
In addition to controlled studies, FDA’s proposed order cites 28 articles published over a
period of 26 years that report on procedures conducted with a variety of surgical stapling devices.
Sixteen of these articles, including 3,373 patients, reported on outcomes for procedures in which
Medtronic stapling products were used. In those reports, there were no device-related deaths, six
post-operative bleeds, thirteen post-operative anastomotic leaks, and 28 misfires or other device
malfunctions. Summaries of the studies are included in Appendix 7.
3.4. Conclusions
The totality of available evidence confirms the favorable benefit-risk profile of Medtronic’s
internal surgical stapling devices. Death and serious injuries associated with use of internal
surgical stapling devices are rare (reported rates less than 0.0005% and 0.017%, respectively), and,
in most cases, are related to inherent risks associated with the underlying surgical procedures or
with how the device is used during the procedure. Reported rates for complaints related to
Medtronic internal surgical stapling devices have been stable over the last seven years, and, in fact,
complaints involving serious injury have decreased significantly. Evidence from controlled
studies and meta-analyses provides additional reassurance regarding the safety profile of these
devices.
4. Enhancing Safe Use of Internal Surgical Stapling Devices
Medtronic’s internal surgical stapling products are safe devices that, over the past 50 years,
56 FDA, Proposed Order, General and Plastic Surgery Devices; Reclassification of Certain Surgical Staplers, 84
Fed. Reg. 17116, 17122-23 (Apr. 24, 2019).
23 | P a g e
have helped surgeons advance operative techniques. Safe use of internal surgical staplers requires
appropriate training and clinical judgment. As underscored by the studies cited in FDA’s proposed
reclassification order, this is particularly important where surgeons are attempting new and/or
more complex procedures.
Medtronic welcomes the opportunity to work with FDA and other stakeholders to further
enhance the safe use of internal surgical stapling devices. Medtronic supports reclassification and
developing a set of reasonable and appropriate standards for pre-clearance testing and labeling for
all internal surgical stapling devices. To that end, below, we provide a framework that we believe
will help ensure that all future internal surgical stapling devices cleared for use in the United States
are backed by appropriate testing and include appropriate information in the labeling to help
physicians make informed choices in the operating room.
4.1. Classification of Internal Surgical Stapling Devices
Medtronic supports FDA’s proposal to reclassify all internal surgical stapling products as
Class II devices subject to 510(k) clearance requirements. As discussed above, Medtronic has
treated its internal stapling devices (both “staplers” and “staples” in FDA’s parlance) as Class II
devices, has submitted the devices for clearance through the 510(k) pathway, and has conducted
pre-clearance testing to support its submissions. Medtronic welcomes FDA’s reclassification
proposal to ensure that all internal surgical stapling products comply with these same standards.
4.2. Proposed Special Controls
In its proposed order, FDA identified a series of “special controls” that the Agency believes
should be implemented for all internal surgical stapling devices prior to market clearance.57 As
reflected in the table below, FDA’s proposal appears to be consistent with the pre-clearance testing
Medtronic currently is conducting on our internal surgical stapling devices.
Table 4.1: FDA Proposed Special Controls vs. Current Medtronic Protocol
FDA Proposed Special Controls Type of Testing Current Medtronic Protocol
“Shelf-life testing must demonstrate that
the device maintains its performance
characteristics and the packaging of the
device maintains its integrity for the
duration of the proposed shelf-life.”58
Stability Testing
Stability testing conducted to support
the labeled shelf life of the devices.
“Additionally, because the risk of
infection can arise from a contaminated
device, sterility testing must demonstrate
the sterility of the device.”59
Sterilization Validation
Conducted in accordance with ISO
11135-1 and ISO 10993-7.
57 FDA, Proposed Order, General and Plastic Surgery Devices; Reclassification of Certain Surgical Staplers, 84
Fed. Reg. 17116, 17120-22 (Apr. 24, 2019). 58 84 Fed. Reg. 17116, at 17121. 59 Id.
24 | P a g e
FDA Proposed Special Controls Type of Testing Current Medtronic Protocol
“FDA believes that the device must be
demonstrated to be biocompatible because
the risk of adverse tissue reaction may
result from contact of the materials of the
device with the body.”60
Biocompatibility
Testing
Conducted in accordance with ISO
10993-1 and FDA Guidance, Use of
International Standard ISO 10993-1,
dated June 16, 2016.
“FDA believes that adequate performance
testing must include an evaluation of
staple formation characteristics in the
maximum and minimum tissue
thicknesses for each staple type;
measurement of the worst-case
deployment pressures on stapler firing
force; and a measurement of staple line
strength.”61
“Performance testing must also
demonstrate confirmation of staple line
integrity (e.g., through the absence of
vertically contiguous malformed staples),
as well as in vivo confirmation of staple
line hemostasis following staple
deployment.”62
“Examples of key performance
parameters include information on firing
the stapler, such as the firing force, pre-
fire compression time, and maximum
number of consecutive firings, and
information relevant to creating a staple
line, such as the percentage of properly
formed staples, number of incremental
firings required to complete a staple line,
and maximum number of reloads.”63
Performance Bench
Testing
In Vitro
Staple formation
Firing force
Reliability testing for
reusable staplers
In Vivo
External Atraumatic Tissue
Hemostasis
Pneumostasis
Staple formation
Knife cut
Anastomotic and transection
burst pressure
Radiographic / CT scans
Ex Vivo Animal Testing
Burst testing
Staple formation when fired
across intersecting staple
lines
“Usability testing and a labeling
comprehension study must demonstrate
that the clinician can correctly select and
use the device for its indicated use based
on the information in the labeling.”64
Human
Factors/Usability
Usability evaluation conducted
following IEC 60601-1-6 and IEC
62366-1 to demonstrate that the
subject devices meet product design
specifications by:
validating Instructions for Use
(IFU) and training
60 Id. 61 Id. 62 Id. 63 Id. 64 Id.
25 | P a g e
FDA Proposed Special Controls Type of Testing Current Medtronic Protocol
validating potential use error per
Risk and Hazard analysis
evaluating device performance
per design specifications
“If any components of the device are
reusable, the labeling must include
validated methods and instructions for
cleaning and sterilization of these
reusable components. Validation of
cleaning and sterilization instructions
must demonstrate that any reusable device
components can be safely and effectively
reprocessed per the recommended
cleaning and sterilization protocol in the
labeling.”65
Reprocessing Validation
Conducted in accordance with FDA
Guidance, Reprocessing Medical
Devices in Health Care Settings:
Validation Methods and Labeling,
dated March 17, 2015, and
subsequently updated on June 9, 2017.
Medtronic looks forward to working with FDA and other stakeholders to develop
standardized pre-clearance testing requirements that are reasonable, appropriate, and do not
impede patient access to these important medical devices.
4.3. Proposed Labeling
In its draft guidance, FDA recommended updating labeling for internal surgical stapling
devices, including proposed contraindications, warnings, directions for use, and technical
characteristics and performance parameters.66 While Medtronic believes that our current labeling
contains appropriate warnings and instructions for use, we would be pleased to work with FDA
and other manufacturers to develop a consistent framework for labeling across the class of internal
stapling devices, with a focus on helping surgeons make appropriate choices for their patients. We
plan to submit more detailed comments in response to FDA’s request for comment on its labeling
guidance and proposed reclassification order.
65 Id. 66 See FDA, Draft Guidance, Surgical Staplers and Staples for Internal Use - Labeling Recommendations (Apr.
24, 2019), https://www.fda.gov/media/123572/download.
26 | P a g e
APPENDIX
Appendix 1: 510(k) Clearance History
Type of Stapling
Product
510(k)
Number
Clearance Date
YYYY/MM/DD
Product Code
Referenced in
Company
510(k)
Submission
(Class)
Product Code
Referenced by
FDA in 510(k)
Clearance
(Class)
Product Names as
Submitted
Adapter and reload
for use with: EEATM
Stapler (Circular)
K182475 2019/03/14
(U.S. Launch
Forthcoming)
GDW (II)
GDW (II)
GAG (I)
SigniaTM Circular
Adapters (for use
with Signia
Staplers), Tri-
StapleTM 2.0
Circular Reloads
(for use with
SigniaTM Circular
Adapters)
Reload for use with:
Linear Cutting/
GIATM Stapler
(Articulating)
K173270 2018/02/20 GDW (II)
OXC (II)
GDW (II)
OXC (II)
Tri-StapleTM 2.0
Reinforced Reload
Circular/ EEATM
Stapler
K172361 2018/02/16 GDW (II) GDW (II)
GAG (I)
EEATM Circular
Stapler with Tri-
StapleTM
Technology
Cartridge for use
with:
Linear Cutting/ GIA
Stapler (Articulating)
K163098 2016/12/05 GDW (II)
GDW (II)
Tri-Staple™ 2.0
Intelligent
Cartridges
Linear Cutting/ GIA
Stapler (Articulating)
K160176 2016/04/26 GDW (II) GDW (II) SigniaTM Stapler
Loading Units w/
cartridges for use
with:
Linear Cutting/ GIA
Stapler (Articulating)
K151163 2015/05/29 GDW (II)
GDW (II)
Signia Loading
Units with Tri-
Staple™ 2.0
Cartridges
Reload for use with:
Linear Cutting/ GIA
Stapler (Articulating)
K133938 2014/01/22 ORQ (II) GDW (II)
ORQ (II)
Endo GIATM
Reinforced Reload
with Tri-StapleTM
Technology
Adapter for use with:
Linear Cutting/ GIA
Stapler (Articulating)
K133762 2014/01/08 GDW (II) GDW (II) Endo GIATM Extra
Long Adapter
Reload for use with:
Linear Cutting/ GIA
Stapler (Articulating)
K132493 2013/10/23 GDW (II)
GDW (II)
Endo GIA™
Radial Reload with
Tri‐Staple™
Technology
Type of Stapling
Product
510(k)
Number
Clearance Date
YYYY/MM/DD
Product Code
Referenced in
Company
510(k)
Submission
(Class)
Product Code
Referenced by
FDA in 510(k)
Clearance
(Class)
Product Names as
Submitted
Manual Adapter Tool
for use with Linear
Cutting/ GIA Stapler
(Articulating)
K123318 2012/12/18 GDW (II) GDW (II) Manual Adapter
Tool for iDrive™
Ultra Powered
Handle and Endo
GIA™ Adapter
Linear Cutting/ GIA
Stapler (Non-
Articulating)
K122781 2013/02/05 GDW (II) GDW (II) Reliamax™
Gastrointestinal
Anastomosis
Stapler and Reload
Linear Cutting/ GIA
Stapler (Articulating)
K121510 2012/07/25 GDW (II) GDW (II) iDrive™ Ultra
Powered Handle
and Endo GIA™
Adapter
Linear Cutting/ GIA
Stapler (Articulating
Linear Cutting/ GIA
Stapler (Non-
Articulating);
TIA or TA Stapler
(Non-Cutting)
K111825 2011/10/25 GDW (II)
GDW (II) Endo GIA™
Staplers,
DST Series™
GIA™ Staplers,
and
DST Series™
TA™ Staplers
Circular/ EEATM
Stapler
K093402 2009/11/12 GDW (II) GDW (II) Auto Suture™
EEATM OrvilTM
Circular/ EEATM
Stapler
K083781 2009/02/04 GDW (II) GDW (II) EEATM
Hemorrhoid
Stapler &
Accessories
Circular/ EEATM
Stapler
K062850 2006/10/23 GDW (II)
GDW (II)
GAG (I)
Auto Suture™
EEATM Surgical
Staplers
Circular/ EEATM
Stapler
K001895 2000/12/08 GDW (II) GDW (II) Auto Suture™
Premium Plus
CEEA™
Disposable Stapler
Staples for use with:
TIA or TATM Stapler
(Non-Cutting);
Linear Cutting/ GIA
Stapler (Non-
Articulating)
K921051 1992/07/16 Implantable
staple as Class II
pursuant to
§ 878.4750
Class II
(Product Code
Unspecified)
3M PreciseTM
Brand Internal
Surgical Staples
TIA or TATM Stapler
(Non-Cutting)
K912097 1991/09/19 Implantable
staple as Class II
pursuant to
§ 878.4750
Class II
(Product Code
Unspecified)
Auto Suture™
Endoscopic Fascia
Stapler
Staples for use with:
TIA or TATM Stapler
(Non-Cutting)
K911252 1991/07/25 Implantable
staple as Class II
pursuant to
Class II
(Product Code
Unspecified)
3M PreciseTM
Brand PI
Type of Stapling
Product
510(k)
Number
Clearance Date
YYYY/MM/DD
Product Code
Referenced in
Company
510(k)
Submission
(Class)
Product Code
Referenced by
FDA in 510(k)
Clearance
(Class)
Product Names as
Submitted
§ 878.4750 Disposable
Surgical Staples
TIA or TATM Stapler
(Non-Cutting)
K910192 1991/02/11 Class II
(Product Code
Unspecified)
Class II
(Product Code
Unspecified)
Auto Suture™
Endoscopic TA™
Surgical Stapler
TIA or TATM Stapler
(Non-Cutting)
K901107 1990/04/09 Unspecified Class II
(Product Code
Unspecified)
Modified Auto
Suture™
PURSTRINGTM
Disposable
Automatic Purse
String Instrument
Linear Cutting/
GIATM Stapler (Non-
Articulating)
K900129 1990/02/27 Unspecified Class II
(Product Code
Unspecified)
Modified Auto
Suture™
Endoscopic GIA™
Surgical Stapler
Staples for use with:
Linear Cutting/
GIATM Stapler (Non-
Articulating)
K885222 1989/02/03 Implantable
staple as Class II
pursuant to
§ 878.4750
Class II
(Product Code
Unspecified)
Precise ILA™ and
ILAN™ Surgical
Staples
Staples for use with:
Linear Cutting/
GIATM Stapler (Non-
Articulating);
TIA or TATM Stapler
(Non-Cutting)
K855047 1986/01/14 Class II
Unspecified Auto Suture™
Titanium Surgical
Staples
TIA or TATM Stapler
(Non-Cutting)
K843603 1984/10/31 Class II Unspecified Auto Suture™
Poly GIATM
Surgical Stapler
Cartridge used with:
TIA or TATM Stapler
(Non-Cutting)
K830199 1983/04/12 Class II, subject
to Performance
Standards
Unspecified Auto Suture™
TA™ Disposable
Staple Cartridge
with Absorbable
(Glycolide -
Lactide) Staples
TIA or TA™ Stapler
(Non-Cutting)
K801589 1980/08/04 Class II, subject
to Performance
Standards
Unspecified Auto Suture™
Disposable 30,
Disposable 55, and
Disposable 90
Surgical Staplers
Linear Cutting/
GIA™ Stapler (Non-
Articulating)
K801590 1980/08/04 Class II, subject
to Performance
Standards
Unspecified Auto Suture™
Disposable GIA™
Surgical Stapler
Type of Stapling
Product
510(k)
Number
Clearance Date
YYYY/MM/DD
Product Code
Referenced in
Company
510(k)
Submission
(Class)
Product Code
Referenced by
FDA in 510(k)
Clearance
(Class)
Product Names as
Submitted
TIA or TA™ Stapler
(Non-Cutting)
K780695 1978/06/22 Class I, subject
to
General Controls
&
Class II,
Performance
Standards
Unspecified Auto Suture™
Disposable
Stapling
Instruments
Circular/ EEA™
Stapler
K771178 1977/10/18 Class I, subject
to
General Controls
Unspecified Auto Suture™
EEA™ Stapling
Instrument
Appendix 2: Product Labeling
User Manual
Signia™
Stapling System
en
User Manual
Signia™
Stapling System
PT00032755
Table of Contents
1. System Overview. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1
2. Instructions for Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15
3. Cleaning and Sterilization. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .33
1
System Overview
1. System OverviewDescriptionSignia™ Stapling System The Signia™ stapler is an intelligent surgical stapler that provides push-button powered maneuverability and delivery of compatible stapling reloads. The Signia™ stapling system is the combination of the Signia™ stapler and system accessories.
The Signia™ stapler is composed of the Signia™ power handle, Signia™ power shell, and Signia™ adapters. The system accessories include a reusable insertion guide, a manual retraction tool, a single-bay charger, and a four-bay smart charger. The Signia™ stapler is compatible with Endo GIA™ single-use reloads and Endo GIA™ single-use reloads with Tri-Staple™ Technology .
Power Handle
The Signia™ power handle is a non-sterile reusable, battery-powered stapling handle that includes microprocessors, electronics, motors, a OLED display screen, and a rechargeable lithium-ion battery −all within a sealed handle.
Power Shell
The Signia™ power shell is a single-use, sterile shell that covers the non-sterile Signia™ power handle to create an aseptic barrier, control interface, and universal adapter connector.
Linear AdaptersThe Signia™ linear adapters are non-sterile reusable instruments that attach to the stapling handle to enable functionality of compatible stapling reloads. Included are motor mating connectors and electronic sensors. It is provided non-sterile and must be cleaned and sterilized prior to each use.
2
Signia™ Stapler Accessories Descriptions
Stapler Reusable Insertion GuideThe Signia™ reusable insertion guide is used to help maintain the sterility of the power shell during insertion of a non-sterile Signia™ power handle. It is provided non-sterile and must be cleaned and sterilized prior to each use.
Manual Retraction ToolThe Signia™ manual retraction tool is a reusable, handheld device that can be used to operate the adapter controls in the event of a malfunction during operation. The tool can be used to complete a firing, retract the knife and open the jaws, and/or articulate a stapling reload. It is provided non-sterile and must be cleaned and sterilized before use.
Single-Bay ChargerThe Signia™ single-bay charger is designed for use as an accessory to the Signia™ stapler and is used for charging the Li-ion batteries within the power handle. The charger will monitor the state of charge of a charging battery and report its status using color LEDs.
Four-Bay Smart ChargerThe Signia™ four-bay smart charger is designed for use as an accessory with the Signia™ stapler, which includes four power handle charging bays and a touch-screen LCD display screen. Its purpose is to charge the Li-ion batteries within the power handle. The touchscreen LCD is used to investigate the Signia™ power handle’s charge status.
CompatibilityThe Signia™ stapler is composed of the Signia™ power handle, Signia™ power shell and Signia™ adapters. Compatible accessories include a manual retraction tool, reusable insertion guide, a single-bay battery charger and four-bay smart charger. The Signia™
System Overview
3
System Overview
stapler is compatible with Endo GIA™ single-use reloads and Endo GIA™ single-use reloads with Tri-Staple™ Technology.
Indications for UseThe Signia™ stapler, when used with Endo GIA™ single-use reloads and Endo GIA™ single-use reloads with Tri-Staple™ Technology, has applications in abdominal, gynecological, pediatric, and thoracic surgery for resection, transection, and creation of anastomosis. It may be used for transection and resection of liver substance, hepatic vasculature, and biliary structures and for transection and resection of the pancreas.
The Signia™ stapler, when used with Endo GIA™ curved tip single use reloads can be used to blunt dissect or separate target tissue from other certain tissue.
The Signia™ stapler, when used with Endo GIA™ single use Radial Reloads with Tri-Staple™ Technology, has applications in open or minimally invasive general abdominal, gynecologic, pediatric and thoracic surgery for resection and transection of tissue and creation of anastomosis, as well as application deep in the pelvis, i.e., low anterior resection. It may be used for transection and resection of liver substance, hepatic vasculature and biliary structures and for transection and resection of the pancreas.
The Signia™ stapler, when used with Endo GIA™ single use reinforced reloads with Tri-Staple™ Technology preloaded with polyglycolic acid staple line reinforcement, has applications in abdominal, gynecologic, pediatric and thoracic surgery for resection, transection of tissue and creation of anastomosis. It may be used for transection and resection of liver substance, hepatic vasculature and biliary structures, and for transection and resection of the pancreas.
Contraindications1. Refer to the Instructions for Use provided with the compatible Endo GIA™ single-use reloads and Endo GIA™ single-use reloads with Tri-Staple™ Technology for specific indications, contraindications, warnings, and precautions.
2. Tissue thickness should be carefully evaluated before firing any stapler. Refer to the Instructions for Use provided with the selected Endo GIA™ single-use reload or Endo GIA™ single-use reload with Tri-Staple™ Technology for the specific contraindications regarding compressed tissue thickness for the selected reload.
3. Do not use the Signia™ stapler where adequacy of hemostasis cannot be verified visually after applications.
4. Do not use any linear cutter on major vessels without making provisions for proximal and distal control.
5. Do not use the instrument on ischemic or necrotic tissue.
4
6. The Signia™ stapler should not be used on friable or delicate tissue where the closure of the device might be destructive.
7. When using curved-tip reloads with the Signia™ stapler, do not use on tissue or structures that cannot fit completely within the reload jaws proximal to the transitional angle of the curved tip.
8. The Signia™ power shell is provided STERILE and is intended for use in a SINGLE procedure only. DISCARD AFTER USE. DO NOT RESTERILIZE.
9. Endo GIA™ single-use reloads and Endo GIA™ single-use reloads with Tri-Staple™ Technology are provided STERILE and are intended for use in a SINGLE procedure only. DISCARD AFTER USE. DO NOT RESTERILIZE.
Precautions and WarningsSystem-Specific Precautions and WarningsPrecautions1. This document is designed to assist in using this product. It is not a reference to surgical techniques.
2. Do not use the stapler if the packaging or device components appear damaged.
3. Endoscopic procedures should be performed only by physicians having adequate training and familiarity with endoscopic techniques. Prior to performing any endoscopic procedures, consult the medical literature relative to techniques, complications, and hazards.
4. The stapler and associated components are to be used by medical professionals qualified in the transportation, preparation, cleaning, sterilization, and use of surgical devices. Covidien™ single-use reloads are intended for use in a sterile operating room environment in surgical procedures where surgical stapling is indicated.
5. A thorough understanding of the principles and practices of electrical equipment is essential to avoid shock and other hazards to the operators and/or the device accessories. Ensure that electrical isolation and outlet grounding are not compromised.
6. The stapler is a precise instrument. Care should be taken to avoid dropping. Handling or cleaning the power handle improperly, or sterilizing it, may shorten device life and/or lead to device failure.
7. The power handle is provided non-sterile. DO NOT STERILIZE.
8. The adapters are provided non-sterile. Clean and sterilize before each use.
9. The reusable insertion guide is supplied non-sterile. Clean and sterilize before each use.
10. The manual retraction tool is provided non-sterile. Clean and sterilize before each use.
11. Do not hold or carry the stapler by the distal end of the adapter or by the stapling reload.
System Overview
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Warnings12. The power shell is provided STERILE and is intended for use in a SINGLE procedure only.
13. The stapler does not directly sense tissue thickness. Select the stapling reload with an indicated tissue range that is appropriate for the target tissue. Overly thick or thin tissue may result in unacceptable staple formation.
14. After firing staples and removing the instrument, always inspect the staple line and the surrounding site for hemostasis and/or leakage. Minor bleeding or leakage may be controlled by electrocautery or sutures.
15. When dividing major vascular structures, be sure to adhere to the basic surgical principles of proximal and distal control.
16. Failure to completely fire the stapling reload will result in an incomplete cut and/or incomplete staple formation, which may result in poor hemostasis and/or leakage.
Component-Specific Warning and PrecautionsRefer to component specific Instructions for Use for specific individual component warning and precautions.
Adverse ReactionsAdverse reactions, adverse events and potential complications may include but are not limited to:
• seroma/hematoma
• bleeding/hemorrhage/anastomotic leak
• fistula
• infection, which may include intraabdominal abscesses/sepsis
• ischemia
• chronic pain
• allergic reactions
• inflammatory reaction
• visceral adhesions
• nerve entrapment
• tissue erosion
• small bowel perforation
• potential for stricture
• potential for delayed gastric emptying, and the need for future re-operation.
System Overview
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System Indicators
A.
B.C.
D. E. F.
2
1
(1) LED INDICATORDuring use, the stapler uses an LED light, housed within the safety button, to indicate fully clamped status, readiness to fire, and fire-enabled status.
GREEN LED INDICATOR INDICATESOFF Stapling reload is not loaded or fully clamped
ON Stapling reload is fully clamped
BLINKINGThe green LED / safety button is pressed; device is entering firing mode
(2) OLED DISPLAY SCREEN INDICATORSGraphical display indicators provide additional device status and operative readiness for use in separate zones within the status border indicator frame.
OLED SYSTEM INDICATORS INDICATESA. System status
B. Power status
C. Reload recognition status
D. Power handle and power shell status
E. Adapter status
F. Reload status
System Overview
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BATTERY INDICATORS INDICATESGREEN
Functional, sufficient charge, available for use.
YELLOW
Functional, low battery indicator, available firings, available for use.
RED
Non-Functional, insufficient battery charge, not available for use.
Low battery status will indicate when there is enough battery charge to complete firing two linear staple reloads or cartridges. An insufficient battery charge will not allow you to continue to fire stapling reloads.
Component Status IndicatorsComponent status indicators will display the device life numerically for the stapler when setting it up.
When the setup completes, the stapler will indicate it is ready for use with an audible sequence of tones.
System Overview
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Table 10: Signia™ Stapler Set up Sequence1
Power handle procedures remaining
2
Insert power handle into power shell using
insertion guide indicator
3
Power handle, power shell status and attach an
adapter indicator
4
Power handle power shell, adapter status and attach a stapling reload indicator
5
Perform stapling reload cycle test before use
indicator
6
Ready for use stapler system status indicator
Operational Use IndicatorsThe stapler measures force when clamping and firing staples and will prevent the force from exceeding predetermined safety limits. As it enters three specially developed, predetermined force zones, the device will adjust and maintain its firing speed in each zone to optimize staple formation.
Table 11: Signia™ Stapler Firing Progress and Excessive Force Display - (e.g., using a 45mm reload)1
Pre-fire status
2
Fire travel to 30 mm indicator
System Overview
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3
Fire travel to 45 mm indicator
4
Excessive force indicator, firing stops
The handle LED light will illuminate green when fully clamped and flash when in fire mode.
Firing Process1. Press DOWN to fire and begin firing the stapler, the reload recognition bar fills green indicating firing progress.
2. Complete the fire when the knife reaches end of the reload and the reload recognition bar is completely filled green for the appropriate distance.
3. Press UP to retract the knife, the reload status bar and system status changes to inactive status indicating the device is no longer fully ready for use.
4. Upon completion of firing, the device with notify the user with an audible completion tone.
NOTE
The handle LED will flash green during fire mode and stay illuminated when firing is complete. The LED will turn off when the reload is opened.
In Table 12, Images (1-3) indicate using an Endo GIA™ single-use reload or Endo GIA™ single-use reloads with Tri-Staple™ Technology
System Overview
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Table 12: Signia™ Stapler Firing Progress Indicators - (e.g., using a 60 mm reload).
1 2 3
Reload travel distance indicators will display when using compatible Endo GIA™ single-use reloads and Endo GIA™ single-use reloads with Tri-Staple™ Technology.
Additional Controls IndicatorsThe Signia™ stapler’s power rotation controls are preset ON as ambidextrous, but can be configured for dedicated right- or left-handed use. Configuring rotation buttons can occur at any time once a Signia™ adapter is attached.
NOTE
The configuration will clear once the power pack is returned to the charger.
Disable/Re-Enable Rotation Button Controls1. Disable or re-enable rotation controls by pressing and holding both rotation buttons on one side of the handle for three seconds. The screen will show deactivation or reactivate countdown and change to its active status (see Table 13).
2. Pressing a single disabled rotation control will display the current disabled and active status.
System Overview
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Table 13: Signia™ Stapler Special Use Controls – Disabling and re-enabling the rotation button controls.
1 2Deactivation Sequence
Current Status
Re-activation Sequence
NOTE
Positive audible tones will notify when settings have been changed.
Manually Changing Firing SpeedsWhen fully clamped on tissue and in fire mode, the rotation buttons are turned off and are mapped into speed selection controls. Based on the force measured, the device will program the appropriate speed selection and faster speeds will not be available. To adjust to slower speeds, use the following steps:
1. Double click either lower rotation button to enter a slower speed setting. There are only three speed settings (Standard, Medium and Slow).
System Overview
12
NOTE
At any time the device measures higher force than programmed for a speed setting, the device will override the speed setting and move to a slower speed to optimize stapling performance.
Trouble Shooting IndicatorsIf faced with any of the following errors, document the error and replace the instrument.
Table 14: Signia™ Stapler Error Trouble Shooting Guide1
Battery error indicator
2
Power handle error indicator
3
General error indicator
4
Power shell error indicator
5
General adapter error indicator
6
General reload error indicator
NOTE
All fault conditions are notified with an audible fault tone
System Overview
13
End-of-Life IndicatorsIf faced with any of the following End-of-Life conditions, document the issue and replace the component.
Table 15: Signia™ Stapler End-of-Life Guide1
End-of-life service indicator – audible fault
tone notification
2
Used power shell attached indicator
3
End-of-life adapter indicator
4
Used stapling reload attached
System Overview
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15
2. Instructions for UseThese instructions are not intended as a reference to surgical techniques.
SET UPThree Hours Before First Use1. Each new power handle unit is shipped in the OFF mode. Turn it on by placing the base of power handle into a battery charging terminal from back to front until a secure connection is established. The device will turn on and begin initializing.
2. For its first activation, the power handle should charge for a minimum of three hours before clinical use.
Charging
NOTE
Refer to individual power charger Instructions for Use for additional information on set up and use.
PRECAUTION
Ensure that the power handle is sufficiently charged before use.
1. Insert the power handle into the battery charger, placing it into the battery charger bay facing forward and rock the base of the handle onto the terminal from back to front until a secure connection is established.
2. The charging cycle will start automatically when the power handle is inserted correctly into the battery charger.
Charging time will depend on the amount of charge remaining in the power handle. Full charging of an empty battery takes approximately three hours.
3. To remove the power handle from the battery charger, grasp the power handle and carefully rock from front to back while removing to release the secure connection.
Assembling The Signia™ StaplerBefore assembling the Signia™ stapler, refer to the power handle display set up support graphics for user-guided display feedback (Tables 10-15).
Instructions for Use
16
PRECAUTION
The power handle is non-sterile and CANNOT BE STERILIZED.
PRECAUTION
The power handle must be inserted into a sterile power shell with a sterilized reusable insertion guide while maintaining aseptic transfer principles. Use caution not to contaminate the sterile shell during power handle insertion.
PRECAUTION
Ensure that the power handle is sufficiently charged before use. Refer to the single-bay and four-bay smart charger sections in this manual or their individual Instructions for Use.
PRECAUTION
The reusable insertion guide is provided non-sterile. It must be cleaned and sterilized prior to each use.
Power Handle Insertion StepsStep 1 and 2
Reusable Insertion Guide
Step 3
Extended Remover handle
Step 4
Instructions for Use
17
Step 5
Secure Clips Display Screen Status
1. SCRUBBED PERSON: After aseptically removing the sterile power shell from the packaging, carefully open the shell by holding the back handle of the shell so the front handle is facing up and away from the back handle.
2. SCRUBBED PERSON: Align and fully seat a clean, sterilized reusable insertion guide onto the back handle of the open power shell to provide an aseptic transfer guide when inserting the power handle into the shell.
PRECAUTION
Ensure that the reusable insertion guide is properly seated onto the power shell and all clips are covered before inserting a power handle device.
3. CIRCULATING PERSON: While maintaining aseptic transfer techniques, insert the power handle into the insertion guide and power shell.
4. CIRCULATING PERSON: After the power handle is fully seated in the power shell, carefully remove the reusable insertion guide using the extended remover handle.
5. SCRUBBED PERSON: Taking care not to touch the power handle, close the front portion of the power shell until there is tactile confirmation the base of the shell is closed and the front clips are secured. Check all three clips to confirm the shell is fully closed and securely locked.
PRECAUTION
Ensure that both front clips are secured before use.
6. Confirm successful connection of the sterile control shell with the power handle and the functional status of the stapler on the display screen (see Table 10).
Instructions for Use
18
Attaching the Adapter
PRECAUTION
Signia™ adapters are REUSABLE and provided non-sterile. CLEAN and STERILIZE before use. Consult the Instructions for Use for the selected adapter for additional information.
PRECAUTION
Do not attach an adapter to the power shell prior to inserting a power handle.
PRECAUTION
Do not attempt to load a stapling reload before the adapter has been attached to the stapler and calibration has been completed. Doing so may lead to improper calibration and/or device damage.
NOTE
If a stapling reload is attached to the adapter before the adapter is attached to the stapler, the adapter will not calibrate for use.
PRECAUTION
If a stapling reload is attached to the adapter in a clamped or fired position before the adapter is attached to the stapling handle, the stapler will attempt to retract the knife blade and fully open the jaws. The stapler will not allow the stapling reload to fire until the reload is removed and the adapter completes its calibration.
Instructions for Use
19
1. Align the proximal end of the adapter with the quick release button facing up and in the same orientation as the stapling handle.
2. Simultaneously, press the two components together until the adapter is fully seated into the stapling handle and tactile feedback is registered.
3. Confirm secure attachment by pulling the adapter and power handle in opposite directions. The stapler will automatically begin to calibrate the adapter and the status indicator light on the display screen will illuminate as shown in Table 10.
Loading A Stapling Reload
WARNING
Always select a reload with the appropriate staple size for the tissue thickness. Overly thick or thin tissue may result in unacceptable staple formation.
PRECAUTION
Do not attempt to remove the shipping wedge until the reload is loaded onto the adapter.
IMPORTANT
When using compatible stapling reloads, refer to the indications, contraindications, warnings, and precautions described in the associated Instructions for Use.
When using the linear adapters and Endo GIA™ single-use reloads or Endo GIA™ single-use reloads with Tri-Staple™ Technology:
1. Insert the pin located at the distal end of the adapter into the stapling reload. Ensure that the LOAD alignment indicator on the reload aligns with the LOAD alignment indicator on the shaft.
2. Lock the reload in place by pushing it in and twisting clockwise 45 degrees (relative to the adapter). When loaded properly into the adapter, the reload unload button is seated in place without any red showing underneath.
Instructions for Use
20
3. Remove the shipping wedge from the reload.
4. Perform a reload cycle test to confirm proper loading of the stapling reload:
a. Press and hold the DOWN toggle button until the reload is fully clamped.
b. Press and hold the UP toggle button until the reload is fully open.
The power stapling handle will detect when the stapling reload is loaded, and the handle display will indicate a reload cycle test is required. Once the test is completed, the handle will indicate functional status and it is ready for use (see Table 10).
5. Verify that the functional ready status border on the display screen is solid green, as shown in Table 10.
6. At this point, the instrument is ready for use.
TroubleshootingDifficulty loading a stapling reload.
PRECAUTION
If there is difficulty loading a stapling reload, do not force it on.
If a stapling reload is difficult to load:
1. Recalibrate the adapter by removing the adapter from the stapler and reattaching it.
The adapter will recalibrate and indicate functional status and it is ready for use.
2. Reattempt to load a stapling reload.
NOTE
To prevent lengthy calibration steps between reload exchanges, center the reload position and fully open the jaws before removing reloads after each firing to prevent the need for calibration and to ensure safe and efficient reload exchanges. The device will also automatically center when removing the stapling reload. Holding the toggle in the up position for two seconds will completely open the reload and center articulation.
Instructions for Use
21
Difficulty Unloading A Stapling Reload
PRECAUTION
If there is difficulty unloading a stapling reload, do not force it off.
If a stapling reload is difficult to unload:
1. Center the reload and fully open the jaws by manually controlling the toggle or press and hold the UP control button for two seconds. The articulation will center and the jaws of the reload will fully open
2. Reattempt to unload the stapling reload by pressing the reload UNLOAD BUTTON back toward the power handle, twist the reload counterclockwise 45 degrees and remove the reload from the shaft of the adapter.
Operating the StaplerLinear Stapling Control InterfaceThe OPEN, CLOSE, and ARTICULATION controls are contained in a single toggle with a four-way activation control switch.
(1) RIGHT articulates the reload to the right when the cartridge is located in the up position.
(2) LEFT articulates the reload to the left when the cartridge is located in the up position.
(3) DOWN closes the jaws and will FIRE the staples when in fire mode.
(4) UP opens the jaws and will retract the knife when in fire mode.
1 2
3
4 A.
B.
