reuse of single use devices cdrh/cber mdufma stakeholder meeting presented by: barbara zimmerman

Reuse of Single Use DevicesReuse of Single Use Devices

CDRH/CBER MDUFMA CDRH/CBER MDUFMA Stakeholder MeetingStakeholder Meeting

Presented by: Barbara Zimmerman

Sec. 302 – Single-Use Medical Sec. 302 – Single-Use Medical Devices (SUDs)Devices (SUDs)

Certain reprocessed SUDs identified by Certain reprocessed SUDs identified by FDA must include validation data.FDA must include validation data.

Validation data includes cleaning, Validation data includes cleaning, sterilization, and functional performance sterilization, and functional performance data demonstrating substantial data demonstrating substantial equivalence.equivalence.

Requirements of Sec. 302Requirements of Sec. 302

For reprocessed SUDs which are exempt from For reprocessed SUDs which are exempt from 510(k) requirements, determine which “critical” 510(k) requirements, determine which “critical” reprocessed SUDs are no longer exemptreprocessed SUDs are no longer exemptFederal Register notice- dated April 30, 2003 Federal Register notice- dated April 30, 2003 (List I)(List I)Federal Register notice- dated June 26, 2003 Federal Register notice- dated June 26, 2003 (added non-electric biopsy forceps to List I)(added non-electric biopsy forceps to List I)

Due date for validation data to be submitted to Due date for validation data to be submitted to FDA – July 30 and Sept. 26, 2004FDA – July 30 and Sept. 26, 2004


Determine which non-exempt reprocessed Determine which non-exempt reprocessed SUDs require validation dataSUDs require validation data

Federal Register notice- dated April 30, Federal Register notice- dated April 30, 2003 (List II)2003 (List II)

Due date for validation data to be Due date for validation data to be submitted to FDA – January 30, 2004submitted to FDA – January 30, 2004


For reprocessed SUDs which are exempt For reprocessed SUDs which are exempt from 510(k) requirements, determine from 510(k) requirements, determine which “semi-critical” reprocessed SUDs which “semi-critical” reprocessed SUDs are no longer exemptare no longer exempt

Federal Register notice- dated April 24, Federal Register notice- dated April 24, 2004 (List I)2004 (List I)

Due date for 510(k)s with validation data Due date for 510(k)s with validation data to be submitted to FDA – July 24, 2005to be submitted to FDA – July 24, 2005

Comments Submitted to DocketComments Submitted to Docket

Bundling of reprocessed SUDsBundling of reprocessed SUDs

Review Prioritization SchemeReview Prioritization Scheme

Update of Lists I and II to include Update of Lists I and II to include additional devicesadditional devices

Timeliness of FDAs review of validation Timeliness of FDAs review of validation datadata

SUPPLEMENTAL VALIDATION SUPPLEMENTAL VALIDATION SUBMISSIONSSUBMISSIONS

for Reprocessed Single-Use for Reprocessed Single-Use Medical Devices (SUDs)Medical Devices (SUDs)

Ginette Y. Michaud, MDGinette Y. Michaud, MDOffice of Device EvaluationOffice of Device Evaluation

November 18, 2004November 18, 2004Gaithersburg , MarylandGaithersburg , Maryland

Supplemental Validation Submissions Supplemental Validation Submissions (SVSs)(SVSs)

July 2003: guidance on the validation data July 2003: guidance on the validation data to be submittedto be submitted

June of 2004, updated guidance with June of 2004, updated guidance with information on review timelines.information on review timelines.

Supplemental Validation SubmissionsSupplemental Validation Submissions

53 SVSs anticipated accounting for 1800 device 53 SVSs anticipated accounting for 1800 device modelsmodels

9 SVSs were not submitted – all NSE9 SVSs were not submitted – all NSE

44 SVSs received;44 SVSs received;19 SE19 SE12 SE for some models12 SE for some models11 NSE or withdrawn11 NSE or withdrawn2 under review2 under review


CDRH accounted for 1800 device modelsCDRH accounted for 1800 device models52% found SE - may continue to be legally 52% found SE - may continue to be legally marketed marketed 33% found NSE (no data or inadequate 33% found NSE (no data or inadequate data submitted) data submitted) 15% withdrawn by the reprocessor. 15% withdrawn by the reprocessor.


Reprocessed SUDs that were withdrawn Reprocessed SUDs that were withdrawn or found NSE may no longer be legally or found NSE may no longer be legally marketed.marketed.