A. Safety Button B. Rotation Control
Instructions for Use
22
The four–way activation TOGGLE provides two ways to activate the left and right articulation controls:
• (1) Use as a push button to control left – right movement or
• (2) Fit the index finger into the half-hemisphere, and push the center ridge or pull the side flare.
The SAFETY button can be pressed when the reload is fully closed to enable fire mode.
NOTE
When articulating the device back to center, the device will stop when the reload is at the center point.
The ROTATION controls are located on either side of the stapler and provide directional rotation control.
NOTE
When rotating the device, it will stop rotating at the 180 degree point from its last position.
Precision HandlingMaximize the precision of the powered stapler by:
• Grasping the handle using a comfortable, ergonomic position.
• Using the thumb, rather than the index finger, to actuate the green safety button to enable firing-mode.
• Using the index finger as the dedicated finger to actuate the four-way control toggle.
Instructions for Use
23
Operating Stapling Reloads
PRECAUTION
Do not attempt to insert or remove the instrument from the incision or trocar sleeve if the instrument is in the articulated position.
PRECAUTION
The anvil must be completely visible (past the trocar sleeve) prior to opening and/or articulating the reload within the body cavity.
WARNING
The instrument will cut and staple any structure included in the jaws. Use caution to ensure that only the intended structures to be cut and stapled are within the instrument jaws.
1. Once the appropriate sized stapling reload has been loaded, close the reload prior to introducing the instrument into the trocar sleeve or incision by pressing and holding the DOWN button.
2. Insert the instrument in the patient’s body cavity, press and hold the UP button to open the jaws of the instrument.
3. Position the jaws of the reload onto the target tissue by using the ARTICULATION and ROTATION buttons.
NOTE
The device can be manually rotated in addition to the push-button controlled rotation.
Instructions for Use
24
4. Clamp the tissue to be transected within the jaws of the reload. Use the UP and DOWN toggle buttons to use the instrument as a grasper to manipulate tissue.
WARNING
When positioning the stapler on the application site, ensure that no obstructions (such as clips) are within the instrument’s jaws. Firing over an obstruction may result in incomplete cutting action and/or improperly formed staples.
PRECAUTION
The instrument will not cut tissue beyond the black cut line indicated on the single-use reload. More than one application of the stapler may be necessary for tissue exceeding the length of the reload (30 mm, 45 mm, or 60 mm).
PRECAUTION
Placement of tissue proximal to the tissue stops on the reload may result in stapler malfunction. Any tissue extending beyond the cut line will not be transected.
5. Press and hold the DOWN button to close the jaws of the reload across the tissue to be transected. Confirm the reload is fully closed.
When the jaws of the reload are fully closed, an audible tone is indicated and the green LED light in the safety button is illuminated.
To optimize stapling performance, the Signia™ stapler uses the force measurements upon clamp and during firing to control the speed of fire.
NOTE
If the stapler must be repositioned when in fire mode, open the jaws by pressing the UP control button or press the green LED safety button again.
Instructions for Use
25
NOTE
The stapler will not fire staples or cut tissue until the green LED fire safety button is pressed.
6. Press and release the SAFETY button on either side of the stapler. An audible confirmation will occur and the LED indicator will flash green, indicating that the device is in fire-enabled mode.
7. Press and hold the DOWN/FIRE toggle button until the lower clamp cover reaches the distal end of the cartridge slot, and the powered handle stops. The firing-progress indicator will illuminate on the display to show the distance the reload has been fired (see Table 12).
8. To retract the knife blade after firing, press and release the UP control toggle.
NOTE
If required, firing can be stopped at any time by releasing the DOWN / FIRE button. To retract the knife before reaching the end of the reload, press and hold the UP / OPEN button.
9. To open the jaws after firing, press and hold the UP control toggle until fully opened.
WARNING
The stapler can be stopped and opened by pressing the UP toggle button. However, failure to completely fire the reload will result in an incomplete cut and/or incomplete staple formation, which may result in poor hemostasis and/or leakage.
10. Once the device has completed firing and the jaws open, the status indicator frame and the reload functional status indicator on the display screen will indicate completed firing status and is no longer able to be fired (see Tables 12-15). Remove the instrument from the tissue.
Instructions for Use
26
PRECAUTION
After firing and removing the instrument from the tissue, always inspect the staple line and the surrounding site for hemostasis and/or leakage.
11. After removing the instrument from the tissue, center the articulation by either:
• Using the four-way ARTICULATION toggle control. The articulation will pause when it has been centered.
• Pressing and holding the UP control toggle for two seconds.
12. Remove the instrument from the body cavity; the reload will spring closed during removal. Alternatively, press and hold the CLOSE/FIRE toggle button to close the jaws before removing the instrument from the body cavity.
PRECAUTION
Do not attempt to insert or remove the instrument from the incision or trocar sleeve if the instrument is in the articulated position.
13. If additional firings are desired on the same patient, attach a new single-use reload.
PRECAUTION
When using the stapler more than once during a single surgical procedure, be sure to remove the empty stapling reload or cartridge and load a new one. A safety interlock prevents an empty single-use reload from being fired a second time. Do not attempt to override the safety interlock.
Center the reload and fully open the jaws before removing the reload to ensure efficient reload exchanges.
TroubleshootingFiring Slows DownThe Signia™ stapler measures force when clamping and firing staples and will prevent the force from exceeding predetermined safety limits. As it enters three specially
Instructions for Use
27
developed, predetermined force zones, the device will adjust its firing speed in each zone to optimize staple formation.
If the stapler slows down during firing before the lower clamp cover reaches the distal end, it is likely the firing force reached the force zone threshold and moved into the next force zone level and the device firing speed was slowed to optimize stapling performance.
Incomplete FiringIf the stapler stops firing before the lower clamp cover reaches the distal end, it is likely the firing force measured reached the upper design limit of the stapling reload. Carefully assess the tissue to determine whether to attempt to complete the firing.
PRECAUTION
When dividing major vascular structures, adhere to the basic surgical principles of proximal and distal control.
If the stapler stops while firing:
1. Release the DOWN/FIRE button, and any other button or toggle that may be pressed.
2. Inspect the stapling reload for an obstruction, excessively thick tissue, or for completion of firing.
3. If continued firing is desired, attempt to complete the firing by pressing and holding the DOWN/FIRE button until completion of firing.
4. If the stapler is unable to complete the firing, press UP on the toggle to RETRACT the knife of the reload to the fully clamped position. Press and hold UP/OPEN again to fully open the jaws of the stapling reload.
5. If unsuccessful in removing the stapling reload from the tissue, refer to the Instructions for Use section to remove the reload. If that fails, follow the instructions described in the Alternate Opening Procedure or in the Manual Retraction Tool Procedure.
Alternative Opening ProceduresIf the stapler failed to remove the stapling reload from the tissue, the following procedures may be used to attempt to retract the knife and open the jaws of the reload.
The alternative opening procedures can be performed using the existing power stapler or with a new power stapler if a replacement power handle and sterile control
Instructions for Use
28
shell is available. Insert a charged power handle into a sterile control shell, following the instructions in the Assembling The Signia™ Stapler section.
WARNING
Depending upon the potential failure mode, each of the processes described below may or may not be successful in retracting the knife and opening the stapling reload. Professional experience should be used to assess patient status when deciding the best course of action.
PRECAUTION
When dividing major vascular structures, adhere to the basic surgical principles of proximal and distal control.
I. Powered Opening Approach
PRECAUTION
Care should be taken to support the adapter during disassembly to prevent tissue damage.
1. Remove the stapling handle from the adapter by pressing the QUICK RELEASE button on the top of the adapter while simultaneously pulling the stapling handle off of the adapter.
2. Reattach the stapling handle onto the adapter and connected reload. Upon connection to the adapter, the device will run through a calibration process and recognize if a reload is attached. It will then attempt to zero out the controls forcing the knife to retract and open the stapling reload.
3. Once the stapling reload is disengaged from tissue, remove the power stapling handle from the patient and inspect the staple line and surrounding tissue for hemostasis and/or leakage.
If the powered opening approach is unsuccessful, attempt a reboot and follow the reattachment steps (2-3) as indicated above.
Instructions for Use
29
II. Rebooting the power handle
Another way to open the stapling reload is to reboot the power handle.
During a reboot, the device will run through a calibration process and recognize if a reload is attached. It will then attempt to zero out the controls, forcing the knife to retract and open the stapling reload. A reboot can be performed while attached to the adapter and stapling reload or separately.
PRECAUTION
Rebooting the power handle during a firing or incomplete firing will stop the firing process, retract the knife blade, and open the jaws of the stapling reload.
1. To force a reboot, simultaneously press and hold both SAFETY buttons for ten seconds.
2. Release the SAFETY buttons. The device will reboot.
3. Once the stapling reload is disengaged from tissue, remove the stapler from the patient and inspect the staple line and surrounding tissue hemostasis and/or leakage.
III. Using the Manual Retraction Tool
If another power stapler is not available, or the powered opening procedure and the reboot approaches are unsuccessful, use the manual retraction tool procedure.
WARNING
The manual retraction tool is intended to be used as a back-up device for the stapler should the stapler experience a failure during operation. It can be used to complete a firing that has already been initiated, or to retract the knife and open the jaws to remove a reload from tissue. It should NOT be used to initiate a new firing of a stapling reload.
PRECAUTION
The manual retraction tool can only be used as a backup for the stapling handle. Should a failure occur in either the stapling reload or adapter, the stapling reload may not respond to inputs from the manual retraction tool.
Instructions for Use
30
WARNING
The manual retraction tool is provided non-sterile. Clean and sterilize before each use.
1. Remove the power stapling handle from the adapter by pressing the black QUICK RELEASE button on the adapter while pulling the handle off the adapter.
PRECAUTION
Care should be taken to support the adapter during disassembly to prevent tissue damage.
2. To control the firing, insert the manual retraction tool into the center hole marked with a one (1) on the proximal end of the adapter.
3. To continue firing the stapling reload, turn the manual retraction tool counterclockwise, opposite direction of the arrow.
4. To retract the knife and open the jaws of the stapling reload, turn the manual retraction tool clockwise, the same direction as the arrow.
PRECAUTION
Retracting the knife and opening a fully fired stapling reload using the manual retraction tool may take up to ten minutes. The user should consider this when deciding on the best course of action in the event of a failure of the power stapling handle.
5. If the reload is articulated, insert the manual retraction tool into the hole marked with a two (2) on the proximal end of the adapter. If the stapling reload is orientated so that the lower clamp cover is up and the anvil is down, turning the manual retraction tool counterclockwise will articulate the reload to the right. Turning it clockwise will articulate the reload to the left.
6. Once the reload is centered, remove the instrument from the patient. Refer to the instructions in the Disassembling the Stapler section.
Instructions for Use
31
WARNING
When a manual retraction tool is used in a procedure, do not attempt to reuse the power stapler, power handle, adapter, or the stapling reload. Contact Covidien customer service for return instructions.
PRECAUTION
After firing and removing the instrument from the patient, always inspect the staple line and the surrounding site for hemostasis and/or leakage. Minor bleeding or leakage may be controlled by using electrocautery or sutures.
WARNING
When a device malfunction occurs in a procedure, do not attempt to reuse the stapler, adapter, or the stapling reload. Contact Covidien customer service to determine diagnostic service and return options.
Disassembling the StaplerUnloading A Stapling Reload 1. Once articulation is centered and the jaws are open, pull the blue UNLOAD button back to release the stapling reload, twist the reload counterclockwise 45 degrees, and pull the reload from the shaft of the adapter to remove it.
2. Dispose of the single-use reload per local procedures and regulations for biohazard waste materials. Do not attempt to reuse or resterilize single-use reloads.
TroubleshootingDifficulty Removing Stapling Reload And CartridgeIf a stapling reload is difficult to remove:
1. Simultaneously press and hold the UP control button for two seconds. The articulation will center, and the jaws of the reload will fully open.
2. Press the reload UNLOAD BUTTON back toward the power handle, twist the reload counterclockwise 45 degrees and remove the reload from the shaft of the adapter.
Instructions for Use
32
Removing The Adapter To remove the adapter:
1. Press and hold the adapter QUICK RELEASE button while pulling the adapter off of the power stapling handle.
2. Refer to the specific adapter Instructions for Use for Cleaning and Sterilizing instructions.
Removing The Power Shell And Power Handle
WARNING
The power handle cannot be sterilized.
PRECAUTION
The power handle will continue to drain power from the battery as long as it remains attached to the power shell. Upon completion of use and disinfection, return the used power handle to the battery charger station.
WARNING
The power shell is single-use only. DISCARD AFTER USE. DO NOT STERILIZE. Re-sterilized or reprocessed sterile power shells will not function.
1. Open the power shell by first releasing the side secure clips.
2. While holding the back of the power shell, press the bottom release button down and push under the latch to open the power shell.
3. With clean gloves, securely remove the power handle from the power shell and place it in a clean environment.
4. Discard the used power shell.
5. Follow the disinfection instructions for the power handle in the Cleaning section.
Instructions for Use
33
3. Cleaning and SterilizationCleaningAfter UseReprocess the instruments as soon as possible following use. If reprocessing cannot be performed immediately, cover the instruments with a moist towel.
Only use the cleaning methods described for the reusable components as indicated in the individual Instructions for Use. Discard the single-use power shell after use.
SterilizingThe adapters, manual retraction tool, and the reusable insertion guide are provided non-sterile. They may be sterilized by steam autoclave or EtO methods. Only use the sterilization methods described in the individual Instructions for Use.
WARNING
The power handle is non-sterile and cannot be sterilized. Do not immerse. The power handle will be damaged if sterilization is attempted.
Recycling And Disposal
NOTE
Contact customer service prior to recycling and disposing of power handle to confirm contracted recycling and disposal agreements. Contact Covidien customer service at http://www.covidien.com/sales-support, or by phone: 1-800-722-8772. Recycle the power handle by returning it to the manufacturer.
Discard or recycle the adapter, reusable insertion guide, manual retraction tool, and other accessories as per local, state, and governmental regulations.
Cleaning and Sterilization
© 2016 Covidien. Covidien llc, 15 Hampshire Street, Mansfield, MA 02048 USA.
Covidien Ireland Limited, IDA Business & Technology Park, Tullamore, Ireland.www.Covidien.com+1 800 633 8766+1 763 514 4000Covidien, Covidien with logo, and Covidien logo and Positive Results for Life are U.S. and internationally registered trademarks of Covidien AG. Other brands are trademarks of a Covidien company, ™* brands are trademarks of their respective owner. 2016 / 04 - 3
0123
Do not use ifpackage is opened
or damaged
Consult instructions
for use
Caution, consultaccompanying
documents
Transport atmospheric pressure limitations
54.9 kPa
101.3 kPa
Transport humidity limitation
90%
-20.2 °F-29 °C
140 °F60 °C
Transport temperaturelimitations
Type CFApplied Part
Protection against fluid ingress: Drip-proof
Appendix 3: Training Program Agenda
Appendix 4: ASR Communication
Appendix 5: Medtronic Sponsored Studies
Jacobs, E. et al., Does Manufacturer Influence Staple Line Complications in Bariatric
Procedures? A Meta-Analysis of Post-Operative Complication Rates (2019). This was a meta-
analysis of 65 peer-reviewed articles, including 24,040 patients, evaluating rates of post-operative
complications in patients undergoing bariatric procedures in North America, Europe, Asia, Africa,
and South America. The analysis showed that Medtronic stapling products have low rates of post-
operative leaks (0.88%), post-operative bleeding (1.55%), and post-operative strictures (3.29%),
when used in bariatric procedures. (Data on file at Medtronic).
Jacobs, E. et al., What Influences Staple Line Complications in Colorectal Procedures? A
Meta-Analysis of Post-Operative Complication Rates (2019). This was a meta-analysis focusing
on colorectal procedures, which included data from 62 peer-reviewed articles including 14,743
patients. Despite including complex rectal and malignancy related procedures, overall rates of
post-operative leaks (5.42%), post-operative bleeding (2.07%), and post-operative strictures
(2.16%) were low with, Medtronic stapling devices. (Data on file at Medtronic).
A Post Market Study of the Endo GIA™ Reinforced Reload with Tri-Staple™ Technology
(2017), NCT02500537. This was a prospective, multi-center, two-arm (thoracic and abdominal)
post market study which tracked the outcomes of the Endo GIA™ Reinforced Reload with Tri-
Staple™ Technology. Of the 100 patients enrolled, a total of three device-related adverse events
were reported (3%). There were no instances of intra-operative staple line bleeding. One instance
of gastrointestinal leak (1.7%), three air leaks in the thoracic arm (7.5%), and five reports of post-
operative infection at the operative site (5%) were reported and deemed to be procedure-related.
Two deaths were reported during the study; neither was deemed device-related (one aortic rupture,
one cerebral hemorrhage).
Man-I, M. et al., Totally Intracorporeal Delta-Shaped B-I Anastomosis Following
Laparoscopic Distal Gastrectomy Using the Tri-Staple™ Reloads on the Manual Ultra Handle:
a Prospective Cohort Study with Historical Controls, SURG ENDOSC 2015;29:3304-12. This was
a prospective study of 23 consecutive patients who underwent a curative totally laparoscopic
Billroth I gastrectomy with delta-shaped anastomosis using the Endo GIA™ Reloads with Tri-
Staple™ technology. These patients were matched with 19 patients previously treated using the
ENDOPATH® ETS Articulating Linear Cutter, and short-term surgical outcomes were compared.
There were no differences between the two populations in morbidity, anastomosis-related or non-
anastomosis-related complications, total systemic complications, or short-term outcomes, with the
exception of intraoperative bleeding from the staple line which was significantly less in the Tri-
Staple™ population. There were no patient deaths in the series.
Ito, H. et al., The Efficiency and Safety of Variable-Height Staple Technology in Pulmonary
Resections, CLIN SURG. 2018;3:2091. This was a prospective study of 60 patients undergoing
resection of the pulmonary parenchyma with Tri-Staple™ Technology reloads. The authors
reported a low incidence of prolonged pulmonary fistula (1.7%) and intraoperative air leaks (8.1%,
14/172 firings). No air leaks were observed at the stumps or overlapping sites. The only adverse
event reported was a reoperation for the prolonged pulmonary fistula.
Okami, J. et al., Randomized Study Comparing Equal Height Staples with Graduated Height
Staples in Bronchial Closure, ANN THORAC SURG 2017;104:1012-19. This was a randomized
prospective study of 61 patients (183 staple lines) undergoing lobectomy, evaluating staple
formation on the resected bronchial stump. The percentage of staples that formed a complete “B”
shape was significantly higher in the graduated height staples than in the equal height staples. No
difference was observed by the authors in regards to postoperative complications. No
bronchopleural fistula was observed.
Kawai, M. et al., Reinforced Staplers for Distal Pancreatectomy, LANGENBECKS ARCH SURG
2017;402:1197-1204. This was a prospective multicenter single arm study with 121 enrolled
patients undergoing distal pancreatectomy using Endo GIA™ with Reinforced Reloads. Clinically
relevant pancreatic fistula occurred in 13/105 patients (12.4%). Mortality rate was 0%.
Reoperations were performed on two patients (1.9%).
Misawa, K. et al., Safety and Feasibility of Linear Stapling Device with Bioabsorbable
Polyglycolic Acid Sheet for Duodenal Closure in Gastric Cancer Surgery: A Multi-Institutional
Phase II Study, WORLD J SURG. 2019;43:192-98. This was a prospective multicenter study of
100 patients with gastric cancer undergoing distal or total gastrectomy with R-Y reconstruction.
In all cases the duodenum was transected with a Endo GIA™ with Reinforced Reload.
Postoperative duodenal stump fistula was observed in two cases (2.0%). Intraoperative bleeding
at the duodenal staple line was observed in one case and easily controlled without additional
suturing. There were no instances of postoperative bleeding, duodenal serosal injury or patient
death. Of the 43 patients who underwent the procedure laparoscopically, one required conversion
to open approach.
Appendix 6: Prospective Studies Cited by FDA
Champion, J. et al., Prospective Randomized Comparison of Linear Staplers During
Laparoscopic Roux-en-Y Gastric Bypass, OBES SURG 2003;13(6):855-60. This prospective
study compared United States Surgical’s Endo GIA™ Universal 6-row stapler with Ethicon’s
ETS-Flex 6-row stapler during 100 laparoscopic Roux-en-Y gastric bypass procedures. “The ETS-
Flex group experienced significantly more stapler misfires, hemoclips applied for staple-line
bleeding, estimated blood loss, and OR time, compared to the Endo-GIA group.” In the Endo
GIA™ group, there was one misfire (described as “minor” and involving “a 45-mm stapler with
3.5 mm stapler cartridge which would not load on handle”), no leaks, and two post-operative
bleeds. None of the patients had any long-term complications.
Angrisani, L. et al., The Use of Bovine Pericardial Strips on Linear Stapler to Reduce
Extraluminal Bleeding During Laparoscopic Gastric Bypass: Prospective Randomized Clinical
Trial, OBES SURG 2004;14(9):1198-1202. This prospective study evaluated whether use of
bovine pericardial strips on Endo GIA™ linear staplers manufactured by United States Surgical
would reduce bleeding during laparoscopic gastric bypass. Among 98 patients, the authors noted
one “linear stapler misfire.” They reported no leaks, post-operative bleeding, or reoperations. The
authors noted that the limited number of cases did not allow them to evaluate the stapler device.
Nguyen, N. et al., Glycolide Copolymer Staple-Line Reinforcement Reduces Staple Site
Bleeding During Laparoscopic Gastric Bypass, ARCH SURG 2005;140(8):773-78. This
prospective randomized trial involved 34 patients who underwent laparoscopic gastric bypass,
evaluating whether reinforcement of a linear stapler manufactured by United States Surgical (the
specific device was not identified) with a glycolic copolymer sleeve reduced rates gastrointestinal
hemorrhage. The authors reported one stapler misfire in 281 stapler loads (0.3%), occurring in the
treatment group receiving a reinforcement sleeve. There was no mortality, no post-operative leaks,
and one event of gastrointestinal bleeding. No patient was converted to open procedures.
Kaushik, M. et al., Comparison of Techniques of Vascular Control in Laparoscopic Donor
Nephrectomy: The Leicester Experience, TRANSPLANT PROC 2006;38(10):3406-08. This
prospective study compared the safety and efficacy of laparoscopic donor nephrectomy procedures
using Ethicon Endo-Surgery ETS staplers, a polymer clip, or “endoclips” in 106 patients. The
authors reported “one episode of stapler malfunction in renal vein division that required the use
of a second device.”
Simper, S. et al., Comparison of Laparoscopic Linear Staplers in Clinical Practice, SURG OBES
RELAT DIS 2007;3(4):446-51. This prospective study involved 400 patients who underwent
laparoscopic gastric bypass using either Tyco’s Endo GIA™ Universal 6-row stapler or Ethicon’s
ETS-45 6-row stapler. In the Tyco group, there were no misfires, one staple line leak, six events
of gastrointestinal bleeding, two events of staple line bleeding, and five events of “unexplained
intra-abdominal bleeding.” None of the bleeding complications were attributed to a device
malfunction. The authors concluded that “both devices were equally safe and effective.”
Appendix 7: Case Reports, Series, and Retrospective Studies Cited by FDA
Kyzer, S. et al., Experience with the Use of the Circular Stapler in Rectal Surgery, DIS COLON
RECTUM, 1992;35(7):696-706. This article evaluated the experiences of 214 patients who
underwent end-to-end anastomoses using EEA™ and CEEA™ circular staplers manufactured by
United States Surgical. The authors noted five events of “instrument failure,” including one staple
misfiring and four incomplete cuts resolved by transecting remaining tissue with a scalpel in three
cases and creating a new anastomoses with an EEA stapler in the fourth. The authors reported a
single early postoperative leak, corrected with a transverse colostomy on the tenth postoperative
day, and no instances of postoperative bleeding. They further noted one postoperative death in the
patient population unrelated to the anastomosis. The authors concluded that their “[e]xperience
gained with the circular stapling device has shown it to be a reliable method of performing
anastomoses to the rectum in a safe and expeditious manner.”
Allen, M. et al., Video-Assisted Thoracoscopic Stapled Wedge Excision for Indeterminate
Pulmonary Nodules, J THORAC CARDIOVASC SURG 1993;106(6):1048-52. This article evaluated
a series of patients who underwent video-assisted thoracoscopy for indeterminate pulmonary
nodules. 85 patients underwent a wedge excision, using an Endo GIA™ stapler manufactured by
United States Surgical. The authors reported one stapler “malfunction” which required conversion
to an open procedure. They reported no deaths and no post-operative bleeds. The authors
concluded that “thoracoscopic wedge excision is a safe and effective procedure in selected patients
with an indeterminate pulmonary nodule.”
Kim, C. et al., Roux-en-Y End-to-Side Esophagojejunostomy with Stapler After Total
Gastrectomy, YONSEI MED J 1993;34(4):334-39. This article examined a series of 100 gastric
cancer patients who underwent total gastrectomy with Roux-en-Y esophagojejunostomy in South
Korea using United States Surgical’s EEA™ and TA™ stapling devices. Across all the
procedures, there were two “misfires” (the stapler could not be fired, and the problem was resolved
by restapling), two asymptomatic post-operative leaks, and two cases of post-operative stricture.
The authors reported no deaths, bleeds, or other post-operative complications. They concluded:
“we performed 100 consecutive esophagojejunostomies with stapling devices without
any serious complication and could save total operating time. We think that the stapler,
when properly used, can facilitate the esophagojejunostomy safe ly and routine use of
the Levin tube after total gastrectomy may be unnecessary.”
Yim, A. et al., Malfunctioning of Vascular Staple Cutter During Thoracoscopic Lobectomy, J
THORAC CARDIOVASC SURG 1995;109(6):1252. The authors reported a single event where a
Multifire Endo GIA™ stapler manufactured by United States Surgical “transected the vein but
failed to fire” during a video-assisted thoracoscopic surgical procedure. The patient recovered
uneventfully. The authors noted that they inserted the instrument into the chest cavity without
using an instrument port and acknowledged that “pressure from the rib during insertion on [sic]
the shaft could be the reason for the malfunctioning of the stapler.”
Pandya, S. et al., Laparoscopic Colectomy: Indications for Conversion to Laparotomy, ARCH
SURG 1999;134(5):471-75. This article reported the rates of conversion to open procedures in 200
patients who underwent laparoscopic colectomy. The authors reported an overall conversion rate
of 23.5% (47 of the 200 patients), two of which they attributed to “stapler misfire.” The type of
stapler was not identified. The authors further noted that they maintain a patient registry and have
not identified any port-site or incisional metastases in their series. The authors concluded that
“[e]volving technology has made it possible to accomplish goals that were previously
unattainable” and suggested that “it is likely that a laparoscopic approach may become the
preferred method for treating a variety of colorectal disorders.”
Chan, D. et al., Endovascular Gastrointestinal Stapler Device Malfunction During
Laparoscopic Nephrectomy: Early Recognition and Management, J UROL 2000;164(2):319-21.
The authors evaluated the incidence of endovascular stapler “malfunctions” during nephrectomy
procedures. In a series of 565 laparoscopic procedures performed with gastrointestinal
anastomosis (“GIA”) staplers manufactured by United States Surgical and Ethicon, the authors
identified ten “malfunctions,” three attributed to instrument failure and seven to “preventable
causes.” The authors reported no patient deaths and no post-operative bleeding complications.
They concluded that “[u]se of the GIA stapler is standard for control of renal hilar vessels during
laparoscopic nephrectomy. Failure of the device is uncommon and is usually related to preventable
causes.”
Asamura, H. et al., Mechanical Vascular Division in Lung Resection, EUR J CARDIOTHORAC
SURG 2002;21(5):879-82. The authors evaluated the relative advantages of stapling over ligation
for major pulmonary vessels in lung resection. In a series of 842 mechanical vascular divisions
performed with either Ethicon’s Endopath Endocutter staplers or United States Surgical’s Endo
GIA™ staplers, the authors reported “only one incidence of stapling failure” (overall stapling
failure rate of 0.1%), caused by “misalignment of the cartridge during insertion of the stapler.” No
bleeding events requiring reoperation occurred. The authors concluded that, despite the fragility
of pulmonary vascular walls, “vascular division with endostaplers was highly reliable with only a
0.1% incidence of stapling failure for all kinds of vascular structures in the thorax.”
Deng, D. et al., Laparoscopic Linear Cutting Stapler Failure, UROLOGY 2002;60(3):415-19.
The authors reported five cases of gastrointestinal anastomosis stapler malfunction, among 460
laparoscopic urologic procedures. The authors used a laparoscopic endovascular stapler
manufactured by Ethicon. Three of the events resulted in conversion to an open procedure. The
authors did not report any post-operative complications and no deaths. An editorial comment
following the article noted that “most failures are preventable and occur as a direct consequence
of surgeon or surgical team error. Indeed, cases of primary device failure (eg, manufacturer’s
defect) are actually very rare (about 0.3%).”
Dresel, A. et al., Establishing a Laparoscopic Gastric Bypass Program, AM J SURG
2002;184(6):617-20. This article examined a series of 100 patients who underwent Roux-en-Y
gastric bypass procedures conducted in a newly developed bariatric surgery program at a
community hospital. All procedures used Ethicon’s 45-mm ETS endoscopic linear stapler and 21-
mm Endopath ILS™ endoscopic circular stapler. The authors reported numerous complications
and three equipment malfunctions in the first 60 patients, but noted no complications in the last
40. The authors concluded that “Roux-en-Y gastric bypass is a technically challenging procedure
that can be safely integrated into a bariatric treatment program with good results. Improved
outcomes, shorter operative times, and fewer complications are associated with increased surgical
experience.”
Ky, A. et al., One-Stage Laparoscopic Restorative Proctocolectomy: An Alternative to the
Conventional Approach? DIS COLON RECTUM 2002;45(2):207-11. This article evaluated a
series of 32 patients with mucosal ulcerative colitis and familial adenomatous polyposis who
underwent one-stage laparoscopic-assisted restorative proctocolectomy. The authors reported one
staple line misfire associated with a Covidien PI™ 30 stapling device, “which was remedied by
oversewing the anorectal stump with interrupted sutures, followed by the creation of a circular-
stapled anastomosis.” The misfire did not require conversion to open surgery, and there were no
post-operative bleeds. There was one pouch leak reported. The authors concluded that “[a] one-
stage laparoscopic-assisted restorative proctocolectomy can be performed effectively and safely.”
Mattioli, G. et al., Complications of Mechanical Suturing in Pediatric Patients, J PEDIATR
SURG 2003;38(7):1051-54. The authors evaluated a series of 174 thoracic and gastrointestinal
procedures performed in pediatric patients using circular PCEEA™ and linear GIA™ and Endo
GIA™ staplers manufactured by United States Surgical. Across the procedures, there were two
“technical problems” with staplers, seven bleeding events, and two leaks. Of the bleeding events,
only one was post-operative. No deaths occurred. The authors noted that “[a]ll major
complications were caused by erroneous choice of conventional not endoscopic stapler” and
concluded that stapling “could improve patient outcome with a limited risk of complications” in
some pediatric surgical procedures.
Folkesson, J. et al., The Circular Stapling Device as a Risk Factor for Anastomotic Leakage,
COLORECTAL DIS 2004;6(4):275-79. The authors conducted a questionnaire and database review
from Sweden evaluating anastomotic leakage rates in patients who had an anterior resection for
rectal cancer with two unidentified circular stapling devices. The article reported leakage rates of
11% and 7% for the two devices, and the authors noted that “[a] gross leakage of 9% in [anterior
resection] is acceptable . . . when compared to results in other studies.”
Szwerc, M. et al., Minithoracotomy Combined with Mechanically Stapled Bronchial and
Vascular Ligation for Anatomical Lung Resection, ANN THORAC SURG 2004;77(6):1904-10. This article examined 713 patients who underwent anatomic pulmonary resection using United
States Surgical’s Endo GIA™ port-access endostapler. The authors experienced one staple
misfiring, requiring conversion to open and resulting in intraoperative bleeding, but the patient
made a full recovery. The overall adverse event rate during stapler application was 0.27%. The
authors reported no device-related deaths, one post-operative bleeding event, and nine prolonged
air leaks. They concluded that “[t]he combination of the minithoracotomy performed through a
vertical axillary incision with total mechanical stapled bronchovascular ligation seems to be safe
and expeditious. A low number of complications were observed with this technique.”
Nadu, A. et al., Laparoscopic Nephrectomy: Initial Experience in Israel with 110 Cases, ISR
MED ASSOC J 2005;7(7):431-34. This article summarized the first 110 laparoscopic nephrectomy
cases conducted at an institution in Israel. The authors reported one “malfunction” of a Covidien
Endo GIA™ stapler leading to severe bleeding, as well as five vascular injuries unrelated to stapler
use. No perioperative mortality was noted. The authors concluded that “laparoscopic
nephrectomy can be considered a routine, safe and effective procedure associated with minimal
morbidity and significant advantages for the patient.”
Rosenblatt, G. et al., Clipless Management of the Renal Vein During Hand-Assist Laparoscopic
Donor Nephrectomy, BMC UROL 2006;6:23. The authors evaluated 50 clipless laparoscopic
donor nephrectomies performed with either United States Surgical’s LigaSure™ vessel sealing
device or its Endo TA™ and Endo GIA™ laparoscopic stapling devices. There were no
laparoscopic stapling device malfunctions and no vascular complications during the procedures.
Breda, A. et al., Complications of Laparoscopic Living Donor Nephrectomy and Their
Management: The UCLA Experience, UROLOGY 2007;69(1):49-52. This article evaluated a
series of 300 laparoscopic living donor nephrectomies (“LLDN”) performed by a single surgeon
using an unspecified endovascular stapler. Two conversions to open occurred as a result of major
vascular complications: one that the authors attributed to “an endovascular stapler malfunction”
and one to “a Veress needle injury.” The authors reported no patients deaths or post-operative
bleeding complications, other than one subcutaneous hematoma. They concluded that “[t]he
results of our series support the safety of LLDN, because the intraoperative and postoperative
complications are very rare.”
Liu, K. et al., Techniques of Vascular Control in Laparoscopic Donor Nephrectomy,
TRANSPLANT PROC 2008;40(7):2342-44. This case series evaluated 33 laparoscopic donor
nephrectomy procedures performed with United States Surgical’s Endo GIA™ stapler and
compared those results to 11 procedures using a polymer locking clip. The authors found that
donor and recipient outcomes were similar no matter whether polymer locking clips or the Endo
GIA™ stapler was used. They reported one stapler malfunction requiring conversion to an open
procedure. There were no deaths reported.
Cresswell, A. et al., Evaluation of Intrahepatic, Extra-Glissonian Stapling of the Right Porta
Hepatis vs. Classical Extrahepatic Dissection During Right Hepatectomy, HPB (OXFORD)
2009;11(6):493-98. This retrospective case-controlled study evaluated two techniques for
colorectal liver metastases in 342 patients. All procedures used Covidien’s Auto Suture™
Endovascular Device. The authors reported two minor bile leaks that were controlled with suture
reinforcement, one of which “may have resulted from operator error as a result of the stapling
device being pushed too firmly onto the portal pedicle and causing the tissue to bunch at the angle
of the gun.” Four persistent bile leaks also were reported. The authors noted two instances of
stapling device failure: in one case the “tissue being stapled was too bulky and the stapling
cartridge was unable to fully deploy,” and in the other “the stapler deployed but locked and could
not be released from the pedicle.” In both cases, bleeding was easily controlled with a vascular
clamp. The authors concluded that the “stapling device was safe and reliable” and noted that
“[t]echnical pitfalls identified from the episodes associated with minor intraoperative
complications include attempting to offer too substantial a tissue load which exceeds the
capabilities of the stapling device.”
Offodile, A. et al., High Incidence of Technical Errors Involving the EEA Circular Stapler: A
Single Institution Experience, J AM COLL SURG 2010;210(3):331-35. This article summarized
data on 349 colorectal resections performed using an unspecified EEA circular stapling device
and compared outcomes from surgeries where a stapler “malfunction” occurred to those with no
malfunction. The authors reported no significant difference in length of stay, reoperation rates,
anastomotic leaks, strictures, and wound infections. There were more gastrointestinal bleeds in
the “malfunction” group (3), consisting of clinical bleeds unrelated to the staple line; more
conversion to open surgery (15); and more frequent need for transfusion (9). Of the
“malfunctions,” two involved primary device failure. No device-related deaths occurred. The
authors concluded that “[a]ll procedures have an inherent risk for complications that is independent
of the devices used;” “[u]ser error, and not a primary device defect, was the most common cause
of stapler malfunction;” and “[o]perator experience is critical not only for recognizing stapler
problems but also for correcting and even pre-empting them.”
Seshadri, R. et al., Modified Technique of Stapled Esophagojejunostomy Without a Purse-
String Suture, INDIAN J SURG ONCOL 2011;2(3):189-92. This article reported outcomes from 35
cases in which stapled esophagojejunostomy was performed without using a purse-string suture.
The procedures utilized Ethicon’s Proximate ILS™ circular stapler. The authors reported that they
experienced one stapler “malfunction” and had no anastomotic leaks. They concluded that
“stapled esophagojejunostomy without a purse-string suture makes the procedure more easy, safe
and simple.”
Gonzalez Valverde, F. et al., Frequency and Causes of Conversion from Laparoscopic to Open
Roux-en-Y Gastric Bypass for Morbid Obesity: The Experience in Our Service, OBES SURG
2013;23(3):391-92. This article examined a series of 200 laparoscopic Roux-en-Y gastric bypass
procedures, reporting on the rate of conversion to open procedure. According to the authors, 3%
of the procedures were converted to open. One of those conversions was related to anastomotic
leak “due to a EEA stapler malfunction.” The authors did not identify the specific type of stapler
used.
Raoof, M. et al., Morbidity and Mortality in 1,174 Patients Undergoing Hepatic Parenchymal
Transection Using a Stapler Device, ANN SURG ONCOL, 2014;21(3):995-1001. This article
provided a retrospective review of 1,174 cases of hepatic parenchymal transection. Across the
1,174 cases, there were 13 instances of “misfired” staples, and these patients had higher blood loss
and mortality. The specific types of staplers used were not identified. Based on their review, the
authors concluded that “[u]se of stapler device for hepatic resection is safe and effective.”
Ouchi, A. et al., Staple-line Recurrence Arising 10 Years After Functional End-to-End
Anastomosis for Colon Cancer: A Case Report, SURG CASE REP 2015;1(1):7. The authors
reported on a single patient who had a staple-line recurrence of his colon cancer ten years after his
original resection which involved a Covidien Endo GIA™ stapling device. The authors concluded
that “[c]onsideration of staple-line recurrence and careful work-up is important when patients with
FEEA for colon cancer complain of any digestive organ symptoms.” The authors did not suggest
that the recurrence was related to the stapler used in the original surgical procedure.
Kuthe, A. et al., Multicenter Prospective Evaluation of a New Articulating 5-mm Endoscopic
Linear Stapler, SURG ENDOSC 2016;30(5):1883-93. This prospective, single-arm study evaluated
the safety and efficacy of a novel 5-mm laparoscopic linear stapler (“Cardica MicroCutter”) in
clinical gastrointestinal surgical applications. Unspecified Covidien and Ethicon staplers
(“conventional staplers”) were used to allow for additional comparison of stapler-related adverse
events within study subjects. Conventional staplers were used in 42% of procedures to transect
tissue outside the capable thickness range of Cardica MicroCutter. According to the authors, over
the course of 160 procedures, there were two staple line leaks, five staple line bleeds, and 37
incomplete staple lines. All of these issues were “immediately resolved” and none resulted in
complications. The authors reported that there were thirteen post-operative complications related
to the method of performing the anastomosis, six for conventional staplers (including two staple
line leaks), one related to the Cardica MicroCutter (post-operative bleed), and six related to hand-
sewn anastomosis (including three-post operative bleeds).
Abu-Ghanem, Y. et al., Gastric Wall Thickness and the Choice of Linear Staples in
Laparoscopic Sleeve Gastrectomy: Challenging Conventional Concepts, OBES SURG
2017;27(3):837-43. The authors reported outcomes for 202 patients who underwent laparoscopic
sleeve gastrectomy using a “tight order” of Ethicon’s Echelon FlexTM Endopath ® staples and
cartridges. In the series, the authors noted 3.1% mechanical failures, all of which were resolved
by over-suturing the staple line. The authors reported post-operative bleeding in five patients and
no leaks. The authors concluded that tight stapling is “safe” and does not cause ischemia.
Hsu, T. et al., Presence of Colon Carcinoma Cells at the Resection Line May Cause Recurrence
Following Stapling Anastomosis, ASIAN J SURG 2018;41(6):569-72. This retrospective clinical
study examined the presence of carcinoma cells along colon resection lines. The authors suggested
that cancer cells may get trapped in a double staple-line if the surgeon does not perform
“appropriate irrigation during dissection and clamping to remove cellular debris [which] may
result in the development of local recurrence at the double-staple line.” No specific type of stapler
was identified. The authors also noted that the same phenomenon has been reported in sutured
anastomoses.
Jain, S. et al., This Challenging Procedure has Successful Outcomes: Laparoscopic
Nephrectomy in Inflammatory Renal Diseases, UROL ANN 2018;10(1):35-40. This prospective
study compared different techniques for performing laparoscopic nephrectomy in inflammatory
renal diseases. Covidien’s Multifire Endo GIA™ staplers were used in all of the procedures.
Across 44 procedures, there were two unspecified “vascular stapler malfunctions” but no post-
operative bleeding or need for reoperation. The authors concluded that successful outcomes can
be achieved with a laparoscopic approach, although a learning curve exists in performing the
procedure.
Zhang, B. et al., Left Minimally Invasive Esophagectomy in a Patient with Synchronous
Esophageal and Lung Cancers: Case Report, MEDICINE (BALTIMORE), 2018;97(2):e9173. The
authors reported a single patient who had a successful esophagectomy for esophageal and lung
cancer via a left minimally invasive approach. The procedure utilized an unspecified linear
endostapler. There were no intra- or post-operative complications.
EXHIBIT B
MEDTRONIC AD COM SLIDES
GENERAL & PLASTIC SURGERY DEVICES ADVISORY COMMITTEE MEETINGMay 30, 2019
INTRODUCTION & OVERVIEW OF INTERNAL SURGICAL STAPLERSJohn de Csepel, M.D.
Chief Medical Officer & Vice President, Medical Affairs
Minimally Invasive Therapies Group, Medtronic
3 FDA Advisory Committee Meeting | May 30, 2019KEY POINTS Medtronic surgical staplers have a well-established safety profile
Complaint rates for our staplers have been low and stable:
– Most complications are related to the underlying surgical procedure,
patient comorbidities, and manner of use
– Medtronic mitigates these risks through labeling, training, and innovation
Medtronic supports reclassifying internal staplers as Class II devices and
implementing clinically relevant special controls
4 FDA Advisory Committee Meeting | May 30, 2019AGENDAOverview of Surgical Staplers John de Csepel, M.D.Chief Medical Officer & Vice President, Medical Affairs
Minimally Invasive Therapies Group, MedtronicSafety & Performanceof Medtronic Staplers Sam Ajizian, M.D.Vice President, Medical Safety
Minimally Invasive Therapies Group, MedtronicComments on FDA’s Proposed Guidance John de Csepel, M.D.Chief Medical Officer & Vice President, Medical Affairs
Minimally Invasive Therapies Group, Medtronic
5 FDA Advisory Committee Meeting | May 30, 2019SURGICAL STAPLERS HAVE REVOLUTIONIZED SURGICAL PRACTICE DECREASE SURGEONVARIABLILITY AS COMPAREDTO HAND SUTURINGENABLE MORE COMPLEX SURGICAL PROCEDURES INCLUDING MIS AND LAPAROSCOPY Standard practice in a variety of surgical procedures Used in millions of surgeries each yearDECREASE TIME SPENT IN THE O.R.
6 FDA Advisory Committee Meeting | May 30, 2019MEDTRONIC HAS BEEN AT THE FOREFRONT OF STAPLING INNOVATION1960s 1970s 1980s 1990s 2000s 2010s1STU.S. SURGICAL STAPLER 1STLAPAROSCOPICSTAPLER 1STPOWEREDSTAPLERCURRENTLY MARKET 23 SURGICAL STAPLERS – ALL SUBMITTED AS CLASS II DEVICES
7 FDA Advisory Committee Meeting | May 30, 2019MEDTRONIC CONDUCTS EXTENSIVE PRE-CLEARANCE TESTINGSTABILITY Accelerated aging testing conducted to support the labeled shelf life of single use devicesSTERILITY ASSURANCE Testing conducted in accordance with industry standardsBIOCOMPATIBILITY Testing conducted in accordance with industry standards and FDA GuidanceSAFEFTY & PERFORMANCE In Vitro Staple formation Anvil attach force Anvil detach force Firing force In Vivo
Adjacent tissue trauma Hemostasis Staple formation Knife cut Staple line strength Radiographic / CT verification of staple line Ex Vivo
Staple line strength Across staple line firingUSABILITY Usability evaluation conducted following international standards to demonstrate that devices meet product design specifications by:
Validating Instructions for Use and training Validating potential use error per Risk and Hazard analysis Evaluating device performance per design specifications
8 FDA Advisory Committee Meeting | May 30, 2019MEDTRONIC CONDUCTS ADDITIONAL TESTING ON OUR POWERED STAPLERSELECTRICAL SAFETY Pre-clearance testing is conducted in accordance with international standardsSOFTWARE VERIFICATION & VALIDATION Full software verification and validation is performedCLEANABILITY / REPEATED STERILIZATION Devices are repeatedly soiled, cleaned, re-sterilized, and tested to ensure performanceRELIABILITY / CYCLICAL TESTING Performance of reusable devices is measured and monitored over several cycles to calculate the appropriate life of the device
9 FDA Advisory Committee Meeting | May 30, 2019MEDTRONIC HELPS MITIGATE INHERENT RISKS THROUGH LABELING, TRAINING, AND INNOVATIONLabeling Appropriate stapler use and staple selection
Relevant contraindications, warnings, and precautionsTraining Lectures
Surgical simulations
Case observations
Support for fellowship and medical society training programsInnovation Help make stapling easier and more consistent for surgeons
SAFETY & PERFORMANCEOF MEDTRONIC SURGICAL STAPLERSSam Ajizian, M.D.
Vice President, Medical Safety
Minimally Invasive Therapies Group, Medtronic
11 FDA Advisory Committee Meeting | May 30, 2019MEDTRONIC MONITORS SAFETY OF STAPLERS THROUGH A ROBUST QUALITY SYSTEM ADVANCED DESIGNAND MANUFACTURINGCONTROLS POST-MARKET VIGILANCE TEAMDoctors, Nurses,
and Engineers
INVESTIGATE AND REPORT COMPLAINTSTO THE FDA
12 FDA Advisory Committee Meeting | May 30, 2019HOW WE EVALUATE CUSTOMER COMPLAINTSFDA defines a complaint as “any written, electronic, or oral communication that
alleges deficiencies related to the identity, quality, durability, reliability, safety,
effectiveness, or performance of a device after it is released for distribution.”
Complaints come from many different sources Complaints vary significantly in content, information, and types of product issues Without context, the number of reported complaints does not provide reliable information regarding performance or safety THE VAST MAJORITYOF COMPLAINTSDO NOT RELATE TO A PATIENT INJURY
13 FDA Advisory Committee Meeting | May 30, 2019ALL COMPLAINTS ARE THOROUGHLY INVESTIGATED BY PMV TEAM AND MEDICAL SAFETY PERSONNELPost-Market Vigilance Investigation Collection and analysis of information
Review of manufacturing history, complaint history, and other relevant
data
Device testing (if available)
Goal is to identify root cause and, when appropriate, implement corrective
actionMedical Safety Investigation Parallel investigation of all serious injury and death complaints
Includes interviews with clinical personnel and review of medical history
Provides an independent assessment of the complaint
14 FDA Advisory Committee Meeting | May 30, 2019MEDTRONIC SUBMITS COMPLAINTS TO FDA IN ACCORDANCE WITH FDA REGULATIONS MEDTRONICREPORTABLE STAPLING COMPLAINTSALL MEDICALDEVICE REPORTS2001-2017 MALFUNCTIONSSERIOUS INJURIES AND DEATHS FDAFDA’SASRPATHWAY(BATCH) FDA’SSTANDARDREPORTINGPATHWAY(INDIVIDUAL) MEDTRONIC RESUMED SUBMITTING ALL COMPLAINTS AS INDIVIDUAL MDRs IN 2017
~2 MDR REPORTS PER EVERY 1 COMPLAINT OVER THE LAST 2 YEARS15 FDA Advisory Committee Meeting | May 30, 2019MEDTRONIC OFTEN SUBMITS MULTIPLE REPORTS FOR A SINGLE COMPLAINT = 2 REPORTSIN MAUDEDATABASE1 PATIENT COMPLAINT STAPLERHANDLEREPORTSTAPLERRELOADREPORT2 MDRS
16 FDA Advisory Committee Meeting | May 30, 2019COMPLICATIONS WITH MEDTRONIC INTERNAL SURGICAL STAPLERS ARE RARE COMPLICATIONS ARE AN INHERENT RISK OF ALL SURGICAL PROCEDURES COMPLEX PROCEDURESAND/ORHIGH-RISK PATIENTS STAPLING COMPLAINTRATES ARE LOW
17 FDA Advisory Committee Meeting | May 30, 2019OVERALL REPORTABLE COMPLAINT RATES 0.00%0.01%0.02%0.03%0.04%0.05%0.06%0.07%0.08%0.09%0.10%01000200030004000500060007000 2011 2012 2013 2014 2015 2016 2017 2018 2019C
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)RatesCOMPLAINT RATES RANGE FROM 0.06%-0.10%Note: Analysis excludes duplicate reports
18 FDA Advisory Committee Meeting | May 30, 2019REPORTABLE COMPLAINTS INVOLVING DEATH 0.00000%0.00005%0.00010%0.00015%0.00020%0.00025%0.00030%0.00035%0.00040%051015202530 2011 2012 2013 2014 2015 2016 2017 2018 2019C
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)RatesCOMPLAINT RATES RANGE FROM 0.0002%-0.0005%BACKGROUND SURGICAL MORTALITY RATES RANGE FROM 0.2%-2%11. Healey, M. et al 2002; Heeney, A. et al 2014; Ingraham, A. et al 2011; Tevis, S. et al 2013; Weiser, T. et al 2Note: Analysis excludes duplicate reports
19 FDA Advisory Committee Meeting | May 30, 2019REPORTABLE COMPLAINTS INVOLVING SERIOUS INJURY 0.000%0.002%0.004%0.006%0.008%0.010%0.012%0.014%0.016%0.018%01002003004005006007008009001000 2011 2012 2013 2014 2015 2016 2017 2018 2019C
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)RatesSerious InjuryCOMPLAINT RATES RANGE FROM 0.008%-0.017%BACKGROUND RATES OF SURGICAL COMPLICATIONS RANGE FROM 5%-15%11. Tevis, S. et al 2013; Ingraham, A. et al 2011; Healey, M. et al 2002Note: Analysis excludes duplicate reports
20 FDA Advisory Committee Meeting | May 30, 2019REPORTABLE COMPLAINTS INVOLVING MALFUNCTION 0.00%0.01%0.02%0.03%0.04%0.05%0.06%0.07%0.08%0.09%0100020003000400050006000 2011 2012 2013 2014 2015 2016 2017 2018 2019C
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)RatesMalfunctionCOMPLAINT RATES RANGE FROM 0.05%-0.09% Note: Analysis excludes duplicate reports
21 FDA Advisory Committee Meeting | May 30, 2019SAFETY AND PERFORMANCE SUMMARY No new safety signals across our stapler portfolio
Stapler complaint rates low and stable when accounting for ASR
Serious injury complaint rate declined by ~50%
Most complaints relate to the inherent risks of the surgical
procedure,
patient comorbidities, or the manner in which the device is used
FDA’S RECLASSIFICATION & DRAFT LABELINGGUIDANCEJohn de Csepel, M.D.
Chief Medical Officer & Vice President, Medical Affairs
Minimally Invasive Therapies Group, Medtronic
23 FDA Advisory Committee Meeting | May 30, 2019MEDTRONIC SUPPORTS THE FDA’S EFFORTS TO ENHANCE THE SAFE USE OF SURGICAL STAPLERS Medtronic supports reclassifying all staplers as Class II devices,
consistent with our own practice
Medtronic supports FDA’s effort to standardize controls for all
staplers
– Further discussion needed regarding specifics and extent to which
controls
are relevant to established devices
24 FDA Advisory Committee Meeting | May 30, 2019PROPOSED PRE-CLEARANCE TESTING FDA’s proposed pre-clearance testing is generally consistent with
our current practices
Additional discussion is needed to fully evaluate the proposal, in
particular around established devices
Special controls should be clinically relevant and should help
enhance safe use
Powered staplers should be addressed in special controls
25 FDA Advisory Committee Meeting | May 30, 2019PRODUCT LABELING Product labeling contains accurate and appropriate information
regarding our staplers
We support the FDA’s proposal to update internal stapler labeling to
further increase physician awareness and enhance safe use
– Focus on information that is clinically relevant and helpful to surgeons
– Does not interfere with clinical decision-making
26 FDA Advisory Committee Meeting | May 30, 2019CONCLUSION: RESPONSES TO FDA QUESTIONSQUESTION #5: We agree that internal staplers should be treated as Class II devices, consistent with our own practiceFDA QUESTION MEDTRONIC RESPONSEQUESTION #1: We generally agree that FDA’s list reflects the risks associated with use of internal staplers, with the exception of cancer recurrence Many of these are inherent risks of the surgical procedure, attributable to patient comorbidities, and/or relate to the manner of useQUESTION #2: The available data provides strong evidence of clinical safety and effectivenessQUESTION #3: FDA’s list is a productive starting point Questions remain as to the specifics and relevance to devices that have been in clinical use for years Further discussion between FDA and manufacturers is needed to work out details and to ensure that all controls are clinically relevantQUESTION #4: We agree that special controls should be required for internal staplers Our internal staplers do not present an unreasonable risk of injury
QUESTIONSANDANSWERS
EXHIBIT C
PROPOSED TESTING CONTROLS CHART
FDA Proposed Special Controls vs. Current Medtronic Protocol
FDA Proposed Special Controls Type of Testing Current Medtronic Protocol
“[S]helf-life testing must demonstrate that the device maintains its performance characteristics and the packaging of the device maintains its integrity for the duration of the proposed shelf-life.”22
Stability Testing
Stability testing conducted to support the labeled shelf life of the devices.
“Additionally, because the risk of infection can arise from a contaminated device, sterility testing must demonstrate the sterility of the device.”23
Sterilization Validation
Conducted in accordance with ISO 11135-1 and ISO 10993-7.
“FDA believes that the device must be demonstrated to be biocompatible because the risk of adverse tissue reaction may result from contact of the materials of the device with the body.”24
Biocompatibility
Testing
Conducted in accordance with ISO 10993-1 and FDA Guidance, Use of International Standard ISO 10993-1, dated June 16, 2016.
“FDA believes that adequate performance testing must include an evaluation of staple formation characteristics in the maximum and minimum tissue thicknesses for each staple type; measurement of the worst-case deployment pressures on stapler firing force; and a measurement of staple line strength.”25 “Performance testing must also demonstrate confirmation of staple line integrity (e.g., through the absence of vertically contiguous malformed staples), as well as in vivo confirmation of staple line hemostasis following staple deployment.”26 “Examples of key performance parameters include information on firing the stapler, such as the firing force, pre-fire compression time, and maximum number of consecutive firings, and information relevant to creating a staple line, such as the percentage of properly formed staples, number of incremental firings required to complete a
Performance Bench Testing
In Vitro
• Staple formation • Firing force • Reliability testing for reusable
staplers
In Vivo • External atraumatic tissue • Hemostasis • Pneumostasis • Staple formation • Knife cut • Anastomotic and transection burst
pressure • Radiographic / CT scans
Ex Vivo Animal Testing
• Burst testing • Staple formation when fired
across intersecting staple lines
22 84 Fed. Reg. 17116, at 17121. 23 Id. 24 Id. 25 Id. 26 Id.
FDA Proposed Special Controls Type of Testing Current Medtronic Protocol staple line, and maximum number of reloads.”27
“Usability testing and a labeling comprehension study must demonstrate that the clinician can correctly select and use the device for its indicated use based on the information in the labeling.”28
Human
Factors/Usability
Conducted in accordance with FDA Guidance, Applying Human Factors and Usability Engineering to Medical Devices, dated February 3, 2016. Usability evaluation conducted following IEC 60601-1-6 and IEC 62366-1 to demonstrate that the subject devices meet product design specifications by:
• validating Instructions for Use (IFU) and training
• validating potential use error per Risk and Hazard analysis
• evaluating device performance per design specifications
“If any components of the device are reusable, the labeling must include validated methods and instructions for cleaning and sterilization of these reusable components. Validation of cleaning and sterilization instructions must demonstrate that any reusable device components can be safely and effectively reprocessed per the recommended cleaning and sterilization protocol in the labeling.”29
Reprocessing
Validation
Conducted in accordance with FDA Guidance, Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling, dated March 17, 2015, and subsequently updated on June 9, 2017.
27 Id. 28 Id. 29 Id.
EXHIBIT D
UNOFFICIAL AD COM TRANSCRIPT
1
General and Plastic Surgery Devices Panel 1
Meeting Date: 5/30/19 2
3
LEWIS: Good morning. I would like to call the meeting of the panel to order. This is 4
the FDA's Center for Devices and Radiological Health and Plastic Surgery Devices Panel 5
for the Medical Devices Advisory Committee. 6
7
It's now 9:15. I'm Dr. Frank Lewis, the chair of the Panel. I am general surgeon with 8
most of my experience in trauma and critical care. And I was the executive director of 9
the Board of Surgery for 15 years before retiring about one year ago. 10
11
I would like to note for the record that the members who are here present as a quorum are 12
required by FDA regulations to participate in FDA Device Law and Regulations Training 13
and all have done so. 14
15
For today's agenda, the Committee will discuss and make recommendations regarding the 16
reclassification of surgical staplers under the classification GAG and staplers GDW, 17
which are already classified as Class II, GAG is classified as Class I. 18
19
These devices are considered pre-amendment devices since they were in commercial 20
distribution prior to May of 1976 when the medical devices amendments became 21
effective. 22
23
Before we begin, I would like to go around the panel and ask our distinguished panel 24
members and FDA staff here at the table to introduce themselves. Please state your 25
name, your area of expertise, your position and your affiliation. 26
27
Why don't we start to the left with Ms. Pawelski. 28
29
PAWELSKI: Thank you. Lynn Pawelski, Vice President of Global Regulatory Affairs 30
at Baxter Healthcare. I'm the industry representative on the panel. 31
32
POSNER: Phil Posner, retired medical science at University of Florida, FSU, and 33
Auburn and -- actually former instructor in 1960 in surgery at SUNY Downstate. 34
35
LEWIS: Thank you. Ms. Brummert? 36
37
BRUMMERT: Rachel Brummert, I'm with Charlotte-Mecklenburg Police Department. 38
I'm the consumer representative. 39
40
PORIES: Walter Pories, Professor of Surgery and Biochemistry, Director of Medical 41
Surgery Research Group at East Carolina University. And most of my practice is 42
bariatric surgery. 43
2
44
HICKS: I'm Terry Hicks. I'm the associate chair of the Department of Colon and Rectal 45
Surgery at the Ochsner Clinic in New Orleans. And I have spent most of my life in the 46
practice in the last 35 years in colon and rectal surgery. 47
48
GARCIA: Commander Patricio Garcia, I'm the designated federal officer for this 49
meeting today. 50
51
BLOOM: Matthew Bloom, the trauma and general surgery at Cedars-Sinai, Los Angeles. 52
53
MILLER: I'm Mike Miller. I'm a plastic surgeon. I'm in private practice in Denver. As 54
of two months ago, I'm sure many years (ph) I was the chair of plastic surgery at Ohio 55
State University. 56
57
KRUPNICK: Alexander (ph) Krupnick, I'm a thoracic surgeon at University of Virginia 58
and vice chairman of the department. 59
60
MEURER: Will Meurer, I'm in the Department of Emergency Medicine and Neurology. 61
My work focuses on clinical trials and evidence synthesis. 62
63
LEVY: Elliot Levy, I'm a staff clinician and interventional radiologist at the National 64
Institutes of Health. 65
66
KRAUS: Good morning. My name is David Kraus. I'm a cell biologist. I'd like to say 67
thank you to all of you for being here and helping us out on this issue. 68
69
I'm currently the deputy director of the office of Surgical and Infection Control Devices 70
and I'm the acting division director for the Division of Infection Control and Plastic 71
Surgery Devices. 72
73
LEWIS: Thank you all. Members of the audience, if you've not already done so, we 74
urge you to sign the attendance sheets that are on the table just outside the door as we 75
(ph) have a chance. We'll now turn to Commander Patricio Garcia, the designated federal 76
officer for this meeting, who will make some introductory remarks. 77
78
GARCIA: Thank you, Dr. Lewis and good morning, everyone. I will now read the 79
conflict of interest statement particular manner (ph) of general applicability. 80
81
The Food and Drug Administration is convening today's meeting of the General and 82
Plastic Devices Panel of the Medical Devices Advisory Committee under the authority of 83
the Federal Advisory Committee Act of 1972. With exception of the Industry 84
Representatives or representative, all members and consultants of the Panel's special 85
government employees or regular federal employees from other agencies and are subject 86
to Federal conflict of interest laws and regulations. 87
88
3
The following information on the status of this Panel's compliance with Federal ethics 89
and conflict of interest laws covered by, but not limited to, those found in 18 U.S.C. 90
Section 208 are being provided to participants in today's meeting and to the public. 91
92
FDA has determined that members and consultants of this Panel are in compliance with 93
Federal ethics and conflict of interest laws. Under 18 U.S.C. Section 208, Congress has 94
authorized FDA to grant waivers to special Government employees and regular Federal 95
employees who have financial conflicts when it is determined that the Agency's need for 96
a particular individual's services outweighs his or her potential financial conflict of 97
interest. 98
99
Related to the discussions of today's meeting, members and consultants of this Panel who 100
are special Government employees or regular Federal employees have been screened for 101
potential financial conflicts of interest of their own as well as those imputed to them, 102
including those of their spouses or minor (ph) children and for purposes of 18 U.S.C. 103
Section 208, their employers. 104
105
These interests may include investments, consulting; witness, expert, testimony, 106
contracts/grants/CRADAs; teaching/speaking/writing; patents and royalties; and primary 107
employment. 108
109
For today's agenda, the Panel will discuss and make recommendations regarding 110
reclassification of surgical staplers for internal use from Class I to Class II for special 111
controls. Based on the agenda for today's meeting, all financial interests reported to the 112
panel -- by the panel members and consultants, no conflict of interest waivers have been 113
issued in accordance with 18 U.S.C. Section 2018. 114
115
Lynn Pawelski is serving as an industry represented -- representative, acting on behalf of 116
all related industry. She's employed by Baxter Healthcare Incorporated. 117
118
We would like to remind members and consultants that if -- the discussion involves any 119
other products or firms not already on the agenda for which an FDA participant has 120
personal or impute the financial interest. The participant needs to exclude themselves 121
from such involvement and their exclusion will be noted for the record. 122
123
FDA encourages all other participants who advice the panel of any financial relationships 124
they may have with any firm at issue (ph). A copy of the statement will be available for 125
review at the registration table during this meeting and will be included as part of the 126
official transfer. Thank you. 127
128
Based on the -- and based on the agenda for today's meeting, all financial interest 129
reported by the Panel members and consultants, no conflict of interest waivers have been 130
issued, according (ph) with 18 U.S.C. Ms. Lynn Pawelski serving (ph) as an industry 131
represented acting on behalf of all the related industry (ph). She's employed by Baxter 132
Healthcare in Deerfield, Illinois. 133
4
134
Before I turn this meeting back over to Dr. Lewis, I would like to make a few general 135
announcements. Transcripts of today's meeting will be available from Free State Court 136
Reporting Incorporated. Information on purchasing videos of today's meeting can be 137
found on the table outside the meeting room. 138
139
Press contact for today's meeting is Ms. Stephanie Caccomo. I would like to remind 140
everyone that members of the public and the press are not permitted in the Panel area, 141
which is the area behind the speaker's podium. I request that reporters please wait to 142
speak to FDA officials until after the Panel meeting has concluded. 143
144
If you're representing in the open public hearings today and have not previously provided 145
an electronic copy of your slide presentation to FDA, please arrange to do so with Mr. 146
Arthur Mela (ph) at the registration desk. In order to help the transcriber identify who is 147
speaking, please be sure to identify yourself each in every time you speak. Finally, 148
please silence your cellphone and other electronic devices at this time. 149
150
Thank you very much. Dr. Lewis? 151
152
LEWIS: I would like now to introduce Ms. Marjorie Shulman, Director of the Premarket 153
Notification Program 510(k) at the FDA, who will be providing a reclassification 154
overview to the panel. And after Ms. Shulman's presentation as well as all others this 155
morning, the Panel will have an opportunity to ask any clarifying questions which are 156
needed. So, please make notes during the presentations in order to do that. Ms. 157
Shulman? 158
159
SHULMAN: Good morning. My name is Marjorie Shulman. I am the Assistant 160
Director of the 510(k), 515(g), Device Determination (ph) De Novo Custom Devices 161
Lifecycle Team. Quite a title. Today, I'm going to give a little background on why we’re 162
here today for the panel meeting. 163
164
So, the purpose is to provide input to the FDA on the classification of surgical staples -- 165
staplers and for internal use and absorbable collagen-based hemostatic devices and 166
whether FDA should reclassify or maintain them in Class I and Class III respectively. 167
168
So, what are the device classes? The classification is based on the controls necessary. 169
Class I is general controls, Class II is general and special controls, and Class III is 170
premarket approval. And the goal is the device should place in the lowest class whose 171
level of control provides reasonable assurance of safety and effectiveness. 172
173
So, what are the general controls? They include such things as prohibitions against 174
adulterated and misbranded devices, good manufacturing practices, registration of the 175
manufacturing facilities, listing of the device types that are made there, record keeping, et 176
cetera. 177
178
5
A special control includes such things as performance standards, postmarket surveillance 179
and patient registries. There's also a Class I devices for Class I or II devices that general 180
controls are sufficient to provide reasonable assurance of safety and effectiveness. 181
Typically, Class I devices do not require premarket notification and their exempt also 182
some from -- some many quality system regulations, also known as the design (ph) 183
controls. 184
185
Also Class I devices are for devices that cannot be classified into Class III because they're 186
not life-supporting or life-sustaining or substantial importance in preventing impairment 187
of public health and because they do not present an unreasonable risk of illness or injury, 188
and they can't be classified in Class II because insufficient information exists to establish 189
special controls to provide reasonable assurance of safety and effectiveness. 190
191
So, what are some examples of Class I devices? Elastic bandages, examination gloves, 192
adhesive bandages, and crutches. Class II devices or for devices that can't be classified 193
into Class I because the general controls that we just spoke about are insufficient to 194
provide reasonable assurance of safety and effectiveness of the device and there is 195
sufficient information to establish special controls to provide such assurance. And Class 196
II devices typically require premarket notification 510(k) prior to be marketed. 197
198
So, some examples of Class II devices powered muscle stimulators, some medical lasers, 199
endoscopes. 200
201
So, how are the special controls used? So for an example, the percutaneous transluminal 202
coronary angioplasty, PTCA, catheters were reclassified from Class III to Class II into 203
special controls. FDA issued the special control guidance document to mitigate the risk 204
to health and it included such things as required by comparability, testing, performance 205
testing, animal testing, clinical information, sterilization, and shelf life. It also had a part 206
in labeling for the warnings, precautions, and adverse effects, et cetera. 207
208
These special controls in combination with the general controls provide a reasonable 209
assurance of safety and effectiveness, and the companies must provide evidence in their 210
510(k) submission of how the special controls were addressed. 211
212
Class III is for devices that can't be classified into Class I or III because insufficient 213
information exists to determine that the general controls and the special controls are 214
sufficient to provide reasonable assurance to the safety and effectiveness and the devices 215
are life-sustaining and/or life supporting of substantial importance in preventing 216
impairment to human health or present an unreasonable risk of illness or injury. 217
218
Class III devices typically require premarket approval also known as PMA prior to being 219
marketed. 220
221
Some example of Class III devices, breast implants, dermal fillers, and implanted 222
neurostimulators. 223
6
224
So, what is the reclassification process? In order to reclassify the device, FDA must 225
propose a pro -- publish a proposed order announcing their (ph) proposed classification 226
and seek public comment. Hold a panel meeting. If classified or reclassifying the device 227
type and consider all comments and available information, including the panel 228
recommendation prior to issuing an administrative order finalizing the classification of 229
the device. 230
231
So, this is just the flow chart to help you out of needed, it goes through the general 232
controls, special controls and if you follow the flowchart, what we talked about for Class 233
I, II and III. 234
235
So what do we need from the panel today? We would like your input on the 236
classification of the device that are subject at the panel sessions and the input should 237
include an identification of the risk to health, if any, presented by the device, whether the 238
device is life-sustaining or life supporting or substantial importance in preventing the 239
impairment to human health or presents an unreasonable risk of illness or injury. 240
241
Whether sufficient information exist to develop special controls, the identification of 242
those special controls and whether the general controls alone are sufficient. 243
244
After the panel meeting, FDA will consider the available evidence including the input of 245
this panel and public comments. And if we have not already done so, FDA will issue a 246
proposed order, proposing reclassification of the devices and seeking comment, and then 247
FDA may issue an administrative order identifying the appropriate class. 248
249
Thank you. Any questions? 250
251
LEWIS: Are there any questions from the panel? Yes, sir? 252
253
UNKNOWN: I just wonder, who initiates reclassification procedure? Does that start 254
with the FDA or does that start with a particular applicant? 255
256
SHULMAN: It can be anyone who can initiate it. It can be any interested person or it 257
can be the FDA to initiate it. 258
259
UNKNOWN: I have two questions, Ms. Shulman. The first I would ask you is, could 260
you give the panel members some detail in regard to what is in involved in the 510(k) and 261
what specifics have to be followed? 262
263
SHULMAN: Sure, a 510(k) is where a company is going to claim equivalents to illegally 264
marketed device or if it's a reclassified device, we're going to look at the special controls 265
that were associated with the device. We're going to get the information in an application 266
into the FDA. The company is going to give us the test results what was done to show 267
7
equivalents or to meet the special control for the guidance (ph) document. And we're 268
going to review that information and determine if it's substantially equivalent. 269
270
UNKNOWN: OK. The second question is, it's my understanding that the staplers or a 271
Class I device, but the state balls (ph) are Class II device. Since one cannot be used 272
without the other, how does the FDA in fact manage that dichotomy currently? 273
274
SHULMAN: So, we're going to get into that further in the panel meeting and that will be 275
the discussion that will be presented in a little bit. 276
277
LEWIS: Yes, Dr. Garcia? 278
279
GARCIA: Could you just clarify for me the process after, say, PTCA or something is 280
passed and it's being utilized, what is the real world relationship between the FDA in 281
their reporting of complications? Do you off – you know, are (ph) they required at a 282
certain amount of time to send it to you so you can follow it up? How does that work? 283
284
SHULMAN: I'm sorry, I'm a little bit confused with (ph) the question. Are you talking 285
about … 286
287
GARCIA: Let's just take … 288
289
SHULMAN: … like after? 290
291
GARCIA: Let's just take, for example, a stapler. I will give you a stapler, FDA passes it, 292
said you can use it. The problems that occur, the complications that occur with that 293
stapler over time, is there a relationship where I'm required, as a stapler company (ph), to 294
give you every six months, every year a report of the complications that occurred with 295
this? 296
297
SHULMAN: Right. There is medical device reporting and adverse events should be 298
reported to the MDR, of course (ph) in the Medical Device Reporting and that's how 299
that’s tracked. I think we're going to discuss that further too. 300
301
GARCIA: Well, do you know how often that occurs? How often am I -- am I required to 302
send you the list of complications that have occurred with utilization of (ph) my 303
instrument? 304
305
SHULMAN: I do not know the exact rules, but I'm sure we do have an expert here who 306
can answer that question on -- (INAUDIBLE) I don’t want to misspeak. 307
308
NAST: Thank you. Hi, I'm Karen Nast. Companies are required to report events of 309
malfunctions, serious injury and death to us within 30 days. 310
311
8
GARCIA: All right. And then, who reviews, where does that go? From you -- it's now 312
on your desk, where does that go to, that information? 313
314
NAST: It is stored in our database and reviewers review it. FDA staff reviews it. 315
316
GARCIA: All right. I just leave you one more quick question, because I was thinking, 317
there’ve been, you know, recent public announcements of recalls on certain staplers that 318
came from the company. If you're looking at this database as it goes along, are you 319
aware, could you look at that and say, look, we're seeing a lot of this problem? Do you 320
have the power and tell them, guys you need to pull this for the moment or relook at it? 321
322
NAST: We have the reports that we (ph) trend and we can work with the companies for 323
whatever action is … 324
325
GARCIA: But if we look at the recent -- I'm just -- don’t want to prolong this but, say, 326
you know, somebody comes up and then they pronounce (ph) they’re not going to give 327
you (ph), this instrument’s being recalled. Some did (ph) misfiring. We’ve had misfires 328
for whatever reason. You had that information on the front end, they have it. I'm just 329
trying to -- is that the point you're making (ph), is it the responsibility of the company to 330
say, we’ve had enough, we're going to pull it for whatever reasons? What doesn’t the 331
FDA do that from your review? Because you're getting this constant inflow of 332
information, I don't understand that. 333
334
MISAWABA (?): Hi, this is Kaptimina Misawaba (ph) and I also have experience (ph) 335
in compliance with the FDA regulated products. So, when we do get the reports, we look 336
at them for trending. And we also -- we also have signal groups, so see what is going on 337
with a particular product. And we make decisions on what to do in terms of recalling the 338
product or also talking to the friends (ph) to see what has changed that is causing the 339
product to malfunction as much as it is. 340
341
GARCIA: OK. I guess I'm just specifically asking, because within this week, a major 342
company has withdrawn one of their staplers, they did it. Why then it comes from the 343
other end? Why -- how much control is really going with the FDA about that, did 344
somebody not notice that before they did? What was the tipping point for the company to 345
say, we're going to pull this instrument? Why wasn't it picked up somewhere else? If 346
you’re keeping all this data, who is looking at it and why and is something done about it? 347
348
MISAWABA (?): So, the areas (ph) at the FDA like the compliance or the district, we 349
collect that information and then we also review it and then make decisions on what to 350
do. So we have to be looking at it and then when we get together and make a decision on 351
what to do about (ph) to recall it, or some -- or to take any kind of enforcement action. 352
So, we do review it. 353
354
LEWIS: Dr. Krupnick? 355
356
9
KRUPNICK: Yeah, hi. I have a question actually as we're talking about it. How do you 357
guys get the data? For example from a personal experience I've had, you know, a handful 358
staple misfires, what I do is call the rep and chew them out. But, I've never reported it to 359
the FDA. Does the rep report it to -- is every staple misfire have to be reported to the 360
FDA? 361
362
MISAWABA (?): So, the reps or the frames (ph) report to the FDA, to the database, 363
where we collect all the MDRs. 364
365
KRUPNICK: So, they have to legally? Because I can guarantee you they're not doing 366
this. 367
368
(OFF-MIC) 369
370
NAST: All events that meet the criteria for a malfunction, serious injury or death, must 371
be reported to us by the companies -- voluntary reporters such as yourself are able to 372
report to us as well through our voluntary reporting program through MedWatch. 373