Reprocessors of these SUDs may submit Reprocessors of these SUDs may submit new 510(k) premarket notifications to FDA.new 510(k) premarket notifications to FDA.


In completing MDUFMA mandate, CDRH:In completing MDUFMA mandate, CDRH:

– accounted for 1800 SUD models accounted for 1800 SUD models

– addressed complex scientific issuesaddressed complex scientific issues

– resource intensive and interactive resource intensive and interactive processprocess

– careful and thorough reviewscareful and thorough reviews

– timely and scientifically grounded timely and scientifically grounded regulatory decisions regulatory decisions

How can users access information on How can users access information on the status of their reprocessed SUDs?the status of their reprocessed SUDs?

Users can determine which models are Users can determine which models are legally marketed and which ones are not.legally marketed and which ones are not.

The status of previously cleared The status of previously cleared reprocessed SUDs appears on FDA’s reprocessed SUDs appears on FDA’s Reuse website, at: (Reuse website, at: (http://www.fda.gov/cdrh/reusehttp://www.fda.gov/cdrh/reuse//))

REPROCESSING OF REPROCESSING OF SINGLE USE DEVICESSINGLE USE DEVICES

(SUDS)(SUDS)

MDUFMA Stakeholder’s Meeting MDUFMA Stakeholder’s Meeting November 18, 2004November 18, 2004

Steven Turtil, M.S.Steven Turtil, M.S.FDA/CDRH/ODE/DAGID/INCBFDA/CDRH/ODE/DAGID/INCB

510(k) Data – Reprocessed SUDs510(k) Data – Reprocessed SUDs

With each application, data should be submitted With each application, data should be submitted and reviewed for:and reviewed for:

Cleaning Validation Cleaning Validation

Sterilization ValidationSterilization Validation

Functionality TestingFunctionality Testing

– No StandardsNo Standards

– No StandardsNo Standards

– Standards AvailableStandards Available

– Guidance and Standards AvailableGuidance and Standards Available

How do we want to define “Clean”How do we want to define “Clean”

To allow for successful, subsequent To allow for successful, subsequent sterilization steps.sterilization steps.

To limit to a minimum, the organic soil To limit to a minimum, the organic soil transfer from one patient to another.transfer from one patient to another.

To prevent accumulation of residual soil To prevent accumulation of residual soil (and to prevent the development of (and to prevent the development of biofilms) after multiple cycles.biofilms) after multiple cycles.

FDA Recommended Validation Data, Post-Simulated Use, for Cleaning of SUDs

Body Contact

Device ExamplesBlood Path Ophthalmic Tissue Compromised Skin

EP Catheters Phacoemulsification Tips

Biopsy Forceps, Arthroscopes,

Fixation Devices

Vascular Compression Devices (external)

TESTTYPES

Test soil to be selected and

justified according to the intended use of

the device

Visual Inspection

Total Protein

Hemoglobin

Carbohydrates

Contrast Media(where appropriate)

No Visible Soil No Visible Soil No Visible Soil No Visible Soil

Table of ContentsTable of Contents

Cleaning Process:Cleaning Process: Instructions for technicians - highly variable between reprocessors.Instructions for technicians - highly variable between reprocessors.Cleaning Process:Cleaning Process: Instructions for technicians - highly variable between reprocessors.Instructions for technicians - highly variable between reprocessors.

Cleaning Process Validation:Cleaning Process Validation: What is it?What is it?Cleaning Process Validation:Cleaning Process Validation: What is it?What is it?

– Artificial Soils and Simulated Use Protocols:Artificial Soils and Simulated Use Protocols: How are you going to get the devices dirty?How are you going to get the devices dirty?


– Cleaning Validation Protocols:Cleaning Validation Protocols:How are you going to test the Cleaning Process?How are you going to test the Cleaning Process?


– Test Protocols and Cleaning EndpointsTest Protocols and Cleaning EndpointsAnd a summary of Sterility, Endotoxin and Detergent ResiduesAnd a summary of Sterility, Endotoxin and Detergent Residues


Cleaning ProcessCleaning Process

Cleaning Instructions should specify:Cleaning Instructions should specify:Cleaning Instructions should specify:Cleaning Instructions should specify:

Point-of-Use DecontaminationPoint-of-Use Decontamination

Disassembly, if possibleDisassembly, if possible

Automated or Manual cleaning, or a combination – Automated or Manual cleaning, or a combination – time, temperature, brushing duration, etc.time, temperature, brushing duration, etc.