374
KRUPNICK: So a staple misfire where then as the most (ph), it just falls apart from your 375
eyes where we do it, is not reported to you guys? 376
377
NAST: If it meets the criteria for a malfunction, serious injury or death it must be 378
reported. 379
380
KRUPNICK: Serious injury or death. 381
382
MISAWABA (?): Yeah. And also to answer that, when we do inspect the firms, this is -383
- we also look at the complaints and other malfunction -- malfunctions with the devices. 384
And we also ensure that -- we also look to make sure if firms have reported or the 385
complaints that they deem MDRs to the FDA, and if they have not, we do tell them to do 386
that and we decide them for not reporting. 387
388
LEWIS: Mr. Meurer? 389
390
MEURER: Hello, this is William Meurer, I guess I want to speak on behalf of the 391
transcriptionist. I think Patricio told us, say your name after -- before everything you say, 392
so. Hi, William Meurer. 393
394
When a device is going from one to two, there wasn't really an underlying 510(k). So 395
what is the process when this determination is made, what does -- what do sponsors have 396
to submit with their devices and what's the time period to kind of get them after 397
compliance with that reclassification? 398
399
SHULMAN: Hi, Marjorie Shulman. So, if we go from one to two, we're going to write 400
the special controls and it's probably and replacing the guidance document. And that's 401
10
what the company would abide by. So, all the things that I went through like if we have a 402
biocompatibility, just say if we have sterility, if we have labeling requirements, and that's 403
what they will have to show. As far as, the timing we're going to wait together the 404
comments and then see -- we couldn't just turn around tomorrow and say OK, everyone 405
must submit a 510(k). 406
407
There's going to have to be timing and that will be laid out in the federal register 408
announcement. 409
410
BUCKNER: Hi, this is Rebecca Buckner with FDA. So, as Marjorie said, there is a 411
process and if you look at the proposed order that we put out last in April at the end of 412
April, there is a section that explains exactly what manufacturers would have to do. So, 413
if they previously have the 510(k), so back before they were exempt, they will have one 414
set of requirements. If they don't have a previous 510(k) they'll have another set of 415
requirements. 416
417
We can't readjudicate the 510(k) if it -- if they already have a clearance, but we can 418
confirm that they meet their current special controls. 419
420
And there are timelines set out for that, in the proposed order, those could change in the 421
final order. You know, if we got feedback, the people need more time to comply or we 422
think they could comply faster. But, that is all laid out in the order exactly what each 423
group of individuals would need to do. 424
425
And then at that point, whatever their requirement is, they would need to either submit a 426
new 510(k) or a confirmed compliance with the special controls typically. 427
428
UNKNOWN: Yeah. 429
430
LEWIS: Ms. Brummert? 431
432
BRUMMERT: Rachel Brummert, consumer representative. I know a lot of patients 433
were saying that the MedWatch is either not recording what they're reported to the FDA 434
or they don't know about MedWatch. So, what is the FDA doing to make that more 435
available to patients? 436
437
NAST: Thank you, it’s Carol Nast again. MedWatch is on our website. I think we just 438
had a revamp of our website. It's available that way. We have a medicine program that 439
reaches out to user facilities. We also have our DICE division that does presentations to 440
inform the public. I think it believe (ph) -- medical device reporting as part of what they 441
talk about. 442
443
LEWIS: Thank you all very much. Why don't we move on? I would next like to 444
introduce Dr. Dale Rimmer, who will make some introductory remarks in device 445
descriptions on behalf of the FDA. Dr. Rimmer, will you please take the podium. 446
11
447
RIMMER: Hello. My name is Dale Rimmer, I'm a chemist and a reviewer in the office 448
of Surgical and Infection Control Devices, FDA Center for Devices and Radiological 449
Health. Welcome today's meeting where we will be discussing the regulatory 450
classifications, surgical staplers for internal use. 451
452
The purpose of today's meeting is to obtain the Committee's input on the risks and 453
benefits of surgical staplers for internal use, which are currently regulated as Class I 454
devices and are exempt from FDA review via the 510(k) process. Additionally, the 455
Committee will consider the reclassification of surgical staplers for internal use from 456
Class I exempt to Class II devices. This panel will not consider implantable staplers 457
which are already Class II devices, nor will this Committee consider surgical staplers for 458
external use otherwise known as skin staplers. 459
460
For the purposes of this presentation, we may hear after refer to surgical staplers for 461
internal use as internal surgical staplers, surgical staplers or staplers. A surgical stapler 462
for internal use delivers staples to internal tissues during the surgery. Internal staplers 463
may be manual or powered and then maybe linear, curve, or circular. Internal staplers 464
maybe used in open, minimally invasive and endoscopic surgery, and may be indicative 465
(ph) for use in a wide range of surgical applications. 466
467
At the time of classification in 1988, surgical staplers had been in common use in medical 468
practice for many years. And FDA believed that general controls were sufficient to 469
provide reasonable assurance of the safety and effectiveness of those devices. And 470
currently, surgical staplers for internal use are Class I devices and are not subject to FDA 471
review by pre-market notification before being marketed. In change as the stapler 472
designs do not require new 510(k) submissions. 473
474
FDA proposes to modify the current regulations to designate surgical staplers for internal 475
use as Class II devices subject to pre-market notification and special controls. The 476
proposed special controls will be presented today and the Committee will be asked to 477
provide comments on the special controls. 478
479
Today, you will hear presentations about the safety issues related to surgical staplers and 480
clinical considerations for surgical staplers. You will also hear a summary of medical 481
device reports for surgical staplers and staples. 482
483
Finally, FDA will describe the current review practice for these devices and we discuss 484
the risks, mitigations and special controls the FDA proposes should surgical staplers for 485
internal use be reclassified into Class II. 486
487
Are there any questions? 488
489
LEWIS: Now have a presentation from the Emergency Care Research Institute regarding 490
safety issues related to surgical stapler devices. Dr. Scott Lucas will make this 491
12
presentation on behalf of the ECRI. And Dr. Lucas, since your organization is not part of 492
the FDA and I suspect most of the panel members aren't familiar with it, could you just 493
take a minute and tell us few things about the CRI -- ECRI and how they function? 494
495
LUCAS: Sure. I will. I have my first slide dedicated to an overview, so I will provide 496
that, absolutely. 497
498
LEWIS: Thank you. 499
500
LUCAS: OK. All right, thank you. Good morning, ladies and gentlemen of the panel 501
and the audience. My name is Scott Lucas, I'm Director of Accident and Forensic 502
Investigation for the ECRI Institute. I'm here today to talk about safety perspectives, our 503
safety perspectives on surgical staplers. 504
505
So, first of all, an overview of ECRI Institute, we are a non-profit organization, 506
independent organization and we're focused on the safety and quality and effectiveness of 507
patient care. We do like in essentially three categories, through the technology decision 508
making, patient safety, and having space clinical guidance. And surgical staplers 509
essentially falls under all three of those categories which I'll touch on. 510
511
So, here's the agenda. We've got -- most of the time, I've dedicated to our safety 512
surveillance programs, so you'll see -- you'll hear a little bit more about what we do 513
through that. I'll also discuss a publication that we put out annually called our Top 10 514
Health Technology Hazards. And now I conclude just some a real comments on human 515
factors and usability of surgical staplers. 516
517
So here's our surveillance experience in general. We started in – we were founded in 518
1968 through our device, medical device evaluation program. Shortly thereafter, we 519
began conducting accident investigations for adverse events related medical devices. 520
Since 1971, we established the problem reporting network, that's a user experience, now 521
can report to us, that's free and voluntary. We've been a contractor for a state-wide 522
mandatory reporting system since 2003. And then since 2008, been a federally 523
recognized patient safety organization and we get voluntary reports through that conduit 524
as well. 525
526
So we have thousands of participants funneling information into our organization and 527
over 5 million events in aggregate through these conduits. 528
529
So I'll be discussing some technical issues related to surgical staplers, so just a brief on 530
the anatomy, see in the top-left image, that's a linear stapler and the scopic stapler and 531
briefly had a handle that the user is holding and squeezing and firing and on the distillate 532
(ph) are the cartridge and the anvil and the cartridge houses the staplers -- the staples. 533
And on the right, that's the close-up of that cartridge and that's -- a lot of effort has been 534
in the technology and the advancement of that cartridge and the anvil and that interaction 535
with the tissue. 536
13
537
So it's been advance -- lot of advancements there. You see on the bottom two images that 538
-- those are, the completing products for powered staplers in the industry right now. So 539
this has evolved to a powered device is now technically an electromechanical device, yet 540
the classification has remained the same as Class I for all these devices. 541
542
So, for accident investigation services, we do a couple of different things. One I'm 543
categorizing as performance improvement. Investigations and that's where we've looked 544
at hundreds of staplers coming in for things like gastrointestinal and anastomotic leaks. 545
And so if the hospital's concerned with a certain percentage, we may review those 546
staplers to see if there's any damage associated with the outcomes. 547
548
We perform essentially three full (ph) investigations a year, and that goes back about 25 549
years where a hospital’s compelled to hire us, to contract us to do a full accident 550
investigation and that can be for reasons of severity or its potential litigation, those types 551
of things. 552
553
So, over the last, say, 10 years, we’ve had six fatalities, 15 injuries, and five cases of no 554
injury that may have required some other kind of intervention, but no real injury to the 555
patient. That's in our accident investigation data. And through that we have identified 556
some higher risks uses, you know, things like lobectomy, nephrectomies can be a risk of 557
serious injury or death if something goes -- goes wrong there. So that's an example of the 558
linear staplers. 559
560
Circular staplers, things like GI and anastomotic leaks, that can be a risk of infection. 561
Patient can go undetected, patient can go home and then later a leak is identified and then 562
infection occurs. So, couple of case studies just to put some meat to this. So, this is a 563
laparoscopic nephrectomy, stapling is performed in the renal hilum. It was reported as 564
misfire during the stapling and there was severe bleeding immediately. So it was a 565
conversion to open, the procedure was completed successfully, however, there were 566
complications and the patient died a few days later. 567
568
So, this was sent to us, we examined the stapler, and you could see in the images on the 569
right, first of all, that top-left image, we -- we were able to confirm that the stapler did not 570
completely fire, you could see that by the yellow pushers that push the staple out of the 571
cartridge. And then on the right image with the arrow, there was clear damage to the 572
anvil side, there was the case of the obvious bending and contortion of that anvil surface. 573
574
And then also in mechanical (ph) damage on, we call it the carriage (ph) slots (ph), these 575
linkage (ph) to drive the knife and the staples down the link of the cartridge. So there 576
was obvious damage to the stapler. We look at it more closely and we see some 577
abrasions on the anvil side. So this scenario is consistent with clamping on another 578
instrument or clamping on a clip or something like that before firing. So that's a 579
commonly reported problem when we see that here and that can be serious when it 580
happens. 581
14
582
OK. So that's a linear example. So circular example like an intraluminal (ph) stapler, for 583
example, case (ph) like diverticulitis requiring full sigmoid resection. So in this case a 584
colorectal anastomosis was performed, it was found that there was a clean cut on the 585
descending cone (ph) side of it, but however no staples. So, then -- so that's a missed -- 586
the integrity was not there. 587
588
There were multiple malformed staples in this case, you could see on that middle image 589
on the tape. The staples are supposed to be a nice V shape; they were not. And so, this 590
required a hands sewn (ph) and decide (ph) an estenosis and a temporary diverting 591
ileostomy because of the trauma to the tissue. So that's a kind of an -- that's an example 592
in a GI application. 593
594
And what we're able to show through testing and observation is that, we feel that the 595
anvil was actually on a slight angle prior to firing and because of the tissue inconsistency 596
on the colon. So it was inconsistent density around the colon, we proposed causing an 597
angle on the anvil and a misfire. 598
599
So that's the case where the staples actually contacted the anvil, the center of the anvil, 600
not the wells where they’re supposed to depress and form the V shape. 601
602
So, what's interesting however is, in our cases most of the time when we receive the 603
stapler and we'll fire as designed, as intended, in normal operation, on surrogate tissues. 604
So whatever surrogate tissue we're using in the exemplar testing or begin (ph) some (ph) 605
testing, it will fire normally. So that suggests that there's really something going with the 606
stapler to tissue interaction where we need to focus more of our attention. 607
608
So some select contributing factors include things like jaws clamped on another 609
instruments, which I mentioned, tissue too thick or/the wrong stapler size chosen for that 610
application, wrong vessel, that's obvious. Or some kind of tissue disease or friability, 611
necrosis, et cetera. 612
613
So recurring recommendation includes training a familiarity to our hospitals that contract 614
does for this, with existing and new products. When I say new products, I mean, when 615
there's been, for example a business decision to switch over from one manufacturer to 616
another, there's often complaints associated with that from the users and sometimes 617
familiarity issues and sometimes adverse events related to that transaction. So that can be 618
something that we got to pay attention to. OK. 619
620
So one of our outlets or output from all of this data coming in are what we call our alerts 621
that we publish to, this is directly to our hospital membership and the users of these 622
devices. And we can categorize them as recalls. They can show up in our alerts, or what 623
we call hazard reports, something that we've identified a significant safety issue or 624
hazard. 625
626
15
On the plot to the right, you could see that we put out 42 alerts under this category of the 627
last 10 years. That's not representative of all the reports coming in. That's when we 628
collect and synchronize similar reports and put out a hazard associated with that hazard. 629
630
So common themes include things like, as I've mentioned, incomplete or poor staple line 631
formation, device jaws remaining closed after firing and stuck on the tissue. Other 632
specific hardware she use component breaking, et cetera. 633
634
But -- so this can be minor and require a minor intervention, the patient’s OK, or it can be 635
traumatic. So some notable headlines, you know, use of (ph) thoracic procedures may 636
resolve in serious injury or death. Incorrect stapler size partridges may injure patients, 637
and uncut washers malformed staplers may occur comprising staple line integrity, so all 638
those can have devastating consequences. 639
640
There had been recent recalls as we've already mentioned in the opening statements of the 641
panel, but fund the Medtronic and Ethicon side. So sometimes -- these sometimes do 642
result in recalls and voluntary recalls from the manufacturer if there's been a trend 643
observed on the manufacturing side or from equity (ph) or FDA as we've discussed. 644
645
And so, that leads us to the patient's safety organization. So this is where we have a 646
tremendous amount of data flowing in. These are members of our organization and I 647
wanted to look at about a hundred thousand events into the database. And those are 648
related to surgery and device. So of those, about 2 percent involved staplers so that kind 649
of gives you an order of magnitude, common reports are things like misfire, malfunction 650
as we've seen in the MDR, and laparoscopic is more common. So we're talking about the 651
right stapler here with the internals. 652
653
On the right, you could see the pie chart distribution of harm scores as our MCC, the 654
harm score designation was just a taxonomy that we use in our PSO (ph). And that 655
ranges from A through I where A is no injury and I is death. We've seen up to F in this 656
database, so an F, I'll just read it, an error occurred that may have contributed to or 657
resulted in temporary harm to the patient or required initial or prolonged hospitalization. 658
And there's a continuum from that to A. 659
660
And these are voluntary by the way, and like I said the fatal cases or the serious injury 661
cases are reported to manufacturer, and if it's fatal, directly to the FDA. 662
663
So because of this surveillance and the reports that have come in, we've identified 664
staplers on our top 10 technology hazards list twice, once in 2010 and then again in 2017. 665
And this is -- when we place an item or technology on this list, we think about reports 666
that we've received. We know that there are serious injuries or deaths associated with the 667
use of these devices, or it has potential to do so. We consider insidiousness potentially 668
the depth and the breadth of the problem, and then we collectively have a decision to put 669
it on the list. 670
671
16
So key hazard recommendations in these documents, these are available, the references 672
on the bottom of the slide, user familiarity, having a range of stapler cartridge sizes 673
available. So use recommendations. Appreciating the intra and inter patient tissue 674
thickness variability. So that’s kind of a mouthful, but understanding that not all tissue is 675
the same. So and if we do have an event, it can be -- it can catastrophic and when we do 676
have a remediate measures ready to go, such as alternative means of closure are readily 677
available. 678
679
OK, so just couple comments on human factors and usability. Just a quick review of the 680
510(k), summaries and on staples which have included staplers as part of that . We’ve -- 681
I mean historically has been the focus on, they've been focus on performance testing, 682
substantial equivalence (ph) to predicate devices. 683
684
In 2017, we started seeing some discussion on usability for the staplers. So for example, 685
validating the potential use error per (ph) risk and hazard analysis is important, the 686
training and instructions for use. So there's a lot emphasis on training, instruction for use 687
and labeling associated with these devices. Now, not popping up sort ahead in the right 688
direction. 689
690
And we know that staple line integrity is a function of many things. I mean user 691
experience in training short. The stapler and the cartridge selection and condition, yes 692
that's true as well and the tissue condition as well. So it’s multifactorial that is going into 693
this and with -- they hope that we have an intact and secure staple line (ph). 694
695
So recently, just doesn't know usability, we get there and evaluation of powered versus 696
manual. And this highlights some discrepancy between the two. We would -- through a 697
system usability scale, that actually favored powered staplers. So the user experience is 698
favorable on the powered versus the manual for these cases. Powered more comfortable 699
and more stable on the end defector (ph) during firing. 700
701
And then we know that there one -- one manual device was significantly lighter than the 702
others tested. So, point being is there can be differences among the models across 703
manufacturers and all that goes into usability. So minimizing discrepancies amongst the 704
staple fleets can help them -- improve that usability and theoretically improve outcomes. 705
706
So in summary, a patient risk can be high, there are certainly certain procedures where 707
that -- that can be an injurious or fatal scenario if something goes wrong. Patient risk we 708
feel is consistent with a Class II definition of moderate risk to a patient. And we need 709
emphasis on usability, what I called that (INAUDIBLE) -- the stapler tissue interface. 710
And that gets more complicated than just a design issue, that's biomechanics, that's 711
physical (ph) elasticity of tissue. So that goes into the special controls potentially 712
through instructions for use in training and labeling. So that's where we think -- and we 713
are headed in that direction. I think we'd -- we should continue to do so. 714
715
OK, that's all I have. Questions? Yes. 716
17
717
LEWIS: Oh, could you explain about realtime, relationships between this work on 718
complications in the manufacturer. Are you all in constant contact? Do you get -- you 719
get report, do you immediately all have a -- like a red phone (ph) to go back and forth 720
between them? Or, you know, how does that work? And do they have access to this lie 721
(ph), I mean, can they -- like every day pick it up and see where you are, what you're 722
looking at about your products? 723
724
LUCAS: OK. Good question. No, it’s not a live relationship with mainly (ph) so, we all 725
-- we do have a strict conflict of interest, first of all, for ECRI Institute to accept any kind 726
of research or monetary funding from manufacturers, because we evaluate medical 727
devices. So that's just – I just want to put that statement for the record. 728
729
But the relationship with adverse events, so what will -- what happens most often is that 730
when we receive reports and we -- and through our problem reporting network, our 731
engineers and clinicians will decide that this is worthy of a publication, that's when we 732
have a correspondence with the manufacturer. So everything that we put out on the 733
hazard and alerts slide that I mentioned, is reviewed by the manufacturers prior to 734
publication. So we have the dialogue at that point. 735
736
LEWIS: Also are the hospitals at all required to communicate with you and 737
(INAUDIBLE) where if something goes wrong with (ph)? 738
739
LUCAS: No, there's no requirement to report to us. The Patient Safety Organization is 740
voluntary reporting, TRN is voluntary reporting, we don't have any regulatory authority 741
to -- into mandate reporting. So we just have to encourage that effort. 742
743
LEWIS: Dr. Lucas, you mentioned the hospital memberships in your organization. Can 744
you elaborate on what that means exactly? 745
746
LUCAS: Sure. We have many products and services that would -- we provide to 747
hospitals and -- and to manufacturers as well on the product side. The -- and 748
memberships can include publications, service can -- services can include consultations 749
or accident investigation. So it's really a wide array of products related to a supply chain, 750
technology safety, patient safety, risk management, legal, et cetera. 751
752
LEWIS: You have -- as I understand, you have no direct connection to the FDA and you 753
have no direct regulatory authority. So, how do you -- when your -- you have obviously 754
very significant findings. How do you actually affect change? What is the -- I simply 755
don't understand exactly how you operate it. If you clarify that. 756
757
LUCAS: Sure. So, our primary interest and mission is to improve patient care and 758
patient safety. So, the fastest way that we do that is through our membership. We touch 759
most of the hospitals in the U.S. So -- when we have an issue through this reporting 760
mechanism, we can publish that directly to everyone without regulatory oversight, 761
18
frankly. So with that independence is advantageous for that. So it gets directly to the 762
users very quickly. 763
764
So -- yeah? 765
766
LEWIS: Wouldn't be fair to say that you function like a medical consumer reports type 767
organization? 768
769
LUCAS: Yeah, the component where we do medical device evaluations where we're 770
doing bench top (ph) testing and comparing products and ranking them on safety and 771
usability, et cetera. That is very synonymous to the consumer ports for consumer 772
products. 773
774
LEWIS: It's my understanding at the current time that some of the manufacturers of 775
staplers basically are having great difficulty meeting supplies and many hospitals actually 776
have been force into techniques of actually rationing the use of staplers, because they're 777
not readily available. And having pre-programmed request for staplers before the day of 778
surgery which has produced some really severe problems in some (ph) busier (ph) 779
hospitals. 780
781
That obviously has tremendous implications for having redundancy and supply and 782
adequate things such as you've advocated for backups. Is the organization aware of this 783
and have you looked into it all at the current time -- my understanding is it’s been going 784
on for a year or two now and is not resolving. 785
786
LUCAS: Well, that's interesting, I'm not aware of that, it's a function of a contributing 787
factor to the investigations that we've done. So not specifically. But that is something 788
that absolutely can affect, especially the remediation or selection of the corporate stapler 789
for use. 790
791
LEWIS: Yeah. And the final question is, in differentiating malfunctions are -- 792
malfunctions of the instrument per se versus faulty use issues. You cited for example 793
closing stapler on a -- on metal clippers something, it prevents its normal inclusion. How 794
do you really differentiate those, since one is entirely a user issue and the other is a 795
device issue? 796
797
LUCAS: It’s a user issue perhaps, however, I mean, we have to think about the surgical 798
field that we're working in and a lot of times it’s tight spaces. So, we feel that sometime -799
- that if we focus on -- for example the geometry of the weight of the stapler or the 800
usability of the stapler itself may reduce those complications. I mean there's no scenario 801
where I've heard that the stapler was intentionally fired on an adjacent instrument. 802
803
So, you know, there is a usability, that's the definition of usability, right? So we feel like 804
more emphasis there will reduce that type of scenario. 805
806
19
LEWIS: Any other questions? Yes sir? 807
808
POSNER: Hi, Philip Posner. You report to hospitals and manufacturers, FDA, you can 809
see information. I wonder if there's any way to let patient organizations and patients get 810
the information. Because if I were a patient going in for any of these procedures, I’d 811
really like to know about the staplers that they're using. 812
813
LUCAS: Fair enough. I mean we have -- there's limited public, like on our website 814
information on specific cases right now. But that's a great question. And we've tend -- 815
we think that when we -- to make change going back to Dr. Lewis' question earlier, a 816
quick way to do that is to impact the hospital so that all procedures are changed 817
accordingly. 818
819
So, you know, in a sense that does change, that helps patient safety but correct, we don't 820
have the -- the database, the database accessible directly public right now. 821
822
POSNER: One suggestion, you know, the new move through (INAUDIBLE) with 823
hospital database is to have patient engagement groups working with hospital boards. 824
And for you to suggest that the hospital share that information with the patient groups 825
they are working with the individual hospital would be very useful. 826
827
LUCAS: Great comment. Thank you. 828
829
LEWIS: Mr. (ph) Meurer? 830
831
MEURER: William Meurer. Could you give some examples of other Class I devices 832
that have made your top 10 lists? 833
834
LUCAS: Frankly, I’ll have to do a little digging for that. Yeah, I don't know off the top 835
of my head. Good question. 836
837
LEWIS: Dr. Levy? 838
839
LEVY: Now with the -- they reported there were 42 alerts in 10 years for the considered 840
device. Is that -- can you comment on the incidents for years if it was rising, was it 841
average for (ph)? Is it falling? And number two, related question, what conditions 842
provoke and alert release (ph)? 843
844
LUCAS: Sure. As far as the incident rate, we've not seen really a fluctuation’s been 845
rather steady over the years. With regard to what qualifies as an alert. If we investigate 846
the problem and consider it a patient safety risk, that can potentially be preventable. 847
That's another factor. Then we'll pub -- that's -- when we'll publish that. So -- but to do 848
that, we want to have recommendations in there, we don't want to just say this is a 849
problem. So, that's where we have, going back to Dr. Hicks' question, that's why we have 850
20
the correspondence between the manufacturer to make sure that those are on point. So, 851
that's how that gets through. 852
853
LEWIS: Yes, Dr. Meurer. 854
855
MEURER: William Meurer. Do you scale it to like how many of the devices are sold 856
annually or provide, I guess, context of at least an estimate knowing that you might sell 857
more than you actually deploy in (ph) patients? But do you have estimates on that in 858
your reports or access to that information? 859
860
LUCAS: Are you referring to a number of uses or market share or? 861
862
MEURER: Yeah, I think that how many times they get fired and nothing bad happens 863
recently … 864
865
LUCAS: Right. 866
867
MEURER: … (INAUDIBLE). 868
869
LUCAS: So, we don't have the actual denominator, you know, but we -- and actually I 870
think the industry presentation, Medtronic folks (ph) have that denominator. So, that's 871
going to be coming. But, yes, I mean conceptually the denominator is massive. So that 872
there not report that we see percentage wise is fairly low. And constant over the years. 873
874
LEWIS: Dr. Hicks. 875
876
HICKS: Yeah, I just want to ask. You know, the FDA had data, you know, that they 877
provided nationally that there were 366 deaths, 9,000 serious injuries and 32,000 878
malfunctions, up through March of last year. Now, we’re over a year -- over a year of 879
and a couple months later to get to this panel. Is there some -- something that causes that 880
kind of a delay or what was the trigger point (ph)? It seems like with those kind of 881
numbers, would have gone off in somebody's head that, look, that's a lot of numbers. 882
883
So, what leads (ph) the trend -- what decides when you get him (ph) a panel like this look 884
at issues? 885
886
LUCAS: Well, that's probably a question directly for the FDA folks. You know, from 887
ECRI Institutes perspectives, it kind of goes back to when we feel that there is a patient 888
safety risk, we publish in. Anyway, we don't have -- and it can be, it doesn't have to be 889
300, I mean it could be a single death. I mean if there's a case that we get that's kind of 890
nuisanced or, you know, centric, even if that's the case, we'll – we’ll want to publish that 891
out. So, as we've done for staplers for really over the years. 892
893
LEWIS: Yes, Dr. Bloom. 894
895
21
BLOOM: Dr. Lucas, the medical legal impact finding of your organization might have 896
on a particular case or a particular class of device must be overwhelming. To what 897
degree does ECRI interact with individual lawsuits or class actions suits? 898
899
LUCAS: Sure. So, we do as part of our investigation services provide expert testimony 900
service as well. So, usually the way that works, as we'll get contracted to do an accident 901
investigation very soon after the incident occurs like that day or next day or whatever. 902
And then if that carries on to suit, we'll stick with the -- whoever we're working for and 903
provide that testimony. 904
905
We do also take a subset of just what we call straight forensic cases or litigation cases. If 906
we determine that there is something to gain from that from a patient safety perspective, 907
we'll take that on as well. But, it's more weighted toward the accident investigation for 908
hospitals. 909
910
LEWIS: Dr. Lucas, thanks very much. We need to move ahead (INAUDIBLE). 911
912
LUCAS: You’re welcome. Thank you, panel, appreciate it. 913
914
LEWIS: Next, we'll hear from industry. And we have two representatives, from the 915
Medtronic Minimally Invasive Therapies Group. Medtronic and its Covidien entities, 916
(INAUDIBLE) operational headquarters in Minneapolis. Dr. John de Csepel is the Chief 917
Medical Officer, Vice President of Global Affairs and Dr. Sam Ajizian is the Vice 918
President of Medical Safety. 919
920
Gentleman, thank you for coming. I might note for the record that -- of the three major 921
manufacturers of stapler as a stapler devices only Medtronic has appearing this morning 922
before the FDA has not heard from the other representatives, who actually make a 923
significant fraction to staplers. Thank you for coming. 924
925
DE CSEPEL: Thank you, Dr. Lewis. And good morning to the panel and to all present. 926
My name is Dr. John de Csepel, I'm the Chief Medical Officer and leader of the Medical 927
Affairs Function for the Minimally Invasive Therapies Group which is one of four 928
business groups at Medtronic. 929
930
In the past, I've been the Chief of Minimally Invasive Surgery at St. Vincents Hospital in 931
New York City. And I remain a practicing trauma surgeon. On behalf of my colleagues, 932
I want to thank the panel and the FDA for the opportunity to present our Internal Surgical 933
Stapling Devices, as well as, the FDA’s proposed path forward. 934
935
To make it easier from here on out, I’ll refer to internal surgical stapling devices as 936
staplers. 937
938
Today, you'll hear a few key points. First Medtronic staplers have a well established 939
safety profile. Second, complaint rates for our staplers have been low and stable. And 940
22
most the complications are related to the underlying surgical procedure, patient 941
comorbidities and the manner in which the device is used. We take a direct approach to 942
patient safety and mitigate stapler related risks through labeling, training, and innovation. 943
944
Third, Medtronic supports reclassifying all internal staplers as the Class II devices, and 945
implementing clinically relevant special controls. 946
947
Further discussion is needed regarding the specifics of the proposed controls, and the 948
extent to which these controls would be relevant to devices whose safety and 949
effectiveness had been established over years of clinical use. 950
951
For today’s presentation, I'll provide an overview of Medtronic staplers then my 952
colleague Dr. Samuel Ajizian will walk you through how we handle complaints and the 953
data on the safety and performance of Medtronic staplers. I'll then conclude our 954
presentation with our thoughts on the FDA's proposed reclassification order and draft 955
labeling guidance. 956
957
Since their introduction in the 1960s, staplers have helped revolutionize surgical practice. 958
Principally by paving the way for minimally invasive and laparoscopic surgery which is 959
demonstrably improved outcomes for patients. 960
961
Staplers decrease the time we spend in the OR and with their consistent mechanism of 962
action, decease surgeon variability as compared to suturing by hand. The use of surgical 963
staplers' standard practice in a variety of surgical procedures and are used in millions of 964
surgeries each year. 965
966
I developed a renewed appreciation for the value of staplers when I started undertaking 967
yearly missions for the aid organization Doctors With Borders. Over an eight-year 968
period, I worked in war zones in Africa and the Middle East. We didn't have staplers and 969
had to hand sew everything. The delay caused by hand suturing frequently left critically 970
injured patient needlessly waiting for treatment. 971
972
Medtronic and its legacy companies, U.S. Surgical Corporation and Covidien have been 973
the forefront of innovation in surgical stapling. The first open stapler was introduced in 974
the US in 1967, and the first laparoscopic one in the early 1990s. And just recently, the 975
first powered stapler has come to market. 976
977
Today Medtronic markets 23 surgical staplers with a range of staple lengths that are 978
designed for different tissue types and thicknesses. Consistent with the FDA's 979
reclassification proposal, all of our current staplers have been submitted for clearance as 980
Class II devices. 981
982
Medtronic conducts extensive testing on our staplers. Our current pre-clearance protocol 983
includes testing for stability, sterility, biocompatibility, safety and performance in vitro, 984
23
in vivo and ex vivo as well as usability. This includes evaluation of stapler formation, 985
firing force, hemostasis and staple line strength. 986
987
In addition, we conduct the usability testing, validating our instructions for use and 988
evaluating device performance against its design specifications. For our powered 989
staplers, Medtronic conducts additional pre-clearance testing. All devices are evaluated 990
for electrical safety consistent with international testing standards and all software 991
undergoes verification and validation testing. 992
993
Staplers that are reusable are tested for repeated sterilization and reliability with repeat 994
use. And the majority of surgeries, there are no complications. Nonetheless, when I 995
consent my patient before taking them to the OR, I discussed the risk inherent to the 996
procedure. The frequency risks are often influence by such things of the patient's age and 997
their comorbidities. 998
999
For example when performing erectile (ph) resection for cancer, an anastomosis is 1000
formed to reconnect the bowel. It's up to a 10 to 15 percent risk of anastomosis leak 1001
which can be increasing the patient who is diabetic or has received prior radiation 1002
therapy. 1003
1004
Medtronic helps mitigate potential risks associated with the use of our staplers through 1005
product labeling, training and device innovation. All these are intended to help ensure 1006
that surgeon correctly and safely use our staplers. 1007
1008
Product labeling includes detailed information on appropriate stapler use and staple size 1009
selection as well as relevant contra (ph) indications, warnings and precautions. We 1010
provide training and educational resources to surgeons and their staff including lectures, 1011
surgical stimulations, and case observations. We support fellowship programs and 1012
medical society training programs. 1013
1014
We also continue to innovate to make stapling easier and more consistent. An example 1015
of this innovation is our Signia Stapling System, a powered stapler which adapts stapling 1016
speed to tissue thickness, slowdown when encountering thick tissue to help the surgeon to 1017
achieve a consistent and effective staple line. 1018
1019
With that now, I'll turn the microphone over to my colleague Dr. Sam Ajizian to review 1020
the safety and performance to Medtronic staplers. 1021
1022
AJIZIAN: Thank you, John. My name is Samuel Ajizian and I'm pediatric intensivist 1023
and the Vice President overseeing medical safety with the minimally invasive therapies 1024
groups (ph) at Medtronic. 1025
1026
In the next few slides, I'll present an overview of our process for insuring device safety 1027
and provide a detailed look at compliant data for our surgical staplers. Let me begin with 1028
an overview of how we handle complaints. Medtronic monitors the performance and 1029
24
safety of our staplers through a robust quality system. This includes advanced design and 1030
manufacturing controls in a comprehensive Post-Market Vigilance Program. Our Post-1031
Market Vigilance group includes doctors, nurses, engineers and other trained personnel. 1032
This recollects, evaluates, investigates and reports customer complaints to the FDA in 1033
accordance with the agency's guidelines. 1034
1035
In order to understand our compliant handing process, it's important to start by explaining 1036
what a complaint is and what a complaint is not. FDA defines a complaint as any 1037
written, electronic, or oral communication that alleges device deficiencies related to the 1038
identity, quality, durability, reliability, safety effectiveness or performance of a device 1039
after it is released to a distribution. 1040
1041
Simply put a complaint is any information received by Medtronic or by the FDA that 1042
suggest a problem may have occurred before, during or after use of a device. A 1043
complaint does not necessary mean a stapler malfunctioned or caused injury to a patient. 1044
1045
Complaints regarding Medtronic device is come from a variety of sources and vary 1046
widely in terms of their substance and the amount of information that is provided or 1047
available. They can involved relatively minor issues such as the packaging was damaged 1048
prior to delivery or raise more serious concerns such as the patients was injured. 1049
1050
For staplers, the vast majority of complaints we received do not relate to a patient injury. 1051
And finally, without context, the number of reported complaints does not provide reliable 1052
information regarding a device’s relative performance or safety absent a denominator. 1053
For example, how often the device is used in clinical practice. It is impossible to asset 1054
the rate at which a reporting event occurs in clinical practice without a denominator. 1055
1056
All complaints are thoroughly investigated by Medtronic Post-Market Vigilance team in 1057
consultation with appropriate subject matter experts in design quality manufacturing and 1058
medical safety. 1059
1060
The investigation includes collection and analysis of available information regarding the 1061
reported issue, review of the products manufacturing history and review of the product’s 1062
complaint history and other relevant data. And when available, testing on the actual 1063
device involved. 1064
1065
The ultimate goal is to determine the root cost of the alleged problem to identify any 1066
potential safety or performance issues and when appropriate, to implement corrective 1067
action. 1068
1069
In most cases where we have sufficient information to make an assessment, the root 1070
cause of the complaint is found to be related to the inherent risks of the surgical 1071
procedure, patient condition and comorbidities or the manner in which the device was 1072
used. 1073
1074
25
A parallel investigation is conducted the medical safety team for all complaints involving 1075
a reported death or serious injury to a patient. Our medical safety team of doctors and 1076
nurses conducts interviews with clinical personnel, reviews medical history and provides 1077
an independent assessment of the complaint. 1078
1079
In performing both assessments, we take a conservative approach and apply very low 1080
thresholds to ensure that all reportable complaints are submitted to the FDA. 1081
1082
Medtronic has always provided information to the FDA on reportable complaints 1083
involving malfunction, death and serious injury consistent with the agency's guidelines. 1084
1085
Traditionally reportable complaints have been submitted to the DFA in the form of 1086
individual Medical Device Reports or MDRs, which the FDA incorporates into its 1087
MAUDE database. 1088
1089
In 1997, the FDA introduced an Alternative Summary Reporting or ASR pathway for 1090
certain medical device complaints. Between 2001 and 2017, Medtronic submitted 1091
reportable complaints involving malfunctions to the FDA on a quarterly basis through the 1092
ASR pathway. Throughout this time Medtronic submitted reportable complaints 1093
involving death or serious injury as individual MDRs rather than through the ASR 1094
pathway. 1095
1096
In 2017, in conjunction with the transition from legacy Covidien to Medtronic complaint 1097
handling software, we stopped using ASRs for stapling products and resumed submitting 1098
individual MDRs for all reportable malfunction complaints. 1099
1100
Medtronic often submits multiple MDRs regarding a single patient compliant involving 1101
our staplers. For example, two MDR reports maybe submitted for a single complaint 1102
where the device includes both the stapler handle and the stapler reload. This is 1103
consistent with FDA guidance but it results in numerous duplicate reports in FDA's 1104
MAUDE Database. 1105
1106
Over the last two years, Medtronic submitted roughly two MDRs to the FDA for each 1107
reportable complaint it received. Medtronic staplers are used in more than a million 1108
surgical procedures each year. These procedures vary widely in terms of the operation, 1109
patient condition and comorbidities, the experience level of the surgeon and operating 1110
room staff and the surgical facilities. 1111
1112
Many of the procedures in which staplers are used are technically difficult and often are 1113
performed on high risk patients. Despite this, complications with Medtronic staplers are 1114
rare. 1115
1116
These next few slides will focus on complaint data. There has been considerably 1117
attention recently to the absolutely number of complaints involving staplers that had been 1118
reported to the FDA. In order to put these absolute numbers in context, we will apply a 1119
26
denominator and illustrate rates for these complaints. This figure reflects all reportable 1120
complaints received by Medtronic in the period from January 1, 2011 to March 31, 2019. 1121
1122
On this slide and subsequent slides, the left y-axis is the total number of reportable 1123
complaints per year as shown in the bars and on the right y-axis is the rate of these 1124
reportable complaints per year as shown in the green line. 1125
1126
The darker blue represents complaints reporting malfunctions, the light blue are those 1127
reporting serious injury and the purple which is not visible because there are so few are 1128
those reporting patient death. As you can see, complaint rates have been low and have 1129
remained stable throughout this period ranging from 0.06 percent to 0.10 percent. It is 1130
important to emphasize again that these rates are based on all reportable complaints 1131
received by Medtronic regardless of whether any relationship to the device exist. 1132
1133
This next figure focuses specifically on complaints involving the death of the patient who 1134
had a surgical produce during which a Medtronic stapler was used. Again, these are all 1135
such complaints received by Medtronic and not confirmed device related events. 1136
1137
Complaint rates have been low and stable throughout this period averaging less than 1138
0.0005 percent. By comparison, the mortality rate in the general population of patients 1139
undergoing surgery in the United States is estimated to be between 0.2 percent and 2 1140
percent. 1141
1142
This figure focuses specifically on complaints involving a serious injury related to a 1143
surgical procedure during which a Medtronic stapler was used. These complaints have 1144
involved a wide range of alleged issues, including use of an intraoperative X-ray and 1145
prolonged operative time. Both reportable -- considered reportable patient harms (ph). 1146
1147
Again, these are all such complaints received by Medtronic and not confirmed device-1148
related events. As you can see complaint rates have decreased during this period from 1149
0.008 percent to 0.017 percent. By comparison, the reported incidence of complications 1150
in general surgical practice is estimated to range between five and 15 percent. 1151
1152
This figure focuses on complaints alleging a reportable device malfunction. The 1153
complaint rate was low, ranging between 0.05 percent and 0.09 percent. None of these 1154
malfunction reports involved a death or injury to a patient. So to summarize, accounting 1155
for both MDR and ASR reporting, the analysis of our complaint data did not identify any 1156
new safety signals across our stapler portfolio. 1157
1158
Complaint rates for our staplers are low and have remained so over the last seven years. 1159
Complaints involving death and serious injury are rare and in the case of serious injury 1160
have decreased by nearly 50 percent. Most of these complaints again relate to the 1161
inherent risk of the surgical procedure, patient condition, comorbidities, operative 1162
experience, and the manner in which the device is used. 1163
1164
27
I will turn the presentation back to Dr. de Csepe who will cover Medtronic physician on 1165
the FDA's draft reclassification order and proposed labeling guidance. 1166
1167
DE CSEPE: Thank you Dr. Ajizian. I'd like to share with you, our view of the FDA's 1168
proposed reclassification order and draft labeling guidance. Medtronic supports the 1169
FDA's proposal to reclassify all internal staplers as Class II devices. 1170
1171
A regulatory approach that's consistent with our own practice. Reclassification will help 1172
ensure that all staplers comply with the same standards. Medtronic also supports the 1173
FDA's efforts to standardize control for all staplers. Further discussion is needed 1174
regarding the specifics of the FDA's proposals and the relevance of the proposed special 1175
controls to devices that have been in clinical use for years. 1176
1177
The FDA's list of proposed preclearance testing generally appears to be consistent with 1178
our current testing practices. The list is relatively high level and additional discussion is 1179
needed to fully evaluate the proposal. For example, we don't believe that testing controls 1180
should be retroactively applies to devices that have a strong safety profile established 1181
over years of clinical use. 1182
1183
Medtronic would like to work with the FDA and other manufacturers to develop special 1184
controls that are clinically relevant and help enhance the safety use of these devices. We 1185
believe that testing for powered staplers should be specifically addressed in the controls. 1186
1187
Medtronic plans to submit further commits on the proposed controls by the June 24 1188
deadline and hopes to discuss the details of the proposal with the FDA. 1189
1190
Our product labeling contains accurate and appropriate information regarding the safe use 1191
of our staplers. We support the FDA's proposal to update internal stapler labeling to 1192
further increase physician awareness and enhance the safe use of these important devices. 1193
1194
Medtronic would like to work with the FDA and other stakeholders to develop a 1195
consistent framework for internal stapler labeling, with the focus on the information as 1196
clinically relevant and helpful to surgeons. In particular, we want to be careful that the 1197
information contained in the labeling does not interfere with clinical decision making. 1198
1199
In conclusion, I'd like to walk through our answers to the FDA's questions submitted to 1200
this panel. As to question one, we generally agree that the FDA's questions reflect the 1201
most common risks associated with the use of internal staplers. The one exception to that 1202
is local cancer recurrence. This is generally a function of achieving clean margins at the 1203
time of surgery. It's also important to emphasize that many of the risks listed in question 1204
one are associated with the surgical procedure, comorbidities of the patient or the manner 1205
in which the device is used. 1206
1207
As to question two, the available data provides strong evidence of clinical safety and 1208
effectiveness of our staplers. As to question three, the FDA's list of proposed special 1209
28
controls is a productive starting point. Questions remain as to the specifics of these 1210
proposals and how they’d be (ph) applied to devices that have been clinically used for 1211
years. 1212
1213
Further, we respectfully request a recommendation from the panel that the FDA work 1214
interactively with manufacturers and other stakeholders on future special controls. As to 1215
question four, we agree that the special controls should be required for internal staplers. 1216
We do not believe that our staplers present an unreasonable risk of injury. As to question 1217
five, consistent with our own practice, we agree that internal staplers should be treated as 1218
Class II devices. 1219
1220
Thank you for your time and this opportunity to present. Dr. Ajizian and I would be 1221
happy to answer any questions that you may have. 1222
1223
LEWIS: Thank you, I'd like to lead off with some questions. Actually the first is that in 1224
the labeling of instructions for users, it seems to me there's inherent conflict between 1225
legal advice that the company has get which is to list every possible complications and be 1226
sure that covered versus readability and intelligibility for the user who would, faced with 1227
a multi-page document, often doesn't read at all. How do you resolve that in terms of 1228
having the essential things there and trying to ensure that they're actually read by the 1229
users? 1230
1231
AJIZIAN: I'd be happy to take that. We make every effort to have meaningful 1232
instructions for use that are clinically resonant and help users. As clinicians ourselves, 1233
we know that's not characteristic of every IFU we've ever read. We continually work to 1234
ensure that first and foremost, the IFUs give the proper instructions while meeting all the 1235
regulatory guidelines for that device class but we constantly look at usability, human 1236
factors and evaluate for many devices the efficacy, if you will, of those instructions. That 1237
is not true for most Class I devices, but certainly for devices like this, that is something 1238
we're always trying to improve. 1239
1240
DE CSEPEL: And perhaps I can add to that. Labeling is the starting point but also an 1241
important component is training, something that we put a lot of vigor into training 1242
surgeons and it starts with training programs that we sponsor in surgical residency, 1243
extending to fellowship. It also includes sponsoring society trainings. We work with 1244
highly experienced surgeons, those who've had decades of experience to put them in 1245
positions where they can train other surgeons who are newer in practice, how to use the 1246
devices in a safe manner. 1247
1248
LEWIS: Since one of the major use issues is inappropriate staple length relevant to tissue 1249
thickness or inappropriate stapler use just beginning (ph) for tissue thickness, are there 1250
any automatic staplers that compensate for tissue thickness in the application of the 1251
stapler and the Advil basic renerve (ph) that simply automatically adjust to the tissue 1252
thickness so that's not a requirement? 1253
1254
29
DE CSEPEL: First off, we have a variety of reloads to which the difference between one 1255
(INAUDIBLE) is the staple length and we want to provide options to surgeons to choose 1256
which might be the appropriate stapling for the tissue that they’re going to be stapling 1257
across. Those are available for both non-powered and powered staplers. Powered 1258
staplers also, our Signia system that I mentioned earlier, also has a feature called force 1259
feedback and when it encounters particular thicker or dense tissue, the staple firing slows 1260
down to allowed additional compression of the tissue. We've heard from surgeons that 1261
they really like these types of features. 1262
1263
LEWIS: OK, are there any differences in the sterility procedures for powered versus 1264
manual staplers? In other words, do you use chemical sterilization versus heat 1265
sterilization or is that an issue at all in terms of the usage of the devices? 1266
1267
AJIZIAN: Yeah, we take sterilization extremely seriously across our product portfolio 1268
including other devices. It's a key and central element of our preclinical testing. We also 1269
continually evaluate in that testing, the cleanliness and sterility of devices after repeated 1270
cycling, their lifespan of course and a device does not go to market without meeting 1271
international standards for sterility testing. 1272
1273
LEWIS: With the powered staplers, are all the elements that are used to sterile or do they 1274
have to go with a protective cover of some kind (ph)? 1275
1276
DE CSEPEL: All right, different elements are reused, (INAUDIBLE) before, a non-1277
powered stapler traditionally is a single use instrument and disposed of. So the sterility 1278
issue is one particular concern to us when you have a device that can be reused. So in a 1279
powered stapler, for example, the reload, the stapler cartridge is disposable but the shaft 1280
between the powered handles is a reusable component. 1281
1282
There's a clam shell that covers the handle, the power pack itself, that's the single use for 1283
disposable item but the power handle then is reuse. And so there are methods that we 1284
described and teach too (ph) of taking this non-sterile powered handler or powered pack, 1285
putting it into the sterile clam shell. So there's elements of both and we focus a great deal 1286
on the sterility of the parts that are reused. 1287
1288
LEWIS: But would it be correct to say that the FDA has no way of testing the reusable 1289
elements since they're not going to be present in actual use in any hospital when that 1290
happens? 1291
1292
AJIZIAN: Dr. Lewis, I have the trouble trying to describe the FDA's capabilities for 1293
testing. I just don't know those. 1294
1295
LEWIS: Dr. Kraus? 1296
1297
30
KRAUS: So we do have a science and engineering labs and if we had a question about 1298
testing that type of equipment we could ask them but as far as I know that hasn't been 1299
done and we don't do it routinely. 1300
1301
LEWIS: Yeah, that would seem to be a potential sterility issue because it does involve 1302
the possibility of contamination that would fall outside of your general purview. 1303
1304
KRAUS: Right, so I think that's part of the issue with staplers is that the reusable 1305
component, we don't see that, we don't really get to review that because those devices 1306
aren't Class I exempt. If there was a submission on reprocessing then that would go to 1307
our reprocessing group, they would look at all the data. 1308
1309
I'm not aware of a product code for reprocessed staplers, there may be one, I don't know 1310
that we've seen any so, you know, that's something we have to look into but certainly 1311
with the up classification we would get all that information and we would make sure that 1312
the reprocessing actually provided a sterile device, clean and sterile and that all the issues 1313
identified in our reprocessing guidance are addressed. 1314
1315
LEWIS: Thank you. Questions from the panel? 1316
1317
HICKS: Hicks. There's been a lot of data, you know, that you've been able to reveal so 1318
in any case, great concerns over labeling. Labeling to every page, labeling (ph). And my 1319
concern is, it's just labeling doesn't always get the job done. The user of this equipment, 1320
how do you look at the best way -- if you could, you know, have a magic pill, how would 1321
you do it to get people prepared to use the instrumentation in a safe way. 1322
1323
Because I can tell you, if you look at the basic information on some of the labeling, it 1324
looks like the book you get on your new car, you just throw it in the glove box because 1325
it’s just too much information, so what's the key to getting from manufacturer to the user 1326
to do it in a safe effective way? 1327
1328
DE CSEPEL: Yup. I think the training on the safe use of staplers occur at many time 1329
points in the course of the surgeon's career. So I think that starting critically in surgical 1330
residency training, appreciating differences in tissues, difference in patient condition and 1331
also the safe application with stapler is the critical first step and to the extent that we can, 1332
we support programs to make sure that that training is optimized. Speaking about for 1333
example, the different stapler lengths that are available to a surgeon to use. 1334
1335
And then that continues in through fellowship training we sponsor minimally invasive 1336
surgery fellowships nationwide and then importantly as a surgeon's practice, continue 1337
touches with the surgeon our account representatives are constantly present for surgeons 1338
as a resource to answer questions. But we also proactively reach out, we speak with 1339
surgeons, our customers and our users on a regular basis to understand if there might be 1340
any opportunities for training and then we take those opportunities. 1341
1342
31
Does that (INAUDIBLE). 1343
1344
AJIZIAN: Dr. Hicks, can I just add to that? 1345
1346
HICKS: Yeah, sure. 1347
1348
AJIZIAN: I think the high level answer is that labeling alone, regardless of what our 1349
dream state (ph) is, is not going to solve all the problems that are user related for really 1350
many devices, including staplers. And our philosophy is to look at the triad of labeling, 1351
of cleaning and of innovation and combine those into an experience for the surgeons that 1352
varies in (ph) attention from the time you start using a device the first day where there 1353
may be many, many representatives supporting your ORs until you've adopted on that 1354
learning curve to frequent reconciliation as needed, to the special training programs that 1355
Dr. de Csepel alluded to. So it really has to be a combination of those things. We don't 1356
see labeling alone or quite frankly any of those three alone as sufficient and must be in 1357
combination in working with our partners. 1358
1359
LEWIS: Dr. Miller? 1360
1361
MILLER: Yes, Mike Miller here, first of all let me congratulate you. I'm impressed with 1362
your thoroughness and your clear thinking and your approach to creating the devices and 1363
tracking you performance and I'm very happy to see that. 1364
1365
I have some questions for Dr. Ajizian. How confident are you that the data you showed 1366
us is complete and really capturing all the problems that occur and complaints that might 1367
be out there that, you know, somebody just may have and then (INAUDIBLE) other one 1368
staple again or? 1369
1370
AJIZIAN: Certainly, I think the theme is there, what do we think of underreporting of 1371
complaints and certainly that's a well known aspect of complaint-driven databases, 1372
complaints are under reported, we know it, everyone here at FDA knows it and all of you 1373
know it. 1374
1375
We do however take great measures to try to acquire as many safety signals as we can, 1376
both through critical relationship with our surgeons directly in many cases, our key 1377
opinion leaders, our representatives in the field who observe many cases and by law are 1378
bound to report these things to us within 48 hours. 1379
1380
We also scour the literature continuously, the large literature of your team (ph) that looks 1381
for our devices in association with complications, malfunctions, serious injuries or death 1382
in the literature, and work with other partners including ECRI at times, that Scott 1383
mentioned earlier, to look for signals in every place possible. And then taking 1384
opportunities like this to educate our peers and the importance of speaking to us during 1385
the eventuality, though rare, the device does malfunction. 1386
1387
32
MILLER: And also if I may, you mentioned a couple of times that you sort of already 1388
treat the devices like Class II devices and you developed your own special controls and in 1389
some ways. What kind of change would you expect to see in your business, should the 1390
FDA change the classification to a Class II device? Would you see changes in cost or 1391
R&D process or what kind of effect do you think this will have on you if the FDA makes 1392
a decision to change to a Class II device? 1393
1394
AJIZIAN: As we said Dr. Miller, we already treat these devices as Class II. They've 1395
been 510(k) submitted and Dr. Kraus would be happy to know that we've done and 1396
validated all of our sterility testing and cleaning and presented this if it's a Class II device. 1397
1398
The impact on our business, I think varies, it's impossible to say depending on what the 1399
nature of the controls are and know that we are aligned with FDA, that these devices 1400
should be treated as Class II, but we do on further that conversation with respect to, as 1401
Dr. de Csepel said earlier, perhaps some older stapler lines that have a demonstrable 1402
amount of clinical performance and safety. So I think more to come but we look forward 1403
to dialogue with FDA and our partners to help shape those controls in a meaningful way 1404
that contributes to safety. Thank you. 1405
1406
LEWIS: Dr. Pories. 1407
1408
PORIES: Thank you. I also appreciate your presentation and your care, really 1409
extraordinary. But as an educator I find that a bunch of people don't like to be educated. 1410
So, what’s your percentage of that -- of surgeons who actually -- and nurses who actually 1411
take the courses and the ones that frustrate you because they (ph) don't? 1412
1413
DE CSEPEL: As I mentioned earlier courses for those who are currently in practice are 1414
just one component. So, to answer your question, I couldn't give you a percent of those 1415
who have gone through a Medtronic sponsor course or a course of others in the stapler 1416
manufacturing industry. 1417
1418
What I can say is that, I think, that you need to interact and touch these surgeons 1419
throughout the course of their training and I think that can lead to better appreciation of 1420
stapling and safe use of the staplers. 1421
1422
PORIES: How successful are you at that (ph), or how frustrated are you because I'm sure 1423
you want to educate a hundred percent. 1424
1425
DE CSEPEL: Yeah. For those surgeons that we have the privilege to educate, I feel like 1426
we're quite successful. And principally the reason is because we work closely with the 1427
most experienced surgeons. And supply them with the information that they in turn can 1428
make their own. And teach from their own experience as well the specification data that 1429
we may supply to run courses where they can describe the use of a stapler. 1430
1431
33
And also describe the use, the proper and safe use of stapler in the context of teaching a 1432
procedure such as a minimally invasive or Laparoscopic colon resection for example. 1433
And when we do that, we find that we get very good feedback from the trainees, 1434
pharmaceutical attending trainees that go through the course. 1435
1436
LEWIS: Dr. Meurer. 1437
1438
MEURER: Meurer. If a surgeon or a hospital reported a malfunction on the device, do 1439
they get a refund? 1440
1441
AJIZIAN: That's a good question. The policy is in a sense yes, but it's not a 100 percent 1442
guarantee. So there's an -- it depends and neither of us are privy (ph) to really what 1443
governs that. But yes it may happen. 1444
1445
DE CSEPEL: And maybe a way to incentivize reporting. 1446
1447
LEWIS: Philip Posner. 1448
1449
POSNER: Yes, Philip Posner. I think about the teaching, you say want to do and teach 1450
one and that's pretty much what you're saying to do. You're basically going through 1451
Class II procedures and I wonder what the industry standard is since you're the only 1452
industry member that's presenting. And your data is really impressive as to -- and for this 1453
incidence and I wonder of your Class II procedures what you would add to it to make it 1454
even better or what you think you're doing is more than as needed. 1455
1456
So again, we're going to put together some process. And the third questions pretty much 1457
to the FDA is, does the FDA have an ability to oversee the training procedures to make 1458
sure they're adequate. I know with our catheter procedures and hip (ph) procedures and 1459
things like that, it goes to another level because those are really important too, so those 1460
are my three questions. 1461
1462
AJIZIAN: Could you give met the first question again? I'm sorry. 1463
1464
POSNER: Standard in the industry. 1465
1466
AJIZIAN: Yeah, so … 1467
1468
POSNER: So what are the other folks doing? Because again marketing wise you do a all 1469
this … 1470
1471
AJIZIAN: Yeah. 1472
1473
POSNER: …I’d buy your equipment. 1474
1475
34
AJIZIAN: Thank you. And maybe John can, I can't speak to what -- how other 1476
companies are bringing their devices to market and what that regulatory pathway is with 1477
our FDA colleagues. We've shared ours but I don't know that. 1478
1479
POSNER: And then the second one is, of all the procedures you're doing, is there 1480
anything else that you wish you would be doing that would make your numbers even 1481
better or anything that you're doing that you think is really redundant and doesn't need to 1482
be done? 1483
1484
DE CSEPEL: You had commented, then Dr. Posner about very low rates of adverse 1485
events, and we would agree with that. But at the same time we're always looking for an 1486
opportunity to improve the safety if there's anything that we can do to promote that 1487
within the surgical community. 1488
1489
So we're always -- we feel that our labeling currently is meaningful but we're always 1490
happy to engage with the FDA to discuss if there's some way to optimize that labeling to 1491
enhance for use by surgeons, then we're happy to do that. And then we're always happy 1492
to also discuss what we're doing currently in training and if there's ideas about how we 1493
can do it better from the FDA, then we're happy to engage in that discussion. And in the 1494
background of all of this, we're always looking to innovate to make the devices easier to 1495
use even in the most complex of procedures. 1496
1497
POSNER: Thanks. 1498
1499
LEWIS: It looks like there no further questions, so thank you both for excellent 1500
presentation. 1501
1502
DE CSEPEL: Thank you. 1503
1504
AJIZIAN: Thank you. 1505
1506
LEWIS: We'll now hear a series of presentations from the FDA relating to stapler 1507
history, medical device reporting, testing methods and proposed risks, mitigations, and 1508
special controls. Dr. George Gibeily will present on the history and clinical safety 1509
aspects of surgical stapler and special controls and will present on behalf of the FDA. Dr. 1510
Gibeily. 1511
1512
UNKNOWN: So before George starts his presentation, I'd like to answer the part of the 1513
question that was for FDA. For PMA products, FDA does have a great deal of input into 1514
training. For Class I products, we have zero input for training. For Class II products, we 1515
may have some because we can look at the usability studies and what a company does to 1516
show that a surgeon or practitioner can use the device. So we have, you know, some 1517
control. But certainly over PMA products, we can influence the training quite a bit. 1518
1519
35
And I wanted to clarify one thing I said earlier, if somebody has a stapler and it's a single 1520
use stapler but a hospital or the company or somebody else wants to reprocess that single 1521
use stapler, they would get the product code NLL (ph) and that would be a Class II 1522
device, OK. So a single use device that's reprocessed for -- to be used, again we've had a 1523
few of those cleared and they have to go through a whole long process to show that they 1524
can do the reprocessing procedure and at labeling requirements, for example can you do 1525
it 10 times, can you do it once, can you do it twice and data are collected that the 1526
company has to provide to the FDA showing they can actually meet that to reprocess the 1527
stapler. 1528
1529
In the case that you had a device that is sterile but it is intended for reuse, in other words 1530
if you have a stapler that is intended to be re-sterilized because it's not disposable, that's 1531
stapler, we would not look at data because it's a Class I device, we would not look at data 1532
to see that that is on the re-sterilization because that's part of the Class I understanding of 1533
that device. In other words, it's designed for reuse. So there's difference between 1534
sterilizing a reusable device and reprocessing a non -- a device that was not designed for 1535
reuse. So I think just to clarify that. 1536
1537
So, if Medtronic has a stapler and it's submitted to us, and if they want it to say in their 1538
labeling, well you can re-sterilize this 20 times, well, we would look at that, OK. But if 1539
they don't say anything about it, we probably wouldn't look at it because the stapler itself 1540
is considered Class I exempt. 1541
1542
GIBEILY: OK. Dr. Lewis, panel members and guests, my name is George Gibeily. I'm 1543
an FDA Medical Officer with the Center for Devices and Radiological Health. I'm also a 1544
general surgeon, 35 years I've used staplers all my life. I have to say it's a real honor to 1545
be part of this group to improve the safety of surgical staplers. 1546
1547
So, in this presentation, I hope to discuss the evolution of stapler technology to where we 1548
are today, the benefits of stapler technology versus surgeon use. Some of the devastating 1549
complications we see with failure of tissue division and approximation, and ending with 1550
the review of the literature on weakness stapler malfunctions. 1551
1552
The staple has been changing composition for every 50 years, it's those medical grade 1553
famous steel or titanium. In this open forum, it consists of a crown and two limbs, which 1554
have variable heights. The only exemption is destapled which is designed about six years 1555
ago to be applied through an internal stapler through a smaller diameter trocar instead of 1556
the usual 12 millimeter trocar. 1557
1558
The stapler design, however, has changed greatly in the last 50 years and it's the stapler 1559
that impacts the safety of the staple since the staple converts the open staple into speed 1560
(ph) configuration for approximation of tissue, as well from allowing perfusion through 1561
the openings. And so to lose the tissue -- approximately tissues are permeable to blood, 1562
air, bowel content, and other physiologic fluids too tight and the crown can share wire 1563
36
through the entire thickness of the bowel or cause serious (ph) injuries, cell membrane 1564
damage, ischemia and ultimately leak anastomosis. 1565
1566
So ironically, low staples are Class II devices. Staples are currently Class I exempt 1567
devices regulated of what we call general controls, much like a tooth brush. These 1568
controls are much less comprehensive than the special controls used to regulate the 1569
staple. 1570
1571
As Class I devices, surgical staplers for internal use are exempt from 510(k) review. 1572
However, they do frequently become bundled with stapler in 510(k's) admission as our 1573
Medtronic folks have mentioned. And we review these admissions in context of the 1574
staple. But because the staples are Class I FDA designed review than in 510(k) process 1575
and if modification to the stapler occurs in the marketplace sometimes in response to 1576
adverse events, we don't hear about it. 1577
1578
And so, you know, prior to 1990, we have rudimentary types of staplers, the GIA or the 1579
linear stapler cutter, the TA, transverse approximator, and then prior to that -- and then 1580
the circular stapler, of course. And they were used in open surgery and the surgeon can 1581
approach the surgical field in many plains, in many different angles, in a wide open three-1582
dimensional space. And the jobs of the staplers, it could expand to accommodate tissues 1583
of all kinds of sizes. 1584
1585
And then by 1990 with the advent of minimal invasive surgery, there were some very 1586
dramatic changes with regard to staple. One, it had a longer shaft so that it could reach 1587
the surgical site separated from the surgeon by the chest wall or abdomen. The staplers 1588
have to be introduced in the trocar which limited the angle of approach to the surgical 1589
field. 1590
1591
And so the jaws were made to articulate right and left and the jaws are hinge and they 1592
could only open about 12 degrees. And so all of a sudden, the mobility of the tissue 1593
being stapled played a large part in the use of the stapling application. And the surgeons 1594
had to physically load the tissue into the stapler jaws creating the potential protraction 1595
(ph) injuries and tissue tearing. 1596
1597
In addition, access could be increased by decreasing the shaft diameter of the stapler, i.e., 1598
the stapler (ph) I mentioned earlier, to access the operative site through the more 1599
numerous smaller ports, to facilitate approach to the surgical site without loss of exposure 1600
through instrument exchange or scope relocation. 1601
1602
So the determinants of staple line quality and strength, just get back to a little bit of basic 1603
science, aside from the number of rows of staples and number of staples per row, it seems 1604
that the shorter height of the close staple without compromising perfusion, the stronger 1605
the anastomosis, the less likely to leak, it's less likely to bleed or to stenose. 1606
1607
37
And this isn't only determined by pre-fire compression pressure but also by pre-fire 1608
compression time. You can't just get the staple jaws to the firing zone and fire. You 1609
want to wait a little bit so as to get the extracellular fluid added there and get a more 1610
stable uniform tissue thickness and tissue gap setting (ph) in the stapler jaws. 1611
1612
Recognizing that there are changes in thickness in the same -- of tissue thickness in the 1613
same organ, there's differences in solid, liquid and gas components of the organ. Tissue 1614
type, tissue compressibility, pathologic changes, all play a role in determining the ideal 1615
pre-fire compression time and pressure. The more solid component within the tissue, the 1616
greater pre-fire compression you can use without compromising the integrity of the cell 1617
membrane, and recognizing that point is important. And hopefully we can develop, you 1618
know, performance studies to look at that in the future. 1619
1620
So right now, we've got staples that are color coded. The white staple for example has an 1621
open height of 2.5 millimeters, closed to 1.0, is ideal for vascular tissue. The blue staple 1622
is the one I always use in my career. For bowel, it has an open height of 3.5 down to 1.5 1623
closed height is ideal for bowel and then the green for the thicker bowel or stomach with 1624
an open height of 4 and down to 2.0. 1625
1626
So this presumes -- when a surgeon sees this, it presumes that the surgeon knows, with 1627
accuracy, the thickness of the tissues he's going to apply the stapler to. And, you know, 1628
that's not always consistent and I think it's even more difficult than the laparoscopic 1629
environment. Sometimes you really know where the thickness is because you can feel 1630
the tissue and so that does become an issue. 1631
1632
And so income powered staplers with their batteries and motors and software, and I think 1633
potentially it's a real advantage because it decreases the human variable in getting that 1634
tissue gap and having a more uniform staple line. It eliminates the problem of grip 1635
strength. It's no longer an issue for surgeons with glove sizes less than six operative 1636
state, these powered staplers because, you know, it happens automatically. It's a little 1637
heavier than the manual stapler but it allows these surgeons to use it. 1638
1639
It minimizes steep movement. It stabilizes tissues. It standardizes a gap setting of the 1640
jaws of the staple to achieve a uniform and appropriate tissue thickness prior to firing. It 1641
also has software that helps determine the compression -- the pre-fire compression force 1642
and pressure and separates the cutting and stapling phases from that to allow for a more 1643
uniform staple. And so there are a lot of real advantages, I think, to some of these 1644
powered staplers. 1645
1646
The technology is fascinating but it is complex, and with complexity comes lots of after 1647
feedback, comes new paths malfunction, multiple error messages, which requires the 1648
surgeon to understand them in a tough situations sometimes to enable to seamlessly 1649
employ countermeasures. And so there was an active survey of surgeons in 2017 and in 1650
this survey surgeons were asked what do you think causes the failed in staple line? Well, 1651
38
10 percent said it was due to stapler malfunction. And believe it or not, 90 percent said it 1652
was due to poor surgical judgment. 1653
1654
They are choosing the wrong size of staple for the tissue thickness. They're using the 1655
stapler on the damage nerve (ph) or ischemic tissue. And so with each staple design 1656
change there's a knowledge gap that's potentially dangerous and frequently, and I know 1657
Covidien is very good at training but I don't think that's the case across the board. 1658
Frequently, surgeons get basically a lock room demonstration of the stapler. And I have 1659
a label to read and a 1-800 number to call if they have problems in the operating room. 1660
1661
And it may not be ideal across the board for all surgeons that are using these more 1662
complicated staplers. With the increased popularity of minimally invasive surgery and 1663
robotic surgery, I think there's an increase in the staple -- stapler use and what I'm 1664
concern about is there's an increase reliance on the stapler to complete the surgical 1665
procedure. And currently, there are no requirements for manufacturers to conduct device 1666
usability and labeling comprehension studies. And so I think that may be an area where 1667
we can improve and that can come with classifications of Class II. 1668
1669
The complications are devastating. Anastomotic leak, for example, occurs in different 1670
frequencies and different parts of the GI tract, probably higher in the rectum and soft 1671
genital (ph) areas. But the bottom line, it was also in peritonitis sepsis, sometimes 1672
multisystem organ failure and death, but more frequently it results in multiple invasive 1673
procedures for these patients, reoperation and diversion with the stoma, which is 1674
frequently permanent in these patients. And in those that undergo stomach closure, it's a 1675
difficult reoperation with yet another opportunity for an anastomotic leak or abdominal 1676
wall hernia formation. 1677
1678
These patients experience increased hospital stays, need for skilled nursing facility, 1679
sometimes long-term IV and nutrition, and compromised cancer prognosis. It's the 1680
anastomotic leak that can lead to that. There's a lot of literature on that, so I think that's 1681
an important point to consider when we have leaks. 1682
1683
Compromised quality of life, both short and long-term. It's sort of the gift that doesn't 1684
stop giving. And so bleeding -- excuse me, I went two slides. Bleeding can be acute or 1685
delay. It's frequently delayed when it's bleeding from the gastrointestinal tract. It can be 1686
intraluminal or extra -- more insidious extraluminal into the abdominal cavity. The 1687
patient can hold their entire blood volume in the abdominal cavity. 1688
1689
The risk I think maybe potentiated with the use of NSAIDs, which our antiplatelet drugs 1690
over opioids in the postoperative period for pain control, our populations becoming 1691
increasingly elderly and the use of antiplatelet drugs and anticoagulations is more 1692
prevalent and are increasingly elderly population. All these things can lead to increased 1693
bleeding from the staple line and I think if we can do better there, it's going to help 1694