Ultrasound –Ultrasound –time, temperature, setting (high, medium, low) time, temperature, setting (high, medium, low)

Detergents, Enzyme Detergents – Detergents, Enzyme Detergents – time, temp., concentration, cycle limit (replenishing) time, temp., concentration, cycle limit (replenishing)

Intermediate Rinse Steps – Intermediate Rinse Steps – time, temp., particular water quality specifications.time, temp., particular water quality specifications.


Cleaning Process:Cleaning Process: Instructions - highly variable between reprocessors.Instructions - highly variable between reprocessors.Cleaning Process:Cleaning Process: Instructions - highly variable between reprocessors.Instructions - highly variable between reprocessors.

Cleaning Process Validation:Cleaning Process Validation: What is it?What is it?

Cleaning Process Validation:Cleaning Process Validation: What is it?What is it?








Cleaning Process:Cleaning Process: Instructions - highly variable between reprocessors.Instructions - highly variable between reprocessors.Cleaning Process:Cleaning Process: Instructions - highly variable between reprocessors.Instructions - highly variable between reprocessors.

Cleaning Process Validation:Cleaning Process Validation: What is it?What is it?Cleaning Process Validation:Cleaning Process Validation: What is it?What is it?







Cleaning Process ValidationCleaning Process Validation

Use of actual clinical contamination as well as simulated Use of actual clinical contamination as well as simulated organic organic soil thatsoil that represents intended clinical exposurerepresents intended clinical exposure..

Simulation of worst case clinical use conditions: Simulation of worst case clinical use conditions: – Inoculation sites should be Inoculation sites should be most difficult to cleanmost difficult to clean– DurationDuration of exposure should mimic worst case of exposure should mimic worst case– ArticulationsArticulations/Flextures/Manipulations, etc. /Flextures/Manipulations, etc.

Worst case cleaning conditionsWorst case cleaning conditions..

Use of actual clinical contamination as well as simulated Use of actual clinical contamination as well as simulated organic organic soil thatsoil that represents intended clinical exposurerepresents intended clinical exposure..

Simulation of worst case clinical use conditions: Simulation of worst case clinical use conditions: – Inoculation sites should be Inoculation sites should be most difficult to cleanmost difficult to clean– DurationDuration of exposure should mimic worst case of exposure should mimic worst case– ArticulationsArticulations/Flextures/Manipulations, etc. /Flextures/Manipulations, etc.

Worst case cleaning conditionsWorst case cleaning conditions..

Cleaning Validation Protocols should support and confirm the Cleaning Validation Protocols should support and confirm the effectiveness of the Routine Cleaning Instructions and should include effectiveness of the Routine Cleaning Instructions and should include consideration of:consideration of:

Cleaning Validation Protocols should support and confirm the Cleaning Validation Protocols should support and confirm the effectiveness of the Routine Cleaning Instructions and should include effectiveness of the Routine Cleaning Instructions and should include consideration of:consideration of:

Cleaning Validation ProtocolsCleaning Validation Protocols

Should Include Should Include WORST CASEWORST CASE consideration of: consideration of:Should Include Should Include WORST CASEWORST CASE consideration of: consideration of:

Automated, Manual or a combination – Automated, Manual or a combination – time, temperature, brushing durationtime, temperature, brushing duration


Detergents, Enzyme Detergents – Detergents, Enzyme Detergents – time, temp., concentration, time, temp., concentration, cycle limit (replenishing).cycle limit (replenishing).


Automated, Manual or a combination – Automated, Manual or a combination – time, temperature, brushing durationtime, temperature, brushing duration


Detergents, Enzyme Detergents – Detergents, Enzyme Detergents – time, temp., concentration, time, temp., concentration, cycle limit (replenishing).cycle limit (replenishing).


Cleaning Validation ProtocolsCleaning Validation Protocols Compare Cleaning Instructions with Validation ProtocolsCompare Cleaning Instructions with Validation Protocols

If instructions say “Sonication 20 – 25 min.,” If instructions say “Sonication 20 – 25 min.,” then validation should be for 20 min. or less.then validation should be for 20 min. or less.

Examples (note set-points, tolerances):Examples (note set-points, tolerances):

If instructions say “Not to exceed 12 devices per If instructions say “Not to exceed 12 devices per cleaning load,” then validation should be performed with cleaning load,” then validation should be performed with 12 devices, or more. 12 devices, or more.

Test Protocols and Cleaning EndpointsTest Protocols and Cleaning Endpoints

Specify the endpointsSpecify the endpoints of cleaning, and data of cleaning, and data should meet them – at the end of its use-life.should meet them – at the end of its use-life.