improve public safety. 1695
1696
39
The consequences of bleeding from the staple line, unfortunately, are to make the line -- 1697
staple line ischemic and maybe increase the risk of anastomotic leaks area between the 1698
rock and hard place is a difficult problem. Early recovery after surgery pathways, great 1699
stuffs, allows patients to go home a couple of days after their bowel surgery. Most do 1700
well, however it's at the cost of the surgeon's ability to monitor them in a controlled 1701
setting. And those that have problems are more likely to return with severe anemia or 1702
late stages of sepsis with increase mortality, and I think that's a real issue. And for these 1703
reasons and others, FDA believes that the safety of internal stapler should be held to a 1704
higher testing standard than those staples as far as the 1990. 1705
1706
So the FDA conducted a systemic review to determine the occurrence of malfunction 1707
surgical staplers and describe the types of malfunctions, and witnessing the operating 1708
room and identify some of the acute consequences of those malfunctions. And it was the 1709
PubMed and EMBASE electronic database search from the dates of their inception to 1710
May 30, 2018 using terms related to stapler malfunction. The search was limited to 1711
publications of human studies and in English. Conference abstracts were excluded. And 1712
eligible studies included clinical trials, observational studies, systemic reviews and case 1713
reports. 1714
1715
And it yield to 378 records, 49 of these were retained and underwent full-text review and 1716
of those 40 were retained for data extraction. And the procedures in which surgical 1717
staplers were used included both open and laparoscopic kidney, liver, lung, 1718
gastrointestinal system and their associated blood supply. 1719
1720
And the occurrence of surgical stapler malfunction in the studies range from zero to 19 1721
percent of patients’ experience, 19 percent with the median of 1.8 percent of patients and 1722
0.1 to 5.2 percent of all stapler deployments had an episode of malfunction that can be a 1723
varying severity. 1724
1725
Survey of surgeons were conducted in some of these studies and up to 73 percent of 1726
surgeons said they experienced -- had personal experience in stapler malfunction and 86 1727
percent reported knowing surgeons who had either misfire or experienced stapler 1728
malfunction. There were 207 surgical stapler malfunctions reported and 195 included the 1729
type of malfunction. 1730
1731
The most common type of malfunction was staple malformation or staple line 1732
malformation at 32 percent, followed by staple line not forming or missing staples, i.e., 1733
fired staple is nice work but it didn't close the bowel or it didn't close the blood vessel on 1734
your release, you got stool in the abdomen or uncontrolled hemorrhage and that's a bad 1735
problem. 1736
1737
And of the literature search, that was 19 percent of the types of malfunctions that were 1738
reported. Other malfunctions reported included stapler locking, jamming, tissue damage 1739
or leaks, misfires, staplers not cutting, cartridges not loading and stapler breaking. 1740
1741
40
Consequences of intraoperative stapler malfunction were reported for 124 patients out of 1742
the 207 malfunctions identified. The adverse events included elective conversion from 1743
laparoscopic open in 10 percent, hemorrhage in 9.7 percent, and then emergent 1744
conversion from laparoscopic to open because of hemorrhage in about 4 percent. And 1745
then 75 or about 76 percent of the malfunctions "had no major consequences" where the 1746
intraoperative problems were managed by surgical techniques such as re-stapling or 1747
suturing. And when I read that, what came to mind was the point in the low anterior 1748
resection under the drapes, we're ready to fire the stapler after really long case. 1749
1750
The OR team is tired and I'm hoping for a good crunch and two complete donuts and the 1751
negative bubble test and then I find a leak and realized that the operation is going to be 1752
even longer. I need to find the exact point of the leak. Laparoscopically, it can difficult 1753
down deep in the pelvis where you don't have a lot of mobility of the anastomosis. 1754
1755
Do I suture the leak? Am I confident about that being point of the leak? Do I suture and 1756
divert? Do I redo the anastomosis increasing the risk of a foreshortened bowel and 1757
tension at the staple line having to then mobilize the bowel and hoping I don't cause 1758
ischemia? All those things came through in my head as I read that and somehow no 1759
major consequences and pay justice with the actual challenge of these intraoperative 1760
problems resulting from failed staple lines. 1761
1762
So to conclude, I think classifications of internal staplers improves FDA's oversight of 1763
the modern risk device and improves our area of regulatory weakness, and I think it's 1764
necessary. So Karen Nast will now present the MDR analysis and Dr. Rimmer will lead -1765
- subsequently give us how we're going to do this by improving stapler safety through 1766
special controls. Thank you. 1767
1768
LEWIS: Thank you. Before we proceed, we'll have a brief session for questions. I 1769
wanted to lead-off because it seems to me that the ability to recognize some aspect of 1770
malfunction or failure of the stapler is far more difficult laparoscopic surgery and open 1771
surgery and it would be much more likely that identification of leaks, for example, would 1772
be a delayed recognition a day or two later when the patient will get sick from it and 1773
would consequently have much greater morbidity. Do you have any data on that and the 1774
specific differences in those two? 1775
1776
GIBEILY: I don't, Dr. Lewis, at this point. I know it can happen anywhere from 1 1777
percent to 30 percent of the time in different areas of the GI tract, but I'm not sure. 1778
Recognizing the operating room versus recognize postoperatively, I don't have that data 1779
right now. I'll get back to you. 1780
1781
LEWIS: With the circular staplers, you have, as you alluded to, the presence of two 1782
complete rings to ensure that it function properly. You don't have that with the other 1783
types of staplers. So it would be more difficult to recognize, I would think. 1784
1785
41
GIBEILY: Absolutely, absolutely. And I think, you know, it really comes down for me 1786
as I read through these literature, I learned a lot a lot of things I didn't know when I was 1787
practicing as a general surgeon, as to how much time to wait to get that tighter B 1788
configuration after I, you know, tightened down to the firing zone. There's a Japanese 1789
who said wait five minutes and you can increase the strength -- the per strength of the 1790
staple line by two to threefold than if you went right away with stapling. 1791
1792
So a lot of these little tricks need to made better -- made better known to surgeons, I 1793
think, across the board and I think we need to reach out. I think the stapler companies 1794
need to, not only go to the ivory towers and talk to surgeons who are in a teaching 1795
position, but they need to out into the community surgeon and maybe offer courses or 1796
maybe they should be mandatory courses, I don't know. We don't regulate that 1797
specifically but ... 1798
1799
LEWIS: Yes. 1800
1801
GIBEILY: ... you know, there is room for improvement, I think. 1802
1803
LEWIS: The problem is the FDA can't really mandate anything in the way of ... 1804
1805
GIBEILY: Right. 1806
1807
LEWIS: ... physician training. Other questions, Dr. Levy. 1808
1809
LEVY: Elliot Levy. Thank you. I have a question related to previous speaker's 1810
comment about the application of retrospective special controls to devices with long 1811
histories. Can you estimate for us a number or proportion of the stapler devices that are 1812
currently used that might qualify or might be considered under that -- those conditions? 1813
1814
GIBEILY: You know, the main stapler companies are already doing the special controls 1815
that we're hoping to implement which is good news. It's just not across the board. There 1816
are questions as to, you know, what testing we want consistently, for example preclinical 1817
testing n animals. We don't always get that consistently. 1818
1819
So this will help us in that regard, I think, to kind of level the playing field across the 1820
board so that we can get input. And sometimes clinical testing, if there is a change in the 1821
staple tissue interactions such that it can raise a new risk, we may ask for clinical testing 1822
with Class II designation for staplers. 1823
1824
LEVY: My question though is, as we're considering the application of retrospective 1825
special control, how many devices or type or proportion would we be considering? 1826
1827
GIBEILY: Dr. Elliot Levy, let me make sure I understand the question. Are you saying 1828
going back to stapler is already on the market and then asking them to meet special 1829
controls? 1830
42
1831
LEVY: Yes. 1832
1833
GIBEILY: I don't have an answer to do that. 1834
1835
LEVY: If understood the previous comment it was some of those should be excluded 1836
because of the long history, global history. 1837
1838
GIBEILY: Right. 1839
1840
LEVY: And I'm wondering how many devices might qualify for that consideration? 1841
1842
GIBEILY: I think Dr. Kraus probably has an answer for you. 1843
1844
KRAUS: Well, I can give you an idea of what we would look at. I can't tell you how 1845
many. We've had hundreds of clear 510(k's) for staples. Some of them included a stapler 1846
back in -- I think 1988, we exempted staplers so there were staplers cleared before that 1847
which we did see the data for the stapler. However, the idea is that working with industry 1848
and others, we will come up with a list of what we consider our special controls and those 1849
will be discussed and put up on the screen a little bit later. 1850
1851
Medtronic already put some of them up and you have a chance to look at them. And 1852
what we'll do is we'll say, OK, so these are the critical factors and we will go and look 1853
back to see if those previously clear devices have that type of data. And if they do, then 1854
probably we don't need to ask them anymore questions. If they don't, then, you know, we 1855
may want to ask them questions. However, they might be able to answer those questions 1856
without necessarily doing new tests. They may have clinical data. They may have 1857
animal data. They may have data, you know, that they have collected over the years that 1858
they can provide that shows that they met the special controls. 1859
1860
LEWIS: Dr. Posner. 1861
1862
POSNER: Philip Posner. In your data collection, have you come across amount of data 1863
on use in neonatal and congenital corrective procedures? 1864
1865
GIBEILY: I did not. We didn't review that data specifically to my knowledge. 1866
1867
POSNER: Because if we ... 1868
1869
GIBEILY: I'm involved in the team but I did not see that in the review. 1870
1871
POSNER: Because if we are developing guidelines for type 2, do we want to look at 1872
something special for neonatal cases where you're dealing with incredibly fragile 1873
connective tissue and add data to the sub-topic. 1874
1875
43
KRAUS: So for devices that are indicated specifically for pediatric use those would 1876
come under more scrutiny and we would look at those differently than we look at devices 1877
that are intended for adults. 1878
1879
LEWIS: Dr. Bloom. 1880
1881
BLOOM: We use the term surgical stapler to encompass of a variety different devices 1882
that are really intended to do a variety of different things. The linear staplers are used to 1883
either cut blood vessels which aren't supposed to bleed or push on a pancreatic tail and 1884
hopefully it doesn't leak a week later or reanastomosis bowel and provide a framework 1885
that doesn't strangulate blood that allows for ingrowth and scouring. Yes, my impression 1886
is the reason we're all sitting here today is because of a profundity of failure with circular 1887
staplers, which only have really one difficult role in working with the most difficult tissue 1888
types to conduct an arterio-arterial anastomosis. Do you think that the stapler types 1889
should be -- a linear stapler and a circular stapler should be treated the same way? 1890
1891
GIBEILY: You know, I think both should be treated the same. As of now, they both 1892
have potential risk and, thankfully, not necessarily a frequent risk but they are life-1893
threatening for sure. And so I think whether it's a leaking anastomosis and patient comes 1894
in late and sepsis goes into multisystem organ failure or insidious bleeding versus 1895
bleeding in the operating room where you're struggling to get into the chest or the 1896
abdomen to stop the bleeding and the patient bleeds to death or as a result of the direct 1897
bleeding or the consequences of, you know, the bleedings of postoperatively. You know, 1898
there are still -- both are life-threatening and both need to be scrutinized I think as of now 1899
in the same way whether it's a linear stapler or circular stapler. 1900
1901
A linear stapler go across the pulmonary artery, whereas circular stapler creating 1902
anastomosis in the colon and rectum. 1903
1904
BLOOM: I guess my point is I would imagine that failures from circular staplers aren't 1905
due to stapling -- well, are purely a bowel or leakage problems, not bleeding problems. 1906
1907
GIBEILY: Right. 1908
1909
BLOOM: And probably aren't coming across a clamp that might be a linear stapler, 1910
might be a staple line. And for that reason, should -- not the classification issue, but 1911
should these different types of stapler have different levels of strength (ph) problem? 1912
1913
GIBEILY: Very possibly. And, you know, there's the beauty of Class II designation that 1914
allows us to make that distinction as we review the submissions to see if they meet 1915
additional clinical studies, for example, or additional animal studies, you know. And 1916
we're looking at things like perfusion of the anastomosis now which is not frequently 1917
intraoperatively or that may ought to be part of the preclinical studies for these staplers. 1918
So yes, I think this gives us that option with your classification. 1919
1920
44
LEWIS: Dr. Miller. 1921
1922
MILLER: Thank you. Mike Miller here. One of the comments from our Medtronic 1923
representatives was that they didn't feel that we need to include in the risk of the staplers 1924
cancer occurrence. How do you feel about that? 1925
1926
GIBEILY: No, I don't know if it's a risk of the stapler specifically but it's certainly a risk 1927
that's been reported, not in prospective. It's been a large retrospective says in 1928
metaanalysis than a leak -- anastomotic leak does increase the risk of local reoccurrence 1929
by two to threefold and decreases cancer-free survival about anywhere from 20 to 30 1930
percent. I've got those studies, I've had go through them a number of times and so I think 1931
that is real. It's not -- again, it's not necessarily Level 1 evidence but it's a real concern, 1932
so much so that we're even looking at subclinical leaks and, you know, anastomotic 1933
sealing for example to prevent them in such things to impact that very concern, that very 1934
problem. 1935
1936
LEWIS: Thanks, Dr. Gibeily. We now need to move ahead. 1937
1938
GIBEILY: Thank you. 1939
1940
LEWIS: We'll next hear from Ms. Karen Nast regarding the medical device reporting for 1941
surgical staplers. 1942
1943
NAST: I'm Karen Nast from the Division of General Surgery Devices in CDRH. I'm 1944
going to provide an overview of the MDR data for surgical staplers. 1945
1946
Although MDRs are a valuable source of information, this passive surveillance system 1947
has limitations, including underreporting, data quality issues like the potential submission 1948
of incomplete, inaccurate, untimely, unverified, or biased data, limitations of the MDR 1949
regulation. Lack of MDRs does not necessarily mean there are no problems. It is not 1950
possible to definitively determine a causal relationship between an event and a device 1951
based on MDR data alone. 1952
1953
Finally, the incidence or prevalence of an event cannot be determined from this reporting 1954
system alone due to potential under-reporting of events and lack of information about the 1955
total number of devices. 1956
1957
Individual MDRs for surgical staplers for internal use are reported through FDA's MDR 1958
database, which houses mandatory reports from medical device manufacturers, importers, 1959
user facilities, as well as voluntary reports from entities such as health care professionals, 1960
patients, and consumers. 1961
1962
Prior to February 2019, surgical staplers for internal use were also eligible for the ASR 1963
Program. The analysis of MDRs associated with surgical staplers for internal use 1964
45
provided herein includes all events received by FDA through the standard individual 1965
MDR reporting mechanism as well as through the ASR Program. 1966
1967
Sorry. This graph shows all the medical device reports of surgical staplers for internal 1968
use broken down by year. All adverse event reports received between January 1, 2011 1969
and December 31, 2018 for product codes GAG and GDW were searched. Because 1970
surgical staplers are used together with staples as a system, all adverse event reports were 1971
searched using the surgical staplers for internal use product code GAG and the surgical 1972
staples for internal use product code GDW to obtain a comprehensive picture of the 1973
safety profile for surgical staplers for internal use. There are 412 deaths, over 11,000 1974
injuries, and over 98,000 malfunctions. 1975
1976
The most commonly reported device problems include failure to fire, misfire, failure to 1977
form a staple, difficult to open or close, break/detachment of device component, or the 1978
device operates differently than expected. The most commonly reported patient problem 1979
includes tissue damage, hemorrhage, blood loss/bleeding, failure to anastomose, and 1980
delayed surgical procedure. 1981
1982
This graph shows the number of injury reports received each year. 1983
1984
A sampling of injury MDRs filtered by the top 5 device problem codes were analyzed. 1985
Although the MDRs were spread throughout different device problem codes the failures 1986
were similar leading to similar outcomes. Mechanical malfunctions including the device 1987
cutting the tissue without deploying staples, misfiring of the device leading to incomplete 1988
staple lines and malformed staples may cause prolonged surgical procedures or 1989
unplanned, additional surgical procedures, bleeding, sepsis, fistula formation, tearing of 1990
internal tissues and organs, and anastomotic leak. 1991
1992
Whether the device failed to fire or misfired, a device component detached or broke, 1993
failed to form staple, operated differently than expected or the device was difficult to use 1994
the result seen most frequently was a staple line that was not complete. Failure to 1995
anastomose is most often what leads to converting to an open procedure, changing the 1996
procedure, creating an ostomy, loss of tissue, bleeding, blood transfusions and extended 1997
surgical time. 1998
1999
This graph shows the number of death reports received each year. Seventy-two percent 2000
of the death reports involved a linear stapler and 17 percent involved a circular stapler. 2001
The most commonly reported procedure types in the death reports include cardiothoracic, 2002
bariatric, hindgut, and solid organ. 2003
2004
Sixty-four percent of the MDR reports some type of wound dehiscence, either the staple 2005
line opened, it did not form well or the staples were misshapen. Fourteen percent of the 2006
reports -- report, the stapler failed to fire or fired and cut but did not deploy staples. Of 2007
the 412 death reports, 233 provided information to calculate the time between the initial 2008
46
surgery and the patient death. Of those, 30 percent of the deaths were intraoperative and 2009
52 percent of the deaths occurred within 7 days postoperatively. 2010
2011
Thank you. 2012
2013
LEWIS: I have a question. Generally, your data regarding injuries and deaths seems to 2014
show an increase over the last three to four years, whereas the presentation that we heard 2015
from Medtronic shows a general decrease. Can we infer from that that there's a 2016
difference in the behavior of devices from the other manufacturers, the Medtronic? 2017
2018
NAST: This data includes all the manufacturers. I don't remember if Medtronic 2019
provided their reportable MDR numbers or their complete numbers. 2020
2021
LEWIS: Well, the difference is they have a denominator so they can calculate a rate for 2022
the staplers they supply. You don't have that with MDR so you wouldn't be able to 2023
calculate a meaningful rate. But in terms of absolute numbers, there seems to be a 2024
divergence in the reports in terms of the trends in the last three years. 2025
2026
Dr. Hicks. 2027
2028
HICKS: Yes, Hicks. Also, I just wanted, if you're just -- once you click this data and of 2029
course the numbers I'm looking at that you show two months ago were less by a lot. I 2030
mean, you know, there's another thing that – (INAUDIBLE) published two months ago 2031
were less than this by a lot. 2032
2033
NAST: This data includes the ASR reports as well as individual reports. 2034
2035
LEWIS: I see no other questions. Thank you very much, Ms. Nast. 2036
2037
NAST: Thank you. 2038
2039
LEWIS: Dr. Dale Rimmer will now present for the FDA to describe the current testing 2040
methods and propose risk mitigations and special controls, which are being proposed for 2041
surgical staplers. Dr. Rimmer. 2042
2043
RIMMER: We'll now hear a short description of the current review practice for surgical 2044
staplers and the implantable staples. As Class I devices, surgical staplers in normal use 2045
are exempt from 510(k) review. However, surgical staplers are also in bundled together 2046
with Class II implantable staples in 510(k's) admission. During the 510(k) review, 2047
staplers are considered only in the context of their support of the implanted staple. 2048
2049
Current review practice for implantable stables includes evaluating performances that are 2050
provided for the implanted staple with the assumption that the characteristics of the staple 2051
line are manifestation of the staple's ability. Testing of the stapler is only evaluated when 2052
the stapler is provided along with the 510(k) for the staple. 2053
47
2054
Typical testing includes staple line evaluation following worst case deployment 2055
conditions, such as deployment into thick and thin tissues, as well as pressurization to 2056
failure of the staple line. Additionally, sterilization data for the staple and stapler is 2057
provided as well as data support in the biocompatibility and a more compatibility of the 2058
implanted staple. 2059
2060
When needed to support the substantial equivalence of the staple and when models are 2061
provided to show acute hemostasis. In some reviews a chronic animal survival study is 2062
provided to evaluate healing and to evaluate parameters such as subchronic leaks via 2063
histopathology. In essence of this testing also supports stapler performance. 2064
2065
We'll now discuss the risks, mitigations and special controls that have been identify for 2066
internal surgical staplers. The FDA has identified risks posed by internal surgical staplers 2067
and FDA proposes these risks can be mitigated by various testing and labeling 2068
requirements. These mitigation measures are the basis for the special controls that will 2069
be discussed on the following slides. 2070
2071
A summary of the risks and mitigation measures are shown in this table. Risks include 2072
device failures or malfunctions that may result in prolonged surgical procedures or 2073
unplanned surgical interventions which may lead to complications such as bleeding, 2074
sepsis, fistula formation, tearing of internal tissues and organs, increased risk of cancer 2075
recurrence, and death. FDA proposed that this risk can be mitigated by performance 2076
testing and labeling evaluations special control. 2077
2078
Use error may result from a device design that is difficult to operate and/or labeling that 2079
is difficult to comprehend. For example, user difficulty in firing the stapler may result in 2080
staples not being fully deployed, and misfiring may result in staples being inadvertently 2081
applied to the wrong tissue. Inadequate instructions for use may result in selection of 2082
incorrectly sized staples for the target tissue. 2083
2084
When staples are applied to the wrong tissue or when incorrectly sized staples are 2085
applied, staples are unable to properly approximate the underlying tissue, resulting in 2086
tissue damage, anastomotic leakage, and bleeding. This in turn, may lead to more severe 2087
complications, such as abscess, sepsis, peritonitis, hemorrhage. FDA proposed that this 2088
risk can be mitigated by usability testing, labeling comprehension studies and labeling 2089
special controls. 2090
2091
Another risk is the occurrence of an adverse tissue reaction. If the patient-contacting 2092
materials of the device are not biocompatible, local tissue irritation and sensitization, 2093
cytotoxic, or systemic toxicity may occur when the device contacts sterile tissue. The 2094
FDA proposed that this risk can be mitigated by a biocompatibility evaluation. 2095
2096
Finally, there is a risk of infection that may result from stapler use and may occur if the 2097
device is not adequately reprocessed or sterilized. The device may introduce pathogenic 2098
48
organisms into sterile tissue and may cause an infection in a patient. FDA proposes that 2099
this risk can be mitigated by leveling sterility testing and shelf-life evaluations. 2100
2101
The FDA proposes the following special control. To assess the device's performance, 2102
performance testing must demonstrate that the stapler, when used with compatible 2103
staples, performs as intended under anticipated conditions of use. Performance testing 2104
must include an evaluation of staple formation characteristics in maximum and minimum 2105
tissue thicknesses for each staple type, in measurement of the worst-case deployment 2106
pressures on stapler firing force, in measurement of staple line strength, confirmation of 2107
staple line integrity; and in vivo confirmation of staple line hemostasis. 2108
2109
Usability testing and a labeling comprehension study must demonstrate that the clinician 2110
can correctly select and use the device, as identified in the labeling, based on reading the 2111
directions for use. 2112
2113
For biocompatibility, the elements of the device that may contact the patient must be 2114
demonstrated to be biocompatible. For sterility, performance data must demonstrate the 2115
sterility of the device. Labeling must include validated methods, instructions for 2116
reprocessing any reusable device components. And validation of cleaning and 2117
sterilization instructions must demonstrate that any reusable device components can be 2118
safely and effectively reprocessed according the recommendations of the cleaning and 2119
sterilization protocol in the labeling. 2120
2121
For shelf-life performance data must support the shelf life of the device by demonstrating 2122
continued device functionality, sterility, and package integrity over the identified shelf 2123
life. 2124
2125
Labeling of the device must include each of the following, a list of contraindications 2126
regarding the use of the device on tissues for which the risk of stapling outweighs any 2127
reasonably foreseeable benefit due to known complications. Labeling must include 2128
appropriate warnings regarding how to avoid known hazards associated with device use. 2129
The device labeling must include a list of staples with which the stapler has been 2130
demonstrated to be compatible. 2131
2132
Additionally, labeling must identify key performance parameters and technical 2133
characteristics of the stapler and the compatible staples needed for safety use of the 2134
device. Labeling must include information regarding tissues on which the stapler is 2135
intended to be used. And packaging labels must include critical information and 2136
technical characteristics necessary for proper device selection. 2137
2138
After reviewing the available evidence, the FDA believes that general controls are 2139
insufficient provide a reasonable assurance of the safety and effectiveness of surgical 2140
staplers for internal use. However, FDA has determined that there is sufficient 2141
information to establish special controls to provide such assurance. FDA believes that 2142
surgical staplers for internal use are of substantial importance in preventing impairment 2143
49
of human health but do not present a potential unreasonable risk of illness or injury when 2144
intended to deliver compatible staplers to internal tissues during surgery for resection, 2145
transaction and creating anastomoses. Are there questions? 2146
2147
UNKNOWN: I'm hearing now the term under reported a lot, and I've seen it there's an 2148
increase in the data from FDA about adverse reactions. How would FDA feel about our 2149
registry that includes patient reporting, physician reporting and everybody has access to 2150
him? 2151
2152
RIMMER: I think that use of registry is something that we would be willing to consider 2153
and that is the recommendation on the panel. 2154
2155
LEWIS: Mr. Posner? 2156
2157
POSNER: We've already heard a lot about labeling and that was not always written in 2158
followed. And we also know with recent, the drive field, there's off label use of items. 2159
And does the FDA have a way to follow up on user compliance with label instructions? 2160
2161
LEWIS: Mr. Kraus, do your respond? 2162
2163
KRAUS: Yes, I'm sorry. 2164
2165
POSNER: It's just the question of whether you can follow up on user compliance as 2166
labeling instruction based on the fact that a lot of people don't read the labels, and it may 2167
also be off label use of specific devices just (INAUDIBLE) with drugs. 2168
2169
RIMMER: Well, you know, so a position surgeon who is going to use a stapler as long 2170
as it, you know, an approved or clear device can use it anyway that they feel is 2171
appropriate. The manufacturer however is limited and how they can promote the device. 2172
So, the manufacturer if they know that the device is not indicated for a certain use, if they 2173
go out and promoted for that use the FDA can act. 2174
2175
If a surgeon uses the device for a certain procedure and is successful using that device, 2176
even if the device is not indicate for that they can go to our meeting and they can present 2177
that information as long as a manufacturer is not paying them to do so. So, you know, so, 2178
you know. 2179
2180
But as far as, you know, making people read the instructions for use. You know, we've 2181
seen cases where we get information that there's a certain problem with a certain device 2182
and we know that the instructions and the warnings, and the labeling clearly says don't do 2183
that. So, when we see multiple reports, we can put out to your doctor letters, letters that 2184
we send to the administrator of hospitals saying, you know, make sure your people read 2185
this before they use this device. We do public announcements on our website. We, you 2186
know, our commissioner that just retired dr. Gottlieb, he like to do tweets. 2187
2188
50
So we do try to find different ways of getting the information out there encouraging 2189
looking at the labeling and reading the instructions but there's no way we can twist arms 2190
and force people to do that. And so, does that answer your question? 2191
2192
LEWIS: Other questions. Dr. Pories? 2193
2194
PORIES: What is the number of quality control when manufacturer is out towards to 2195
different company because they want to achieve that? 2196
2197
RIMMER: Why can't speak for health company is outbreak their quality system for, you 2198
know, it produce a rumor that the stapler is being Class I devices may or may not be 2199
subject to you. They may or may not be subject to you the same quality of control 2200
system as a Class II product with it. 2201
2202
PORIES: Is this some problem in terms of quality control? 2203
2204
RIMMER: Right. So, you know, the intuitive answer is that increased levels of quality 2205
control are condemned. So, can I interject? There are a -- in our, you know, 21 CFR 2206
there are a list of what we consider, you know, quality systems that every company that 2207
has a device that they manufacture needs to adhere too. And that includes quality 2208
control. And every company needs to keep records on their quality control and how well 2209
they manufactured devices. And when the FDA comes out to inspect, they will look at 2210
those records. 2211
2212
Make sure the company is keeping those records, keeping all the records they are 2213
supposed to. And if you remember Ms. Shulman's earlier, she talked about that as record 2214
keeping and those various things that are part of quality control systems. What is not 2215
included in that are the special controls that we've just presented where the company for, 2216
you know, doing usability studies getting -- making sure the instructions for use are 2217
understood all of those other factors that are not included in the quality system would 2218
also be incorporated into their process. And that some companies do and some don't. 2219
And by up-classifying these devices to Class II, we would assure that they are looking at 2220
those other factors as well. 2221
2222
LEWIS: Thank you. All right, thank you, Dr. Rimmer. 2223
2224
To summarize the morning, sure not to end of, it seems to me the FDA has presented the 2225
many arguments for the up-classification of the devices from Class I and Class II. And it 2226
appears that the FDA is -- and Medtronic are basically in valiant agreement about that. 2227
And Medtronic is already been pursuing that in their marketing. 2228
2229
As far as I know, we do not have representatives from the other two major companies 2230
who make staplers for this hearing. And we don't know if they're not interested in that or 2231
if they don't have any problems. We don't know what their position is on this. Ms. 2232
Pawelski as industry representative, do you have any information at all from them? 2233
51
2234
PAWELSKI: I don't have any official statement from either of the other two companies 2235
now. 2236
2237
LEWIS: OK, thank you. So, we really don't know the positions of the other companies. 2238
We have to proceed this afternoon without the information in regard to that. We're at the 2239
end of the morning. When we reconvene, there will be an open public hearing. 2240
2241
Currently, we have five people signed up for that Mr. Jack Mitchell, Dr. Sandeep 2242
Khandhar, Dr. Ronit Yarden, Dr. Aurora Pryor and Dr. Michael Seger. Each of you will 2243
have minute presentation when we reconvene. If there are any other members who wish 2244
to present testimony during the public hearing, please register immediately after this 2245
session either with Commander Garcia or with myself so that we know you want to 2246
speak. Otherwise, we won't have any other fledge to participants. Those presentations 2247
again will be limited to five minutes. 2248
2249
We're going to break for lunch now. Since we're running about 30 minutes earlier, we 2250
will reconvene 30 minutes early at 12:30 rather than at 1 o'clock to allow us 45 minutes. 2251
And for members of the panel, there's a buffet available for $12.95 in the Merlan room on 2252
the 8th floor of hotel which you can partake of. Lastly, I would ask the panel members, 2253
do not discuss the meeting either amongst to yourselves or with members of the audience 2254
during the break. 2255
2256
Thank you all to the presenters. I call the meeting back into session. And before we get 2257
started with the open public hearing, Ms. Pawelski will have an announcement regarding 2258
the participation of Ethicon. 2259
2260
PAWELSKI: So, I did hear from Ethicon over the break and they do agree that the 2261
stapler should be treated as Class II devices and that is consistent with their current 2262
practice as well. 2263
2264
LEWIS: Great, thank you very much. 2265
2266
PAWELSKI: Thank you. 2267
2268
LEWIS: We'll now move to the open public hearing. And we'll go in order of the people 2269
who have registered starting with Mr. Jack Mitchel, the Director of Health Policy for the 2270
National Center for Health Reserve … 2271
2272
GARCIA: I got the read a statement first. 2273
2274
LEWIS: I apologize. Commander Garcia needs to read the statement first. 2275
2276
GARCIA: Thank you, Dr. Lewis. Thank you, Dr. Lewis. About the (ph) Food and Drug 2277
Administration and the public believe in a transparent process for information gathering 2278
52
and decision making. To ensure such transparency at the open public hearing session of 2279
the advisory committee meeting, FDA believes that this is important to understand the 2280
context of an individual's presentation. 2281
2282
For this reason, FDA encourages you, the open public hearing speaker, at the beginning 2283
of your written or oral statement to advice the committee of any financial relationship 2284
that you may have with any company or group that maybe affected by the topic or this 2285
meeting. For example, this financial on commission main include companies or group's 2286
payment of your travel, lodging or other expenses in connection with your attendance at 2287
the meeting. 2288
2289
Likewise, FDA encourages you at the beginning of your statement to advise the 2290
committee if you do not have any such financial relationships. If you choose not to 2291
address this issue the financial relationships at the beginning of your statement, it will not 2292
preclude different speaking. Thank you, Dr. Lewis. 2293
2294
LEWIS: We have five speakers who have registered. You each have five minute limit 2295
on your discussions. And I ask all of you after presentation to please remain seated on 2296
the front row up here because at the end of all the presentations, we will have any 2297
questions from the panelist for all five members. And if anyone else which is to speak 2298
that is not registered, we will recognize you and you would have three minutes to make 2299
some more presentations before we proceed to the questions. 2300
2301
So, we'll go back to Mr. Jack Mitchell who's a Director of Health Policy, National Center 2302
for Health Research. 2303
2304
MITCHELL: Now, good afternoon and thank you for the opportunity to speak. As I was 2305
introduced, I'm Jack Mitchell, I'm with the National Center for Health Research. NCHR 2306
is a non-profit think tank that conducts and analyses research with implications for public 2307
health including the safety and effectiveness of medical products. 2308
2309
We accept no money from the pharmaceutical or medical device industries and I 2310
therefore have no conflicts of interest to report. NCHR strongly supports FDA's draft 2311
guidelines to reclassify from Class I to Class II, certain surgical staplers for internal use. 2312
We believe that the agency has uncovered more than sufficient evidence if it's reviewed 2313
to make such a reclassification absolutely necessary and in fact overdo. 2314
2315
And the fact that two of our three major manufacturers, Medtronic and Ethicon agree 2316
with the agency that these devices should be class to leaves less room for controversy and 2317
argument that we may have thought at the beginning of the day. 2318
2319
On March, Kaiser Health News published to disturbing article entitled "Hidden FDA 2320
reports detail harm cause by scores of medical devices." This article revealed that the 2321
number of serious adverse events reported for surgical staplers and other medical devices 2322
was much higher than previously known the physicians or surgeons or the public. In fact, 2323
53
many thousands of such adverse events had been hitting from the public and an FDA 2324
database containing what agency officials referred to as a registry exemption. 2325
2326
Now, under this previous policy, a medical device manufacturer could applaud FDA to 2327
(INAUDIBLE) as many of thousands of adverse reports and summaries were not 2328
available to the public. It doesn't driven hundreds of this adverse events were sometimes 2329
bundled into one single report or a few reports. In 2016 according to a Kaiser article, 2330
only 84 injuries are malfunctions or identified in the public databases have been 2331
contributed to surgical staplers or staplers used in them. 2332
2333
Meanwhile, thousands of additional stapler related malfunctions were included in the 2334
non-public database. Reporting the information FDA provided the Kaiser Health News. 2335
2336
The article also quoted a form array of FDA commissioner stating that he was unaware of 2337
the non-public database reporting system. Now, in fairness, FDA is informed due that 2338
they cease these practices of February. And indeed, it may have been an originally 2339
legitimate practice to try to limit unnecessary repetitive reviews and people work. 2340
2341
But nonetheless, many tens of thousands of adverse events with health and public view 2342
when you're now just getting access to them, these adverse events included serious 2343
injuries cause to patients by malfunction or misuse of surgical staplers. These harms 2344
included critical adverse event such as life-threatening sepsis, infections, tearing of an 2345
internal organ and tissues, as in your package and staplers that malfunction doing 2346
surgery. 2347
2348
Since Class I devices are defined as low risk, such potentially fail medical calamities or 2349
clear evidence that staplers need to be up classified to Class II. And as you know Ethicon 2350
recently held a Class I recall of thousands of its own circular staplers. Surgical staplers 2351
are necessary and part of daily hospital operations as you all know better than me. 2352
2353
But as we now also know for the data, the malfunction are cause serious problems far too 2354
often to remain in a regulatory class was cotton swabs, tongue depressor or cratches (ph), 2355
one FDA official earlier today, like in their regulation to that of a toothbrush. These 2356
indeed are medical devices which are invasive and require much better safeguards. 2357
2358
We urge the committee to determine whether a special controls under the 510(k) program 2359
a pathway that does not require clinical trials or direct evidence of safety or effectiveness 2360
would be sufficient to adequately protect patients from defective devices. I might add 2361
that in 2011 the Institute of Medicine which is now part of the National Academy in 2362
Sciences concluded in a very strongly worded report to FDA with to 510(k) pathway 2363
through of neither safety nor efficacy. 2364
2365
The IOM report strongly recommended the FDA that it's proper discard the 510(k) 2366
pathway and replace it with a more rigorous approval system. FDA rejected those 2367
recommendations made minor changes to the 510(k) system which has been under 2368
54
critical fire in the national and international media in recent months to a point where 2369
formal Commissioner Gottlieb promised before he left office that there would be changes 2370
made to the system. It is not fantasy. 2371
2372
I respectfully ask you in conclusion to recommend that the FDA reclassify surgical 2373
staplers intended for internal use as Class II medical devices. Please also consider what 2374
else is needed to ensure that all such staplers in the surgical staplers used in them are safe 2375
and effective as possible. Thank you very much. 2376
2377
LEWIS: Thank you for your comments. Next turn to Dr. Sandeep Khandhar. He's a 2378
Thoracic Surgeon and a Virginia Cancer Specialist. Mr. Khandhar, you have five 2379
minutes. 2380
2381
KHANDHAR: Dr. Lewis, panel, guest, thank you very much. My name is Sandeep 2382
Khandhar. I'm a community thoracic surgeon operating in Northern Virginia. I am a 2383
paid consultant from Medtronic. I serve on their side to be advisory committee and I've 2384
been doing so for the past roughly decade. But I'm here with my only accord and in my 2385
own expense. 2386
2387
I'd like to start with just a short patient story. My entire career is governed by surgical 2388
staplers. I entered the field of thoracic surgery in 2006. And since that time my training 2389
has veered towards the minimal invasive practice. These practices allowed the following 2390
case scenario of a 35-year-old woman with lung cancer, two children, a runner and avid 2391
marathon runner, and someone who watched their father died of lung cancer just two 2392
years before that. 2393
2394
She herself was diagnose with four-and-a-half centimeter lesion in the right lower lobe at 2395
the central aspect and is told that she can only have an open to our academy because it 2396
wasn't comfortable enough for minimally invasive techniques and they hadn't progress. I 2397
saw her, we did a minimally invasive intervention on her. Six months after surgery after 2398
a bilobectomy, she ran a full marathon. She's run three since marathons. She's five years 2399
out from surgery. 2400
2401
This is just one case and many of you are surgeons and you have similar experiences of 2402
our successes. My entire career, I do over 100 and anatomic lung resections. You've 2403
heard of the potential mortalities from surgical stapler and misfires in the pulmonary 2404
space, where indeed it does lead to life-threatening hemorrhage. I agree. And every time 2405
I fire that stapler in a pulmonary vein, I wonder, is it going to fail this time? But I was 2406
trained in an era where -- my mentors trained me to think that staplers don't fail, surgeons 2407
do. 2408
2409
And I take that responsibility seriously. I know what I'm going to do if the stapler doesn't 2410
fire. If a stapler fails but it has not been my experience. These devices are robust. These 2411
devices have allowed us to progress the field. And these devices are necessary for the 2412
care of appropriately and appropriate delivery of healthcare in United States today. 2413
55
2414
Without these devices, we don't have alternatives in thoracic surgery. We're not going 2415
back to simply securing lung tissue with stitches. So, I think this is a foregoing 2416
conclusion that staplers are necessary. I agree. And I've sat with interest on morning 2417
listening to the talks about designation of Class II. And I agree, how can one ever refute 2418
the need for better safety and for better training? I do it every day. I do with every 2419
student. I do with every resident. 2420
2421
We need to train more. We need to be safer. We need to be better but we need to 2422
progress. 2423
2424
Dr. Lewis talked this morning about the shortage of surgical staplers because of 2425
manufacturing delays and processes. This has affected my practice. I've had to delay 2426
cases. I've had to delay patients because of a lack of availability of surgical staplers. 2427
2428
I would urge to this committee and I urge the FDA that, yes, we need to be safer. But the 2429
special controls that you imposed, please do them in collaboration with our industry 2430
colleagues. This needs to be a collaborative effort. I as a surgeon before you take full 2431
responsibility of the care in the patient that I operate on. This I don't ensure, but I rely 2432
upon my industry colleagues to provide me with tools that enable me to do my job and I 2433
rely on bodies like this to keep us safe. So I'll simply urge you to continue to collaborate 2434
and to make us all to safer together. Thank you very much. 2435
2436
LEWIS: Thank you. Let's turn to Dr. Ronit Yarden, director of Medical Affairs at 2437
Colorectal Cancer Alliance. Dr. Yarden, are you here? He is not. Next is Dr. Aurora 2438
Pryor, president of the Society of American Gastrointestinal and Endoscopic Surgeons. 2439
2440
PRYOR: Thank you, Dr. Lewis and the panel. Thank you for the FDA for the 2441
opportunities to speak today. My name is Dr. Aurora Pryor. I'm a minimally invasive 2442
foregut and bariatric surgeon and I'm the current president of SAGES, which is the 2443
Society of American Gastrointestinal and Endoscopic Surgeons. I'm here on behalf of 2444
SAGES and not sponsored by any of our industry partners. 2445
2446
SAGES is a group of over 7,000 members whose mission is to improve quality patient 2447
care through education, research, and innovation. We focus on gastrointestinal and 2448
endoscopic surgery. We are the largest minimally invasive surgical society and the 2449
second largest general surgery society in North America. 2450
2451
We're at the forefront of surgical innovation utilizing our members tens of thousands of 2452
hours of clinical experience to evaluate new advances in surgical techniques, which 2453
includes integration with surgical devices and using minimally invasive techniques that 2454
help enhance and shorten a patient's recovery time. 2455
2456
We have created numerous guidelines in how to treat multiple surgical diseases, help to 2457
evaluate, integrate and leverage technology in ways that benefit our patients, and are 2458
56
constantly evaluating and educating ourselves and others on ways on which we can 2459
improve the high quality surgical care that we already provide. 2460
2461
Three basic pillars of SAGES are clinical care, education and research. Our daily efforts 2462
utilized all three with the focus all we set on our surgical patients and ensuring they are 2463
provided with the best care possible. 2464
2465
The reason for my testimony today is to express our support and some comments 2466
regarding surgical staplers and how they are use in the operating room. To understand 2467
the use of staplers, you must understand what they are use for, dividing and securing 2468
tissues, resecting tissues and removing lesion safely. 2469
2470
Another major use of staplers is for bowel anastomosis. Let's focus for a moment on 2471
anastomosis. When resecting a piece of bowel and then reattaching the remaining ends, 2472
there are numerous factors that are come into play. 2473
2474
The health and quality of the tissues that are being brought together, the ability to make 2475
the anastomosis tension free in an attempt to minimize potential complications, the 2476
overall health of the patient and any medical comorbidities they may have and the setting 2477
in which the operation is being performed, whether it is emergent versus elective. These 2478
are just some of the clinical factors a surgeon must use when making the decision to 2479
create an anastomosis. 2480
2481
There are three main options you can use when making this anastomosis. You can 2482
handsaw the whole thing using sutures, you can use stapling devices, or you can use a 2483
combination of the two. Regardless of the approach you use, and even if you do 2484
everything perfectly, there is a risk of complications. There is no such thing as a perfect 2485
operation. There are always risk and no matter how hard we prepare to try and prevent 2486
them from happening, they can still happen. 2487
2488
In fact, studies of anastomotic complication showed at these techniques are essentially 2489
equivalent. Our job as surgeons is to minimize the risk to the best of our abilities and that 2490
is where our surgical judgment comes in the play. To single out a potential device that 2491
has been used for numerous years as a major contributor to complications, injuries and 2492
deaths put these devices in a false light. Nothing is done in a vacuum and the ultimate 2493
results are still base on the surgical decisions and patient factors before, during and after 2494
the operation. 2495
2496
Staplers play a large role in our surgical world and they enable us to quickly performs 2497
safe anastomosis in minimally invasive techniques to minimize more morbidity of 2498
surgery and allow our patients to return to work in an expeditious fashion. Many 2499
minimally invasive procedures today could not be safely performed without staplers. 2500
2501
Surgeons are driven by data. You heard detailed data from numerous people today. I just 2502
want to put that numbers the FDA released into perspective. You reported over 100,000 2503
57
individual medical device reports for seven year period from 2011 to 2018. These 2504
include 400 desks, 11,000 injuries and about 100,000 malfunctions. Some of these may 2505
be difficult to reports. But if you look at the number staplers that are fired both in the 2506
U.S. and worldwide, at most this is a 0.3 percent risk of complication. 2507
2508
In addition, the use of cartridges is also increasing year to year, so that rate of reports is 2509
relatively consistent. I understand the numbers are not exact, but I'm confident that you 2510
can see the trend that is developing. Given these numbers in isolation that can be done, 2511
but putting them in perspective should give us all some reassurance on the matter. 2512
2513
Do we wish we could have a zero percent rate of complications? Of course. Being able 2514
to go safely innovate allows us to continue to improve the quality and outcomes for our 2515
patients. The focus should be where it usually lies on ensuring that the surgeon is in good 2516
clinical judgment regardless of the device they may be using. We must also assure that 2517
surgeons know how to use these devices. 2518
2519
This is where stages comes in as well as other medical and surgical organizations. 2520
Through evaluation, education and innovation we can take our roles regarding patient 2521
safety and patient care very seriously and ensure that any changed is rigorously evaluated 2522
and embedded prior to widespread implementation. 2523
2524
We can be your partners in this endeavor. Our track over speak to itself and say this has 2525
developed many innovations such as FOS, FAS infused which are now used worldwide 2526
to help ensure patient safety. 2527
2528
I would like to comment specifically on one recommendation that we opposed and this is 2529
under the labeling, 7B4. The suggestion reads that establishing and maintaining proximal 2530
control of blood vessels prior to stapling is essential. We disagree. In many procedure 2531
such as splenectomy, colectomy, gastrectomy, and hepatectomy, this would actually 2532
increase risk to your patients. This should not be listed as a labeling indication. 2533
2534
For the remainder of my recommendations, we do -- we do support reclassification of 2535
Class II. We request that you maintain innovation and foster patient safety, which 2536
includes continued access to surgical staplers. We continue to be a patient advocate at 2537
SAGES and it's important for us to put our patients first, they put their trust in us. Thank 2538
you again for your time and consideration on this manner. 2539
2540
LEWIS: Thank you. Dr. Michael Seger, BMI of Texas. 2541
2542
SEGER: Thank you, Dr. Lewis and to the entire committee for the opportunity to speak 2543
today. My name is Michael Seger and my relevant disclosures are, I have done legal 2544
review for surgical device companies. And my travel today up from Texas was paid for 2545
by Medtronic. 2546
2547
58
Getting to know me, I'm a bariatric surgeon and have been so for 15 years. I have 2548
performed several thousand stapling cases. I'm the immediate past president of our Texas 2549
state chapter of the American Society of Metabolic and Bariatric Surgery. And I'm a 2550
founder of a fellowship training program to teach men only invasive surgeons in bariatric 2551
surgeons at home in San Antonio. 2552
2553
So I've used and trained others to use surgical staplers extensively, estimating firing over 2554
30,000 and supervising much more. I've also had these staplers used on myself. I am a 2555
colon cancer survivor and almost exactly four years ago to the date I was undergoing a 2556
laparoscopic extended right colectomy for what turned out to be a stage one cancer. 2557
Thank God. And I'm here today to share with you my perspective on both being a user 2558
and a person who's had this devices used to improve my life. 2559
2560
So, I feel very strongly that these staplers afford us the opportunity to play a critical role 2561
caring for our patients today. And you know when you've heard from others that without 2562
this, we wouldn't be able to do much of the minimally invasive surgical procedures that 2563
we can do. 2564
2565
I heard one of the other FDA physicians mentioned earlier today that it might be more 2566
difficult to see or judge an anastomosis when a minimally invasive approach is used and I 2567
would disagree. I think quite to the contrary, we can see better every single B formation. 2568
2569
When I'm teaching my fellows, we look at each individual stapler. And you guys have 2570
seen how -- those of you who are surgeon, how small those staplers are. It's very difficult 2571
to see in an open procedure the actual formation of every B. So I think the visualization 2572
component is better. 2573
2574
And these benefits also translate to better opportunity cost for our patients getting out of 2575
the hospital with shorter incisions, less pain, quicker return to work. There's no doubt 2576
that it's a wonderful for them. And in truth, it's amazing that I was able to have over half 2577
my colon out with four tiny focal incisions and a little small inch and a half to remove 2578
that specimen. 2579
2580
But as good as they are, these devices require expert surgeon understanding of how they 2581
work and a knowledge of the tissue that we're dealing this as you heard today. So tissue 2582
thickness, staple height choice depends on what we're doing. And in my world, indeed, 2583
every stomach is not created equal, so we make individual determinations. 2584
2585
I would also argue that given also training and experience, you can ask your team the 2586
correct or close to the tissue thickness and choose to staple twice wisely even without 2587
putting your hands on it. 2588
2589
The correct operation of the device is also important when we talk about surgeon use 2590
today. But there are some nuances that also involve the hospital staff. Some even of you 2591
59
know we're receiving these instruments pass to us in the dark, having them prepared in 2592
the back table by attack. 2593
2594
And it's our hope and confidence that they have been trained how to use that and operate 2595
that correctly in order to load it correctly, remove the protected covering in a correct way 2596
and that the stapler was not disturbed before it was handed to us. So it's more than just 2597
surgeon and device company that they are involved in this. 2598
2599
Of course, the tissue must be stabled. You have to avoid punching the tissue in the back 2600
of the stapler. There are many little nuances and things that can be trained and learned. 2601
But at the end of the day, we must check our worked. And it is incumbent upon us as the 2602
surgeon to make sure that this happens. 2603
2604
And quite frankly, I think what's happened overtime is that surgeons may have got a little 2605
complacent. Because these devices are so reliable, we may not be as worried or ready to 2606
check every single B form because they do fire us so reliably. And I've seen this on 2607
surgical videos, people kind of hurrying along just expecting that they're going to work 2608
every time. And I think that this is something less important to notice. 2609
2610
This is our opportunity to make a difference if we have a staple that's off or just a little bit 2611
deviated, we can put a stature, intervene at that time. So at the end of the case, it’s 2612
incumbent upon the surgeon to make sure that everything is as good as it can be. And to 2613
me, these things are a lot higher yield than perhaps doing some bench research on a 2614
product that's been out for five to 10 years. I think we can make a lot of impact in the 2615
training department and to learning department. 2616
2617
But my friends, even when everything goes right as you've heard, we can still have 2618
problems. Most surgeries are being done due to an illness or some condition that's not 2619
normal health. And because of these things that we put together don't always stay 2620
together like we hope that they would. And this not necessarily the fault of the surgeon 2621
or the tool, but rather this is the nature of surgery itself. And it's that thing that keeps us 2622
up worrying all night, those of you know what I'm talking about. 2623
2624
So ladies and gentlemen in the committee, I cannot do what I do for people without this 2625
technology. And I'm not alone in this position. As you heard, multiple different 2626
specialties are using these and it's an essential tool. 2627
2628
Complications, they scare us all and we need to objectively evaluate them routinely as 2629
part of this collaborative effort. And I enjoy being apart to this and listening to this today 2630
because surgery is a team sport and I'm glad to have all of you on the team. These 2631
complications are undoubtedly multi-factorial. Surgeons, hospitals, staffs and industry, 2632
all share equal responsibility along with oversight from this committee and the FDA to 2633
make sure that we push towards the lowest possible rate of adverse events. But thank 2634
you again for the opportunity for being with you today and share my perspective. 2635
2636
60
LEWIS: We have one further speaker who is registered late, Madris. Madris Tomes, 2637
CEO of Device Events. Would you please bring the microphone down so that's close to 2638
you? Thank you. 2639
2640
TOMES: My name is Madris Tomes. Thank you for having me here today. I previously 2641
work for the FDA on both the UDI projects which would be unique device identifier. 2642
And I worked on the MAUDE database which is the Adverse Event Reporting System. I 2643
have no financial interest in the meeting today. I just wanted to come and share what I 2644
know. 2645
2646
The only adverse event reports that are available to the FDA or to the public right now or 2647
through the MAUDE, which is the Adverse Event Reporting System, that can be seen by 2648
the public. 2649
2650
Through April 2019, there have been 135,000 adverse event reports for staples and 2651
staplers. 28,000 of those were injuries and 997 patients died. Those numbers are going 2652
to look a little different from what you saw earlier and I'll explain why. 2653
2654
I wanted to mention that because there was a recent recall. I went and looked out those 2655
adverse events to see the percentage. So the two Ethicon staplers that we recalled in 2656
April, only 4 percent of those adverse events relate to the models that we're discussing 2657
today. So, there are still many problematic staplers on the market. 2658
2659
So the first two device names that you can see on the list here are the two that were 2660
reported this morning. So you can see 72,000 for the implantable staples and then the 2661
staplers that were 23,000 adverse events. I wanted to point out that 25,000 adverse event 2662
reports for staplers and staples were submitted by physicians. 2663
2664
The reason that you see additional device names is because I did a search on staple and 2665
stapler. I wanted to see if we really looking at the full number of issues that are coming 2666
in. And here you can see that there are also staplers used for -- with laparoscope, and 2667
with the DaVinci, and also with mesh. And in fact, I found the large number of staple 2668
issues which was done reported in Kaiser Health News. 2669
2670
I found those because I was looking at mesh reports and found that a lot of a migration 2671
reports were also mentioning staples. So, there's been a lot of discussion today about up 2672
classing the device, and so that's not something that I feel I need to address. But I want to 2673
address is the use of the materials that are in the staples because they are planted into the 2674
body. 2675
2676
So, often in materials that are in staples are nickel, and woman typically know if they're 2677
allergic to nickel because of earrings. And it's actually pretty high percentage of people 2678
that would know that. And if you don't know that you're getting a staple during the 2679
procedure, how would you know to ask whether it's made up of material that you're 2680
allergic too or have a sensitivity to? 2681
61
2682
There's been an announcement that there's going to be a biocompatibility meeting this 2683
fall. The two days have not yet been announced. But the FDA announced it I believe 2684
prior to Dr. Gottlieb leaving. I would like to urge that staples be added to the agenda to 2685
discuss that day. Because right now the device is better going to be discussed at least so 2686
far that have been mentioned would be devices made with nitinoL, Essure, breast 2687
implants, and metal on metal implants for hips. 2688
2689
I did want to point out that the summary reports that were mentioned today have not yet 2690
been made available. They -- when the statement originally came out, it was at the end of 2691
March. And it's now the end of May. And so, we're looking at, it's now going on two 2692
months. Because I worked at FDA, I do remember what this reports look like and how 2693
dirty the data is. So, I'd like to urge the FDA to keep moving on it but I do understand 2694
possibly light is not there yet. 2695
2696
One of the other things that was mentioned is that summary reports are going to be made 2697
public. But I wanted to point out that there was a copy all to that, and that there are 2698
devices that are being litigated right now and those summary reports are being held from 2699
the public. So it essentially what today is pending, if there's a pending litigation, there's 2700
an exemption provided to those companies. I do know that one of those companies had 2701
the device names up there for the robotic surgery. And so where we saw 400 adverse 2702
events, there could be thousands and thousands more. 2703
2704
I'd like to urge that the FDA recommend that the UDI contain any materials that are in 2705
the device and that those are disclosed to a patient, and perhaps even have testing for a 2706
patient prior to anything being implanted in the body. Not all sensitivities and allergies 2707
can be detected in advance, but these will help physicians determine whether sutures or 2708
different types of procedures should be considered. Thank you for your time today. 2709
2710
LEWIS: Thank you. Could all of the -- or action for that, are there any other members of 2711
the audience who wish to speak? I'm seeing none. Would the presenters please assemble 2712
before the podium? And we will have questions from the panel for any of the members 2713
who have presented. 2714
2715
I would like to begin with the question for Dr. Pryor. In your slides, you indicated you 2716
were opposed to the reclassification because it will require PMA. But that's incorrect 2717
based on what's being proposed PMA, but that's incorrect based on what's being 2718
proposed. PMA is with Class III, could you clarify that? 2719
2720
PRYOR: Yes, that's correct. Sorry, the slides were the older slides and that was looking 2721
at Class III. So, for Class II we support it and we don't need to worry about that. 2722
2723
LEWIS: So, let me be clear. So, are you supportive of Class II? 2724
2725
PRYOR: We are supportive of Class II. 2726
62
2727
LEWIS: So, that's contrary to what you stated in your presentation? 2728
2729
PRYOR: My oral statement was absolutely correct. The slides were the old slides, I 2730
apologize. 2731
2732
LEWIS: Good, thanks for the classification. Questions from the panel members? Dr. 2733
Miller? 2734
2735
MILLER: Mike Miller here. I have a question for Dr. Pryor also. I'm curious that you 2736
opposed the recommendation that you get proximal control on vessel before you use a 2737
stapler on them. You know, I don't do this type of surgery very much but that seemed to 2738
violate everything I've ever been taught, you know, so? 2739
2740
PRYOR: So, I think -- yes, if you focus on vascular surgery, proximal and distal control 2741
is what you talk about. If you look at doing a liver resection whether a large vessel is in 2742
it, you actually don't dissect the (INAUDIBLE) use a stapler as your tool. If you're doing 2743
a splenectomy, it's actually safe as if you don't dissect through the pancreatic 2744
(INAUDIBLE) splenic artery. It's safer to fire that stapler alongside the hilum of the 2745
spleen. 2746
2747
So those are some of the ways that we use a stapler and I worry that if the labeling said 2748
you had to have proximal and distal control in some of these cases that would actually be 2749
an off label use that we would do frequently. 2750
2751
MILLER: Right. Would you think it to be a good idea if the language said get practical 2752
or something? I mean, is seems like a general principle to get proximal control for you to 2753
divide the vessel. If the vessel is easily obtained -- if that's easily obtained would it be 2754
reasonable to recommend that you do that before you use a stapler or? 2755
2756
PRYOR: I would hesitant or hesitate to suggest though a labeling indication that says if 2757
practical. It's just I think labeling should be more of a black and white indication and I 2758
think that the vascular control is not. 2759
2760
MILLER: Thank you. 2761
2762
LEWIS: Are there any questions? 2763
2764
UNKNOWN: Again one for Dr. Pryor. With ages be in a court with training surgeons 2765
on how to use staplers and perhaps certifications some indication that they really know 2766
how to do it? 2767
2768
PRYOR: Absolutely, I think that's something we'd support, we do a lot of training in our 2769
meetings and outside, we do online training. I think there's different ways you can do 2770
that and it will be easy to do that sort of a process. 2771
63
2772
UNKNOWN: But what I'm saying is that if they're going to use it, that you have some 2773
degree of certification? 2774
2775
PRYOR: I think it's hard to do that in retrospect with the large number of surgeons that 2776
are in practice today. I think if you came out with the recommendation that said 2777
tomorrow you can't do this unless you have the certification, we'd have problem. 2778
2779
If you could come up with something moving forward just like we do with FLS or FES 2780
that graduating residents have to completed these sets of process, I think that's 2781
reasonable. I think if you wanted to mandate some new training when there's a 2782
modification on the stapler and have sign off on that, I think that's reasonable too. 2783
2784
LEWIS: Other questions, Dr. Miller? 2785
2786
MILLER: Yes, Mike Miller here. I have a question for our last presenter if I could. Are 2787
you aware of any adverse reactions in patients who have a nickel sensitivity from 2788
something like staple? I mean, has that occurred or is that theoretic concern? 2789
2790
PRYOR: It's not theoretical, it definitely has occurred and in fact I was brought that 2791
number and I could look it up for you an answer later. But there are quite a few reports 2792
several hundred with nickel allergies being sided. 2793
2794
MILLER: What kind of complication that these patients have who have a nickel allergy 2795
and they get a staple or a hemoclip put inside their body that has systemic issues or, I'm 2796
just curious. 2797
2798
PRYOR: It causes an autoimmune response. And so, what I typically look for are issues 2799
where you can see local tissue reaction, if there has to be re-surgery or I can look for 2800
symptoms that weren't there previously which would be autoimmune symptoms. 2801
2802
MILLER: Thank you. 2803
2804
LEWIS: May I ask the representatives from Medtronic if you could cast any light on this 2805
issue of material in the staples? I recognize you only responding for your own company 2806
and there they're others might be different. But could you tell us, could we clarify a bit 2807
about what materials are actually included in the staples? 2808
2809
UNKNOWN: Sure. I appreciate the previous speaker bringing this issue. I think it's 2810
something that all those physicians are sensitive too about patient allergies. The majority 2811
of our staples as I understand it had research this prior to coming today are made of 2812
titanium. I don't know if there's any trace elements of nickel so, I can't respond to that. 2813
2814
64
What I can say is that this is not something that we found as an issue with the risk post-2815
market surveillance work. Nor have we seen this of a particular area publish in literature 2816
of it, I could be missing a paper but I haven't seen it. 2817
2818
LEWIS: Thank you. 2819
2820
UNKNOWN: Thank you. 2821
2822
LEWIS: I'm seeing no other questions. I want to thank all of the public speakers for 2823
their presentations. And we will now close the public session portion of this meeting. 2824
Thank you. 2825
2826
The remainder of the afternoon will be spent in answering the questions post by the FDA. 2827
There are five fairly detailed questions. Dr. Dale Rimmer will present this sequentially to 2828
us. Before we start, do any of the panelists have questions of the FDA regarding any of 2829
their presentations this morning that they would like to ask before we proceed? 2830
2831
Seeing none, Dr. Rimmer, would you present the questions? 2832
2833
RIMMER: In the April proposed reclassification order, FDA has identified the following 2834
risk to help for surgical staplers for internal use based on FDA's literature review on 2835
MDR analysis. Complication associated with device failure and malfunction. Devise 2836
failures are malfunctions may result in prolong surgical procedures on plan surgical 2837
interventions and other complications such as bleeding, sepsis, fistula formation, tearing 2838
of internal tissues and organs, increase risk cancer reoccurrence and death. 2839
2840
Complications associated with user error, improper device selection and use. Error may 2841
result from a device design that is difficult to operate and/or labeling that is difficult to 2842
comprehend. For example, user difficulty firing the stapler may result the staplers not 2843
being fully deployed and misfiring may result in staplers being inadvertently applied to 2844
the wrong tissue. An adequate instruction for use may result in selection in correctly size 2845
staples for the target tissue. 2846
2847
When staplers are applied to the wrong tissue or when incorrectly size staplers are 2848
applied. Staplers are unable to properly approximate underlying tissue resulting in tissue 2849
damage, anastomotic leakage and bleeding. This in turn may lead to more severe 2850
complications such as abscess, sepsis, peritonitis, hemorrhage or death. 2851
2852
Adverse tissue reaction if a patient contacting materials of the device or not 2853
biocompatible, local tissue irritation, sensitization, cytotoxicity or systemic toxicity may 2854
occur when the device contacts internal (ph) tissue. Infection, if device is not adequately 2855
reprocess or sterilized, the device may introduce pathogenic organisms and 2856
(INAUDIBLE) tissue and may cause infection to patient. 2857
2858
65
Please comment on whether you believe FDA has identified a complete and accurate list 2859
of the risk to health presented by surgical staplers for internal use. Since the publication 2860
of the proves (ph) for reclassification order in April, FDA has identified the potential for 2861
additional risk specifically associated with power in surgical staplers for internal use. 2862
2863
Please include the consideration of the risk posed (ph) by power surgical staplers in your 2864
comment. 2865
2866
LEWIS: Question … 2867
2868
KRAUS: Yes. So before we start, I just want to remind the panel that the topic is 2869
staplers not staples. We understand staples can, you know, cause certain problems but 2870
regarding biocompatibility but staples are already Class II. We look at those things when 2871
we review staples. So, staplers is the issue and the formation of the staple when it gets 2872
implanted, so the topic of allergies to the staples are really not something we need to 2873
discuss at this panel meeting. Just a reminder. 2874
2875
LEWIS: Doctor Kraus, based on what you just said it would appear then that discussion 2876
that including as a risk of tissue compatibility is should not be included here because 2877
staples are the only report that remain in the body and be at risk for tissue compatibility 2878
presumed by the brief contact between the jaws of the stapler and tissue would not be an 2879
issue? 2880
2881
KLAUS: So, you can -- if there's anything that you think the stapler might leave any 2882
residuals behind that can cause a problem, then that is worth discussing. If not then, you 2883
don't need to discuss it. 2884
2885
LEWIS: And let's address that question since it's very specific. Does anyone feel that 2886
tissue compatibility is an issue for the stapler per se say not the staples? Since that's the 2887
question before us. If not then adverse risk of tissue compatibility could be eliminated 2888
from the list of risk to be considered. Seeing none, there seems to be agreement on that 2889
point. 2890
2891
KLAUS: All right, thank you. 2892
2893
LEWIS: So, let's turn to the questions here which is basically to ask if the panel believes 2894
that the FDA has correctly identified the principle risk associated with the staplers that 2895
need to be address by the reclassification. Dr. Bloom? 2896
2897
LEWIS: Dr. Bloom? 2898
2899
BLOOM: I had noted on my paper before coming to the meeting. I have to agree with 2900
one of the comments made by, I believed the team from Medtronic that I wouldn't 2901
include increased risk of cancer recurrence as part of the conversation for surgical staple 2902
device failure. I don't see it's important in the literature view that I did. 2903
66
2904
LEWIS: Mr. Posner, one of the things that came up in the discussion from Medtronic is 2905
multiple uses of stapler device and that is, how many times can it be reused and for what 2906
topics it can be reused. And I think that's something that needs to be put in there and 2907
assessed. 2908
2909
POSNER: I guess that's relative recommendations but I would certainly agree with you 2910
that the powered staplers which are reusable pose a different risk from the single-used 2911
staplers which can obviously be sterilized in package before going out. So that would… 2912
2913
UNKNOWN: (INAUDIBLE). 2914
2915
POSNER: Yes. Yeah. I think we agree. 2916
2917
LEWIS: Does anyone else feel there are any risks which have been not included that 2918
should be or if there are any risks that are included that should not be among the things 2919
that the FDA has presented. 2920
2921
Yes, Dr. Miller? 2922
2923
MILLER: Could I just hear someone from FDA discuss why they included increased risk 2924
of cancer recurrence in this list? 2925
2926
GIBEILY: Again, George Gibeily, a medical officer. It's what -- it's not good science, 2927
it's not level one evidence but there's a lot of retrospective data and meta-analysis 2928
showing that there is an increased risk of local -- when you get a leak, and I'm not going 2929
to attribute directly to stapler, it could be multifactorial like we've been talking about all 2930
this time. But, leaks supposedly increase the risk of -- I heard Dr. Steve Wexner even 2931
recently talked about the risk -- increased risk of cancer recurrence, this anastomotic 2932
leaks in patients that have cancer. So, I think it's an issue to think about. I'm not going 2933
to, you know, swear my life against it but I think it's an issue to think about as we go 2934
forward. 2935
2936
MILLER: Do you think there is natural human temptation in the part of the surgeon to 2937
compromise their margin because if they go too far they won't be able to put the stapler 2938
on? 2939
2940
GIBEILY: Right. Yeah. And I think that's part of the multifactorial. Certainly, there's a 2941
human element here. There could be damage to the bowel outside the stapler line that 2942
resulted in contamination of the (INAUDIBLE) than we've seen this earlier in our 2943
laparoscopic experience with surgical staplers when we're doing our first colon resections 2944
with more rudimentary instruments where we're damaging the colon and converting 2945
Dukes. Back on those days, we used Dukes classification into more advanced cancers 2946
because cancer cells wherein the (INAUDIBLE) and see the ports, et cetera. 2947
2948
67
So, certainly, there are lots of other potential reasons and I would go with the anal's (ph) 2949
recommendation regarding the inclusion of cancer risk in their list of risks here. 2950
2951
LEWIS: It would seem to me that the cancer recurrence risk would relate principally to 2952
other sites of cancer that are distant from the resection being done or to compromise 2953
margin generally due to failure to recognize for the extension as rather than to any faction 2954
of the stapler itself as a point. 2955
2956
So, speaking in support what Dr. Bloom and Miller say, it seems like unacceptable point 2957
to include. And secondly, trying to think of any method to research that given the time 2958
needed for recurrence to become evident and the lack of any real data regarding staplers 2959
that it's essential and impossible task to investigate. And as a result that (INAUDIBLE) 2960
point I'm trying to include it. 2961
2962
UNKNOWN: Agree. Thank you (INAUDIBLE). 2963
2964
LEWIS: Let me ask the panel. Does anyone disagree with that point that we've raised 2965
that cancer recurrence risk is not a reasonable thing to include? Does anyone disagree 2966
with that? Seeing that, I think we would do that. Where there any other comments 2967
regarding this question? 2968
2969
And Dr. Kraus, it appears to me that the panel is in agreement that the risks you have 2970
identified are appropriate that the issue of increased cancer risk is not something which 2971
would be included as a realistic consideration. And that since we are dealing only with 2972
staplers and not staples that the biocompatibility risk is also something that could be 2973
eliminated. 2974
2975
KRAUS: Does that answer your question inadequately? 2976
2977
LEWIS: So, you're saying then that the third bullet regarding adverse tissue reaction to 2978
the staples should be not considered? However, biocompatibility of the device even 2979
though it does barely touches the patient, we should still assess the simple 2980
biocompatibility that would be normally assessed for the device contact with the patient. 2981
2982
KRAUS: Well, I think the general feeling is that biocompatibility of the device given 2983
that's very short term exposure would really not be an issue. 2984
2985
LEWIS: All right, thank you for your comment. Dr. Rimmer (ph), could we go to 2986
question two? 2987
2988
RIMMER (?): As defined at 21 CFR 860.7(d)(1), there is reasonable assurance that a 2989
device is safe when it can be determined, based upon valid scientific evidence, that the 2990
probable benefits to health from use of the device for its intended uses and conditions of 2991
use, when accompanied by adequate directions and warnings against unsafe use, 2992
outweigh any probable risks. The valid scientific evidence used to determine the safety of 2993
68
a device shall adequately demonstrate the absence of unreliable risk in illness or injury in 2994
association with the use of the device for its intended uses and conditions of use. 2995
2996
As defined in 21 CFR 860.7(e)(1), there is reasonable assurance that a device is effective 2997
when it can be determined, based upon valid scientific evidence, that in a significant 2998
proportion of the target population, the use of the device for its intended uses and 2999
conditions of use, when accompanied by adequate directions for use and warnings against 3000
unsafe use, will provide clinically significant results. 3001
3002
Please comment on whether based upon the available scientific evidence there is a 3003
reasonable assurance of safety and effectiveness for surgical staplers for internal use. 3004
3005
LEWIS: So the question as I understand at all, that doesn't state explicitly you're asking 3006
is whether there is a reasonable assurance of safety and effectiveness for surgical staplers 3007
based on the current classification of staplers as Category 1 not 2. Is that correct? 3008
3009
Dr. Kraus, do you want to clarify that? 3010
3011
KRAUS: Yeah. So, I think basically what the question they're asking is in order to -- for 3012
you to feel that there is a reasonable assurance that a device is effective when it can be 3013
determined, you know, that's available can that be done if the device is Class I or can you 3014
do it if the device is Class II? 3015
3016
LEWIS: Which we seemed to heard in essentially unanimous opinion from multiple 3017
people that under Class II, it's inadequate that the answer to the question would be no. 3018
And so whether the answer to the question of whether Class II would be adequate, I 3019
would ask for any expression of opinion around the table as to whether people feel that or 3020
whether in fact they feel that Class III would be necessary to go to more stringent 3021
controls. 3022
3023
Dr. Pories? 3024
3025
PORIES: I'm happy with Class II but I think we need better information such as a 3026
registry. When we say valid scientific evidence, we don't really have much evidence of 3027
what's actually happening out there. So registry I think would be a big help. 3028
3029
KRAUS: So, valid scientific evidence as defined by the FDA is what's available in the 3030
literature. Of course, you know, clinical studies, case reports, there's many forms of valid 3031
scientific evidence. Animal studies can be considered, you know, ade -- you know, valid 3032
scientific evidence, so I think in that sense, the FDA would certainly be happy with any 3033
recommendation that has to do with registries. We do encourage registries, and if that's 3034
something the panel would like to recommend that there'll be -- you know, that the FDA 3035
try to, you know, access a registry where such information could be provided, we would 3036
be happy to look into it. 3037
3038
69
At this point, I'm not sure that that registry exists but if it does, we -- you know, we're 3039
happy to try to, you know, use registry data. So, that's a recommendation you can make. 3040
We're happy to do that. 3041
3042
LEWIS: Dr. Posner? 3043
3044
POSNER: So personally, I'd point out you can't have staplers without staples, and you 3045
can't have staples without staplers. But all of the adverse events we've seen are the basis 3046
of both of them and we don't know which one was at fault. When it was reported, and I 3047
think in the reporting for this would be very important to know whether if the stapling 3048
failed, was it because the stapler was the wrong stapler to be used or was it because the 3049
powder of the stapler that was used to put it in place which caused it to fail. 3050
3051
And so I think if you're talking about registry, you're talking about records, once you 3052
make the staplers a Class II just like the staples are, it would be really important to know 3053
what the failure was with the surgeon, the gun or the stapler itself. 3054
3055
And I don't know if you can get that in your report. But I think for scientific analysis that 3056
would be really important, there's default. 3057
3058
LEWIS: Dr. Meurer. 3059
3060
MEURER: So, I guess, I would be I guess a little worried about how we would interpret 3061
the results of a registry and that if we have this registry, how would we -- how would we 3062
learn about the patient factors. These are very sick patients with very bad diseases, if you 3063
would have to try to do open sewing for anastomoses for example versus using a device. 3064
People die when they have open sewing procedures. Specific comparison group is a little 3065
challenging. 3066
3067
It doesn't sound like a bad idea but I don't know if our question is do we enough right 3068
now to say whether there's a reasonable assurance of the safety and effectiveness of 3069
surgical staplers. 3070
3071
I think from what's been presented and from some of the public comments from surgeons 3072
who use this frequently, I think there is reasonable assurance of the safety and 3073
effectiveness consistent with the Class II designation and special controls as DFA is 3074
proposing. 3075
3076
Maybe I'll learn more through other methods but I think we have to consider what we 3077
might learn from those types of registries given that it's such a individualized patient 3078
surgeon decision as to how to approach a problem within individual patient. 3079
3080
LEWIS: Dr. Pories. 3081
3082
70
PORIES: You know, when we started to do research with therapeutic surgeon, it made a 3083
big difference of who was doing what and who supplied the materials. And I think if you 3084
found that manufacturer A had made fewer of these problems than manufacturer B, I 3085
think it should be a great help. It's very easy to have a registry who use this. We had no 3086
problems, or if you did have problems. 3087
3088
LEWIS: Dr. Meurer. 3089
3090
MEURER: It's easy to have a registry. It's hard to have people put data into it. There's a 3091
cost to that. Surgeries are very dynamic thing who's going to (INAUDIBLE) the 3092
surgeons. We're already going nuts of what we to do in the electron health record to 3093
begin with. 3094
3095
I guess everything comes with a cost. And I know we're not supposed to talk about costs 3096
here. But my concern would be that the registry would be subject too much of the 3097
underreporting that we see here and that we might not get those great answers. I believe 3098
in an ideal world where we have the resources to collect data in a way that we could all 3099
rely on. That could be very beneficial to see early signals of problem with this specific 3100
type of device. But, it does -- you know, resources are required and effort and time that 3101
surgeons could be operating on their next patient. 3102
3103
PORIES: I agree totally there's a cost. But at the end of this case the circulating nurse 3104
enters what is done. And I think that if it's-- since (INAUDIBLE) electronic medical 3105
records, I don't think the cost would be high. The cost is there, absolutely. 3106
3107
LEWIS: I'd like -- yes? I'm sorry. Dr. Miller. 3108
3109
MILLER: Thank you. Mike Miller here. I fully agree with my colleague here, Dr. 3110
Meurer, on this issue. I think these have been used thousands and thousands times. And 3111
we don't have perfect data or even maybe high quality data on problems that occur, but it 3112
appears to be quite low in terms of how -- and the benefit of using this device is so 3113
enormous. The risks are always going to be there to some agree. You can't ever remove 3114
those completely. I think the risk benefit ratio is strongly in favor of using the devices. 3115
You can improve them. 3116
3117
I think if you try to create a registry and try to tease out where the surgeon role and the 3118
(INAUDIBLE) device was, you try to find zero surgeon role because nobody report that 3119
if there was an outpatient, you know. 3120
3121
So, I think the meaning (ph) on this data would be difficult to really understand. I think a 3122
Class II device with special control is probably very adequate for this and I'm very 3123
comfortable with that. 3124
3125
LEWIS: So, I would like to ask the panel then for consensus opinion around us. Please 3126
comment the specific question. Please comment on whether based on the available 3127
71
scientific evidence, there's no reasonable assurance of safety and effectiveness or surgical 3128
statements for internal use as a Class II device. Does anyone disagree with that on the 3129
panel? 3130
3131
So, seeing none. Dr. Kraus. The panel feels that Class II classification would provide 3132
reasonable assurance of safety and effectiveness. Regarding the question of a registry, 3133
there's a divergence of opinion on the panel and there's no unanimous opinion about the 3134
use of that. There are some dissenting voices regarding the difficulties of implementing 3135
registry, I think they've given the extremely low incidence of adverse reactions. 3136
3137
And so, there's no uniform recommendation from that, no consensus opinion and the 3138
DFA would need to evaluate further the technicality of doing that. 3139
3140
UNKNOWN: Thank you. Appreciate the response. 3141
3142
LEWIS: Dr. Meurer proceed question three. 3143
3144
MEURER: In the April proposed reclassification order, FDA proposed that the following 3145
special controls would adequately mitigate the risks to health and provide reasonable 3146
assurance of safety and effectiveness for surgical staplers for internal use. 3147
3148
Performance testing must demonstrate that the staples when used with compatible staples, 3149
performs as intended under anticipated conditions of use. 3150
3151
Performance testing must include the following, evaluation of staple formation 3152
characteristics in the maximum and minimum tissue thickness for each tissue type, 3153
measurement of the worst-case deployment pressures on stapler firing force, 3154
measurement of staple line strength, confirmation of staple line integrity and in vivo 3155
conformations of staple hemostasis. 3156
3157
Usability testing and labeling comprehension studies must demonstrate that the clinician 3158
can correctly select and use the device as identified in the labeling based on reading the 3159
directions for use. 3160
3161
Elements of the device may contact the patient and must be demonstrated to be 3162
biocompatible. 3163
3164
Performance data must demonstrate the sterility of the device. 3165
3166
Validation of cleaning and sterilization instructions must demonstrate that any reusable 3167
device components can be safely and effectively reprocessed according to the 3168
recommended cleaning and sterilization protocol in the labeling. 3169
3170
Performance data must support the shelf life of the device by demonstrating continued 3171
device functionality, sterility and packaging integrity over the identified shelf life 3172
72
3173
Labeling of the device must include the following. Unless data demonstrates the safety 3174
of doing so, contraindications must be identified regarding the use of the device on 3175
tissues for which the risk of stapling outweighs any reasonably foreseeable benefit due to 3176
unknown complications including the stapling of necrotic or ischemic tissues and tissues 3177
outside of the labeled limits of tissue thickness. 3178
3179
Unless available information indicates that the specific warnings do not apply, the 3180
labeling must provide adequate warnings regarding how to avoid know hazards 3181
associated with device use including avoidance of obstructions to the creation of the 3182
staple line and the unintended stapling of other anatomic structures, avoidance of 3183
clamping and unclamping of delicate tissue structures to prevent tissue damage, 3184
avoidance of use of the stapler on large blood vessel such as the aorta. 3185
3186
Establishing and maintaining proximal control of blood vessels prior to stapling. 3187
3188
Approximate -- appropriate measures to take if a stapler malfunction occurs while 3189
applying staples across a blood vessels such as clamping or ligating the vessel before 3190
releasing the stapler, while the stapler is still closed on the tissue, and ensuring stapler 3191
compatibility with staples. 3192
3193
Specific user instructions for proper device use including measures associated with the 3194
prevention of device malfunction, evaluation of the appropriateness of the target tissue 3195
for stapling, and evaluation of the resultant staple line. 3196
3197
List of staples with which the stapler has been demonstrated to be compatible. 3198
Identification of key performance parameters and technical characteristics of the stapler 3199
and the compatible staples needed for safe use of the device. Information regarding 3200
tissues on which the stapler is intended be used. Identification of safety mechanisms of 3201
the stapler. Validated methods and instructions for reprocessing of any reusable device 3202
components. An expiration date/shelf life. 3203
3204
Package labels must include critical information and technical characteristics necessary 3205
for proper device selection. 3206
3207
Please comment on whether you believe any other special controls are necessary to 3208
mitigate the risk to health and provide a reasonable assurance of device safety and 3209
effectiveness or whether you disagree with the inclusion of the special controls. Also, 3210
please comment on whether if you believe that needs special controls maybe necessary 3211
for powered surgical staplers such as electrical safety, (INAUDIBLE), compatibility 3212
testing and software validation and verification. 3213
3214
LEWIS: So, this is a very extensive list of special controls which has been listed and we 3215
are being asked if these are appropriate, if some of them should be eliminated or if others 3216
should be added. 3217
73
3218
I would begin outset (ph) by saying that one of the element which is listed here states the 3219
elements of the device that may contact the patient must be demonstrated to be 3220
biocompatible. In essence, we've already discussed and eliminated that. So that should 3221
be deleted from your list. 3222
3223
Number two, usability testing and a labeling comprehension study must demonstrate that 3224
the clinician can correctly select and use the device as identified in the labeling based on 3225
reading the directions for use. 3226
3227
I don't know how that could practically be carried out. Dr. Kraus could you perhaps 3228
elaborate on what you were thinking in including that and how you would possibly (ph) 3229
done, otherwise it would appear that that's a very difficult thing to do. It's basically 3230
testing and reading comprehension of surgeons. 3231
3232
KRAUS: So, I think that is a strong suggestion that individuals look at the labeling. 3233
However, you're free to recommend that we remove that if you think that's appropriate. 3234
3235
LEWIS: Yes, Dr. Meurer? 3236
3237
MEURER: I mean, it seems like a sponsor could potentially meet this by showing it to 3238
five surgeons who are -- like the directions to five surgeons who are in a panel with them 3239
or advisors to make sure that what is shown there is intuitive on the instructions we used. 3240
I know that a lot of times people have learned over the years how the devices work. 3241
3242
I think there was some testimony earlier of people talking about it would be nicer if there 3243
were ways to make sure people could learn to use the devices correctly, you know like -- 3244
but it, again, you can't guard against other, you know, sort of misuse. 3245
3246
But it seems like it is possible to learn if the human factors associated with the 3247
instructions were used are at least understandable to the intended users. And I don't 3248
know if that's necessarily an honor as part of the labeling. 3249
3250
KRAUS: So let me just say that, that is really basically -- if you're talking about the 3251
bullet point usability testing, is that what you're talking about? 3252
3253
MEURER: Well, I was really thinking more about the -- when it speaks about a labeling 3254
comprehension study, that seems… 3255
3256
KRAUS: Right. 3257
3258
MILLER: … a little different than usability testing. 3259
3260
KRAUS: Right. So that's kind of both. There is -- when we provide -- when a company 3261
provides labeling, one of the ways to assess whether or not the labeling is useful is that 3262
74
you -- there is critical tasks that need to be performed when using any medical device. 3263
And we have individuals at FDA who know how to design or assess studies that look at 3264
that information. 3265
3266
So, the company will prepare directions for use. The study would include say, 15 3267
surgeons, they would be asked to look at the labeling, read the labeling. And then be able 3268
to use the device appropriately and do, you know, the critical tasks that have been 3269
identified. 3270
3271
And if they can do it and everything works out fine, then we feel like the labeling is 3272
appropriate. If they have problems, you know -- and, you know -- I mean, I can't -- I'm 3273
not a surgeon so for me to tell you what those critical tasks would be -- is really not 3274
appropriate. But, if let's say someone can't, using the directions assess the appropriate 3275
staple for the appropriate tissue, then we would assume there is some problem with the 3276
way the labeling is written. 3277
3278
And so then, we would go back to the company and say, since this problem showed up, 3279
we think you need to rewrite that section. And then the company would rewrite that 3280
section and then they would do the testing again. 3281
3282
And once that's been done and you can go through the testing and show that those 3283
individuals can actually understand and everything works appropriately and the critical 3284
tasks are performed, then we would say that the labeling is appropriate and that, you 3285
know, we think that it can be cleared. So I think that's what that's getting at. 3286
3287
LEWIS: I think based on what you say that the -- we would generally be supportive of 3288
that. We heard earlier today that there's always a conflict between identifying all possible 3289
risks and problems versus having such an intensive reading list (ph) and no one pays 3290
attention to it. So, you obviously make balance between that. 3291
3292
I don't think there's an issue when we talk about the adequacy of the labeling. The 3293
problem comes up when you get into the question of reading comprehension which 3294
implies the evaluation of the reader. That seems to me to be very difficult. So as long as 3295
the focus is on the labeling, and on people's ability to understand to utilize it, then there's 3296
probably no objection. 3297
3298
KRAUS: OK. So we will make sure that we write that in that way. 3299
3300
LEWIS: Thank you. And then I ask the panel about all the other -- this is a very 3301
extensive list, we've heard from Dr. Rimmer that there is a concern specifically about 3302
powered staplers regarding their risks specifically identified this potential power factors, 3303
electromagnetic factors. I assume all of these are battery-powered as opposed to 3304
plugging into the wall. Is that correct? 3305
3306
UNKNOWN: The ones that I'm aware of are battery-powered. 3307
75
3308
LEWIS: Speak up, I can’t (ph). 3309
3310
UNKNOWN: The ones that I am aware of are all battery-powered. 3311
3312
LEWIS: Is that true? OK. So, the sterility (ph) issue that's already been discussed seems 3313
to me to be a specific problem because the non-sterile devices are packaged to then some 3314
sort of an enclosure and doing that in the operating room always poses risk in handling. 3315
They're not present with a totally sterile device since you open for one-time use. That 3316
would seem to be an issue as I think we've already discussed that needs to be included in 3317
the special controls. 3318
3319
Are there other issues that the panel wishes to identify either adding special controls not 3320
included or deleting special controls listed here? 3321
3322
Yeah, Dr. Posner. 3323
3324
POSNER: I'd look at the second box on 34 and it says, avoidance of clamping and 3325
unclamping of delicate tissue structures to prevent tissue damage, and that just triggered 3326
something that Medtronic said that some of the damage to their staplers has occurred 3327
overtime by inappropriate clamping of the stapler. And so, you might have to include 3328
something like that of inappropriate clamping of the stapler, and I would let Medtronic 3329
come up with the appropriate wording. 3330
3331
On the previous one, I agree about the training wording and I think you need to have the 3332
lawyers go through that and say what a reasonable surgeon would then be able to 3333
interpret as far as the things go, and, you know, let the legal guys do it. Because that 3334
could be a medical-legal issue somewhere down the road. 3335
3336
LEWIS: There is -- it is included in the sense in the bullet point. It says, specific user 3337
instructions for proper device use including measures associated with the prevention of 3338
device malfunction, evaluation of the appropriateness of the target tissue for stapling 3339
which identifies the issue you've just raised. So it is included there. 3340
3341
Dr. Bloom? 3342
3343
BLOOM: Matthew Bloom. Prior to the meeting, it struck me as oddly the indication to 3344
the -- the control rather to get possible blood vessel control prior to applying staples. It's 3345
not common surgical practice in many tissue types that the staples are used. And in fact, 3346
it would not allow you to take some tissues close to the organs as possible. 3347
3348
The minimization of dissection can be advantageous to the patient as opposed to really 3349
clarifying the blood vessels are getting controlled prior to following -- firing the staples 3350
themselves or the proximal distant control when ideally have properly fired the knife 3351
should be safe. Which leads to the follow-up point that perhaps the statement that the 3352
76
surgeons should be aware if there -- should be -- should have a backup plan anytime 3353
going over a named vessel that something doesn't well to quickly get blood vessel 3354
control. 3355
3356
But to make it a statement I think should be removed. 3357
3358
LEWIS: So you're speaking to the fact that establishing and maintaining a proximal 3359
control of blood vessels prior to stapling should be eliminated? 3360
3361
BLOOM: Yes sir. 3362
3363
KRAUS: So, you can recommend that we eliminate that or you can recommend that we 3364
work with companies, any appropriate societies to reword that. What -- whichever you 3365
would like to recommend would be fine. 3366
3367
BLOOM: I'm not against rewording it, it strikes me, however, that should be removed. 3368
3369
LEWIS: Does anyone disagree that it should be removed? Seeing none... 3370
3371
BLOOM: Well, it makes me uncomfortable but I don't do this, so -- and this is just -- I've 3372
always been my habit to control that vessel before I cut it. So if these things are such that 3373
you don't need to do that anymore, and 99.999 percent of cases, I'm good with that, you 3374
know. But I defer to your judgment on that and I certainly won't disagree with that. 3375
3376
But it does make me a little uncomfortable not to have possible (INAUDIBLE). You can 3377
get it especially if the vessels are sitting -- if the link to the vessel sitting there and you 3378
just can lope (ph) it or something just to be prepared in case the thing fails. I would take 3379
a moment to do that if I could, you know. 3380
3381
So -- but how to put that -- I'll let -- 3382
3383
LEWIS: In a sense, the closure of the (INAUDIBLE) before stapling does that. So for 3384
the proximal control not really seem to be necessary. 3385
3386
Dr. Meurer? 3387
3388
MEURER: Seems like to me there might be -- this is Will Meurer. We might be trying 3389
to add labeling indications for good surgical practice. I mean, the other one about, you 3390
know, don't use this thing on the aorta. I mean, don't use it on the left ventricle, you 3391
know, don't use it on the -- you know, like the trachea. Like -- I mean, I guess where 3392
does that ends? 3393
3394
So, I think there are really good points where it may not be that that's for the patients to 3395
actually get the proximal control of the splenectomy example that was previously cited. 3396
So, it may be OK that -- it maybe better to delete some things that are trending towards 3397
77
good surgical practice but very contextual to the actual situation of the type of surgery if 3398
we can. I think it would be -- we could ask them to work with agencies but I think for 3399
some of those things like don't use it this way, it may be within the realms of logical 3400
surgical practice. 3401
3402
So that's, you know -- so it maybe that -- you know, I certainly be in favor of just 3403
eliminating it, potentially eliminating the thing about don't staple the aorta because like 3404
what exactly is a large blood vessel. There's nothing larger than the aorta but -- so I 3405
would favor of eliminating that too. 3406
3407
LEWIS: Ms. Pawelski? 3408
3409
PAWELSKI: Well, similar to that question, I'm not sure what FDA intended when they 3410
talked about information regarding tissues on which the staplers intended to be used. 3411
Isn't that a physician decision? 3412
3413
LEWIS: Is that -- where do you see that? 3414
3415
PAWELSKI: It's the fourth from the bottom of the bullets between identification of 3416
safety mechanisms and identification of key performance parameters. 3417
3418
LEWIS: So you're saying information regarding tissues on which the staplers intended to 3419
be used, is that it? 3420
3421
PAWELSKI: I'm not sure what FDA meant by that. And my question is, is that -- isn't 3422
that a physician decision on which tissue to use it on? 3423
3424
LEWIS: Dr. Kraus, do you want to respond? 3425
3426
KRAUS: I think -- I'd like to let Dr. Gibeily comment. 3427
3428
GIBEILY: George Gibeily. Dr. Lewis, I -- you know, when a -- lot of our labeling is 3429
recommended based on adverse events in marketplace, i.e. stapling across the aorta, some 3430
(ph) really bad happened when someone did that. And it self-evident-- I mean, it's self -- 3431
people realize that you don't staple across big blood vessels like the aorta. 3432
3433
Regarding proximal control, that was my suggestion and I have done a number of 3434
laparoscopic splenectomies for example, and I agree with our sagacious (ph) president 3435
that you don't necessarily want to sect (ph) out each and every blood vessel because you 3436
can get in trouble. No doubt, you’re going to get pancreatic phospholipase (ph), you can 3437
get bleeding, et cetera. 3438
3439
However, we not intriguingly would decide (ph) to have the splenic artery for example to 3440
decrease the blood supply in case we did get in trouble within an escape vessel as we 3441
were going across the splenic pedicle. So I think the idea of proximal in the liver for 3442
78
example knowing where the (INAUDIBLE) so you can do a Pringle maneuver if you got 3443
into bleeding as you're going across it with a stapler. I think that counts as proximal 3444
control for me. 3445
3446
So, that was the spirit of putting that in there. I am not sure what the other question was. 3447
I'm sorry. 3448
3449
PAWELSKI: What did you mean by information regarding tissues on which the staplers 3450
intended to be sued? 3451
3452
GIBEILY: Well, I mean, there may be some tissues that are very delicate such as the -- 3453
you know, a vein, a type of hepatic vein for example where you want to use the right 3454
staple for that tissue because if you don't you're going to tear the tissue and get into 3455
horrendous bleeding. I'm trying to think of other examples, maybe some of the biliary 3456
strictures, maybe too delicate for a stapler to go across without causing significant 3457
collateral injury to the stric -- to the biliary tree in that area. 3458
3459
I think that was what we are intending on that. 3460
3461
LEWIS: Does that answer your question? 3462
3463
PAWELSKI: Yeah. It was similar to the question isn't that the -- I mean, is that 3464
practical, doctors basically know that. I think the caution is, you know, how much does 3465
the label talk about the practice of medicine and dictate how well a surgeon does versus 3466
allowing them to make those decisions. So, that's the spirit of question. 3467
3468
LEWIS: Panel member number 70 in response specifically to that. 3469
3470
UNKNOWN: Doctor, is that a question? 3471
3472
LEWIS: No, but do you want to respond to that (INAUDIBLE). 3473
3474
UNKNOWN: Well, I think (INAUDIBLE) the right patient. First of all, are we dictating 3475
what acceptable type of surgical technique is probably beyond the (INAUDIBLE). And 3476
maybe we could go back where Frankie (ph) put in the concept of being aware or be 3477
prepared. You know, if the (INAUDIBLE) if the staple -- if control is not (INAUDIBLE) 3478
stable vessel, surgeons should be prepared, you know, to have seems more -- gives more 3479
leeway without telling exactly how to do it possible disorder. It might be prepared to 3480
have, that'll be a real warning (INAUDIBLE). And if you come across a vessel that you 3481
take it and it doesn't control it. Surgeon must be prepared and take appropriate action. 3482
3483
(OFF-MIC) 3484
3485
79
GIBEILY: I might add that many of those languages -- George Gibeily. Many of those 3486
labeling and suggestions are already being put in the labeled by the major stapling 3487
company. So, I'll just add that to it. 3488
3489
UNKNOWN: So, when we put together this, we thought it's better to include more than 3490
less because we wanted this discussion and we're happy to hear your opinions and we're 3491
happy, you know, for you to tell us what you think is overkill and what is -- you know, 3492
where -- if anything is missing. So, don't fell like, you know, you're making us feel bad 3493
by telling us, you know, what you think needs to come out. 3494
3495
Also, you can suggest ways that we could get proper wording or, you know, you can 3496
suggest that we, you know, have a, you know, weakness, SAGES and Medtronic and 3497
whatever to sit down together to come up with what would be appropriate labeling, that 3498
could be a suggestion. 3499
3500
We don't, you know, we want to hear what you really think and, you know, like I said 3501
when we put this together, you know, we said, well, should we put this in and should we 3502
put that. We just thought, well, let's just put it all in and let the panel tell us what, you 3503
know, we need to take out or what we need to modify. So, this is good. This is kind of 3504
conversation we hope that we would hear. 3505
3506
LEWIS: Yes? 3507
3508
UNKWOWN: You know, there's-- as long you asking, there's actually a big problem in 3509
industry with several companies making that that the color codes indicate the thickness of 3510
the staple except the color codes vary by company. 3511
3512
So, for example, the Covidien vascular stapler with tight staples as gold, the Ethicon 3513
white. And that's standardization is key because it's not just the surgeon. It's the 3514
circulator opening up a staple. And they will hand you the wrong staple because you 3515
think they opened up a Covidien but they opened Ethicon. And it's-- it can lead to 3516
disaster if you're stapling across the vessel with, you know, four millimeter staples. So, 3517
that could be great standardization industry that all vascular staplers are, you know, 3518
certain thickness but they all have to be one color. 3519
3520
I think that's a big factor. It causes a lot of -- if, you know, I pay attention of that and it 3521
causes me to throw away a lot of staplers because the wrong stapler was opened. 3522
3523
LEWIS: Sounds like an actual suggestion. So, the additional point that's not included 3524
here would be to the FDA to seek uniformity in the color coding of staplers manufactured 3525
by different companies so that there's uniformity in that classification. Dr. Miller. 3526
3527
MILLER: Mike Miller here. I think that first circle bullet point there on labeling, I think 3528
you can make a stronger statement on that and just say you should not use the stapler on 3529
80
necrotic or ischemic tissue, any tissue you want to heal. I wouldn't staple it because they 3530
will not heal. 3531
3532
And if it's necrotic or ischemic or if it's neoplastic surgeon, I would add that to the list. I 3533
wouldn't staple across the tumor because it's not going to heal either and the chance of 3534
failure is high if you're stapling across dead ischemic or neoplastic tissues. So… 3535
3536
LEWIS. Dr. Miller, that's a pretty basic surgical (ph). 3537
3538
MILLER: It is. But, it's in here. So, I don't know. Should we just eliminate that totally 3539
or -- it's a piece of the labeling here. Do we need to say that or … 3540
3541
LEWIS: I would think if you have to read that label. You need to go back to residency, 3542
OK. Dr. Levy? 3543
3544
LEVY: And I'd like some clarification on what is worst-case deployment pressures and 3545
how that specifically translates into something that the surgeon would need to be 3546
cognizant of -- on a daily basis. That's under performance testing by the way. 3547
3548
LEWIS: I haven't found that yet. Oh, I see. Performance testing must include 3549
measurement of the worst-case deployment pressures on stapler firing force. Correct? 3550
Dr. Muerer, you want to address that? 3551
3552
MEURER: So, thanks for your question. That is regarding the forces for manual staplers 3553
that you have to exert to deploy that staple. 3554
3555
UNKNOWN: So, it's the minimum pressure that's required. 3556
3557
MEURER: The minimum and the maximum pressure, too much pressure if it's requiring 3558
a lot of pressure can lead to twerking of the instrument if it's, you know, in an extreme 3559
value. And then also -- also the minimum value is also important too so that the stapler’s 3560
not inadvertently fired. 3561
3562
KRAUS: Thanks for that clarification. 3563
3564
LEWIS: Dr. Pories? 3565
3566
(OFF-MIC) 3567
3568
PORIES: My suggestion would be is that this is just too detailed and when you're 3569
(INAUDIBLE) nobody is going to read it. And perhaps the FDA could be encouraged to 3570
work with safeties (ph), leadership intention (ph) and thoracic society (INAUDIBLE) to 3571
develop simple, clearly defined labels, perhaps with some illustrations. 3572
3573
81
HICKS: Hicks, I just want to make sure we'll get down this road. You’re right on to, I 3574
think, alter, you know, to write them (ph). We're trying here trying to write the thing now 3575
versus, you know, having some input from different groups. It's the way to kind of look 3576
at. 3577
3578
But, you know, we want to -- the ultimate goal is to have safety for the patient but also in 3579
fairness to the surgeon, the way it's written for medical legal reasons I think is important. 3580
Obviously companies think about that when you write them for yourselves. 3581
3582
But, in reality, let's say all the stuff is put on there, it would be overwhelming, it might 3583
put the physician in unfair situation, you know, even if he did the right thing but didn't 3584
work. And then they came back say, look, the 27 says this, if 52 says that. So I just -- I 3585
like your idea that I think bringing back and try to picture simple main stuff to meet. 3586
3587
LEWIS: Seeing no other comments. Then I would summarize Dr. Kraus, the panel feels 3588
that the item regarding usability testing needs to be rewarded to focus specifically on text 3589
of the instructions and their usability as opposed to anything regarding that 3590
comprehension of the reader. 3591
3592
Second, that the one that states the elements, it must contact, the patient must be 3593
demonstrated to be biocompatible be eliminated that the bullet point establishing and 3594
maintaining proximal control of blood vessels prior to stapling needs to be rewarding -- 3595
rewarded to imply that it's an element of practice and needs to identify some differences 3596
in vessels and recognize if there's an issue as opposed to given the explicit instructions 3597
that an additional point be added regarding attempting to color code uniformity among 3598
the different manufactures for the depth to the staples. 3599
3600
And, overall, that the list perhaps should be reduced in size and that it'll be tested against 3601
the existing organizations such as SAGES in terms of the use of this by those who do a 3602
great deal of surgery requiring stapling. 3603
3604
That seems to be the consensus of the group. 3605
3606
KRAUS: So, thank you for the excellent discussion. And -- oh, go ahead. 3607
3608
UNKNOWN: One quick question. In the SAGES technology would seem like -- maybe 3609
some people are getting better by seeing DVD or some do better by reading. If the DVD, 3610
good quality DVD was put together, they could show as, you know, as well instead of 3611
just reading and you should talk about tissue and all the problems that you're talking 3612
about. So, this is how -- this bad, don't do this, do this. So, if you like you look at the 3613
DVD, I think it would be better way at least for learning. 3614
3615
I think (INAUDIBLE) are in that -- you know, their lives will be like, they like to see as 3616
well as just to read about other textbook. 3617
3618
82
UNKNOWN: Right. So, many companies do put labeling online and they could make 3619
videos. We don't have a problem with that, so. 3620
3621
LEWIS: Dr. Meurer proceed question number four. 3622
3623
MEURER: Section 513 of the Food, Drug and Cosmetic Act states that a device should 3624
be Class III if insufficient information exists to determine that general controls are 3625
sufficient to provide reasonable assurance of its safety and effectiveness or that 3626
application special controls would provide such assurance and that addition -- if in 3627
addition, the device is life supporting or life sustaining or if a use which is of substantial 3628
importance in preventing impairment of human health, or if the device presents a 3629
potential unreasonable risk of illness or injury. 3630
3631
The device should be Class II if general controls by themselves are insufficient to provide 3632
reasonable assurance of the safety and effectiveness, and if sufficient information to 3633
establish special controls to provide safety assurance. 3634
3635
The device should be Class I if, general controls are sufficient to provide reasonable 3636
assurance of the safety and effectiveness, or insufficient information exist to determine 3637
that general controls are sufficient to provide reasonable assurance of the safety and 3638
effectiveness, or establish special control provides safety assurance. 3639
3640
But, is not reported or represented to be for use and supporting or sustaining human life 3641
or for a use which is substantial importance in preventing impairment of human health 3642
and does not present any potential and reasonable risk of illness or injury. 3643
3644
Please comment on whether the general controls required for or all medical devices are 3645
insufficient to provide a reasonable assurance of safety and effectiveness for surgical 3646
safety for internal use. 3647
3648
LEWIS: This question seems to be redundant to discussion we've already had. I mean, if 3649
we have pretty thorough discussion about the fact that Class I is an adequate, Class II is 3650
adequate and Class III is not necessary. I'm not sure what additional you want us to 3651
address. Dr. Kraus, can you clarify that? 3652
3653
KRAUS: So, I think this could be more for the record. So, I think, you know, you can 3654
say that in response to, A, you can ask the question of the panel whether or not you 3655
believe that whether the panel agrees or disagrees that general controls are insufficient. 3656
For B, you can ask the panel whether they agree or disagree with the fact that general 3657
controls and special controls are sufficient, and C, that -- so, let me read C before I say 3658
something. 3659
3660
Yeah, so, that as far as C goes that you either believe or do not believe that surgical 3661
staplers present a unreasonable risk of illness or injury. OK. And if you can answer 3662
those three questions for the record so that it's stated publicly then you can go on. 3663
83
3664
LEWIS: OK. Let's present that to the panel. Do any panelists wish to discuss those 3665
three -- any of those three issues before we ask for consensus opinion? 3666
3667
All right. Let's go to question A. Please comment on whether general controls are 3668
insufficient to provide a reasonable assurance of safety. So, we're asking to confirm that 3669
Class I is inadequate basically. Does anyone disagree with that statement? So, we have 3670
(INAUDIBLE) that? 3671
3672
KLAUS: So, you are recommending Class I is insufficient? 3673
3674
LEWIS: Correct. 3675
3676
KLAUS: Thank you. 3677
3678
LEWIS: B, please comment on whether you agree or disagree that the application of 3679
general controls plus special controls are sufficient to provide assurance -- reasonable 3680
assurance of safety and effectiveness for surgical staplers for internal use, et cetera. 3681
3682
Basically, stating that the conditions of Class II are adequate for managing this, the 3683
alternative view is that we would need to go to Class III. Does anyone disagree with that 3684
statement? 3685
3686
If not, then seems to be unanimous opinion of Class II with general and special controls 3687
are adequate for the regulation staplers. 3688
3689
KRAUS: Thank you. 3690
3691
LEWIS: C, FDA places the staplers for internal use or for use which is a substantial 3692
important in preventing impairment to human health but does not present a potential 3693
unreasonable risk of illness or injury when intended to deliver comparable staplers to 3694
internal tissues or whatever surgical purpose. 3695
3696
So, basically, stating that we feel that the overall use staplers under Class II requirements 3697
would be appropriate present unreasonable risk. Does anyone disagree with that 3698
statement? Seeing none. There's unanimity of opinion that that's also correct. 3699
3700
KRAUS: So, you're telling me they shouldn't be Class III. Is that correct? 3701
3702
LEWIS: That's right. 3703
3704
KRAUS: Thank you. 3705
3706
LEWIS: Turn to question five. 3707
3708
84
MEURER: Based upon the available scientific evidence and special controls presenting 3709
question three. Do you recommend Class I general controls, Class II special controls or 3710
surgical staplers for internal use when used for -- use when intended to deliver 3711
compatible staplers to internal tissues during surgical resection, transactional (ph) 3712
creating an osteomiosis. Please provide a rationale for your final classification 3713
recommendation taking the account, the available scientific evidence in your response to 3714
question four above. 3715
3716
LEWIS: That would seem to be a recapitulation about what we just said. 3717
3718
KRAUS: I agree. So, again, for the record -- for the record for number five, you are 3719
recommending Class II. 3720
3721
LEWIS: Is there any disagreement on the Panel if that's inappropriate? Good. Then, I 3722
think we're done with the questions. 3723
3724
KRAUS: Thank you. 3725
3726
LEWIS: All right. I believe that finishes our job for the day. Do any panel members 3727
including the special representatives for industry consumers, et cetera, have any special 3728
comments to add about any issue here that we discussed today? Dr. Posner? 3729
3730
POSNER: I'd say this went really smoothly and it's nice to see the entire panel agreeing 3731
on everything along with the industry and everybody else and finishing an hour and a half 3732
early. 3733
3734
LEWIS: Thank you. Then I think -- Commander Garcia, do you have any final 3735
comments? 3736
3737
GARCIA: No, sir. Thank you. 3738
3739
LEWIS: Then we will stand adjourn for the day and we will reassemble tomorrow 3740
morning at 8:00, not 9:00, as we did today. And we will then address hemostatic devices. 3741
3742
Thank you very much, all, for your excellent work today. I appreciate everything you've 3743
done. 3744