Visual InspectionVisual Inspection should be part of both the should be part of both the routine cleaning and the cleaning validation routine cleaning and the cleaning validation (yet realize the limitations: e.g., (yet realize the limitations: e.g., lumens)lumens)..

Extraction methodExtraction method should be validated. should be validated.

Test methodsTest methods should be validated. should be validated.

Specify the endpointsSpecify the endpoints of cleaning, and data of cleaning, and data should meet them – at the end of its use-life.should meet them – at the end of its use-life.

Visual InspectionVisual Inspection should be part of both the should be part of both the routine cleaning and the cleaning validation routine cleaning and the cleaning validation (yet realize the limitations: e.g., (yet realize the limitations: e.g., lumens)lumens)..

Extraction methodExtraction method should be validated. should be validated.

Test methodsTest methods should be validated. should be validated.

SterilizationSterilization

StandardsStandards are available for validation methods. are available for validation methods. – ISO 11134 – Industrial Moist HeatISO 11134 – Industrial Moist Heat– ISO 11135 – Ethylene Oxide ISO 11135 – Ethylene Oxide

Applicants should provide a “Applicants should provide a “summary of the sterilization process summary of the sterilization process design and validation activitiesdesign and validation activities.” .”

Use of routine methods for evaluation of Use of routine methods for evaluation of endotoxinsendotoxins on medical on medical devices, for those devices required to be labeled as such. Testing devices, for those devices required to be labeled as such. Testing should be conducted on final, sterilized product (as always).should be conducted on final, sterilized product (as always).

StandardsStandards are available for validation methods. are available for validation methods. – ISO 11134 – Industrial Moist HeatISO 11134 – Industrial Moist Heat– ISO 11135 – Ethylene Oxide ISO 11135 – Ethylene Oxide

Applicants should provide a “Applicants should provide a “summary of the sterilization process summary of the sterilization process design and validation activitiesdesign and validation activities.” .”

Use of routine methods for evaluation of Use of routine methods for evaluation of endotoxinsendotoxins on medical on medical devices, for those devices required to be labeled as such. Testing devices, for those devices required to be labeled as such. Testing should be conducted on final, sterilized product (as always).should be conducted on final, sterilized product (as always).

BundlingBundlingReprocessing a group of closely related device models based on validation data for a Reprocessing a group of closely related device models based on validation data for a “representative” worst case model. “representative” worst case model. How was the worst case device selected?How was the worst case device selected?– Were all materials considered?Were all materials considered?– All geometric variances?All geometric variances?– Is there validation data to support this?Is there validation data to support this?– Or a scientifically valid justification?Or a scientifically valid justification?

An especially tricky issue:An especially tricky issue: slight differences in materials may result in different surface slight differences in materials may result in different surface characteristics, and unexpected consequences with regard to cleaning effectiveness. characteristics, and unexpected consequences with regard to cleaning effectiveness. Bundling between different manufacturers’ products should be validated or scientifically Bundling between different manufacturers’ products should be validated or scientifically justified, because device designs can be very dissimilar.justified, because device designs can be very dissimilar.

Reprocessing a group of closely related device models based on validation data for a Reprocessing a group of closely related device models based on validation data for a “representative” worst case model. “representative” worst case model. How was the worst case device selected?How was the worst case device selected?– Were all materials considered?Were all materials considered?– All geometric variances?All geometric variances?– Is there validation data to support this?Is there validation data to support this?– Or a scientifically valid justification?Or a scientifically valid justification?

An especially tricky issue:An especially tricky issue: slight differences in materials may result in different surface slight differences in materials may result in different surface characteristics, and unexpected consequences with regard to cleaning effectiveness. characteristics, and unexpected consequences with regard to cleaning effectiveness. Bundling between different manufacturers’ products should be validated or scientifically Bundling between different manufacturers’ products should be validated or scientifically justified, because device designs can be very dissimilar.justified, because device designs can be very dissimilar.

MDUFMA STAKEHOLDERS MDUFMA STAKEHOLDERS MEETINGMEETING

Reuse of Single Use Devices Reuse of Single Use Devices Panel – Compliance UpdatePanel – Compliance Update

November 18, 2004November 18, 2004

Reprocessor Inspection Update - Reprocessor Inspection Update - HospitalsHospitals

Over 225 inspections conducted since 8/2000Over 225 inspections conducted since 8/2000Three types of Inspections:Three types of Inspections:– Routine surveillance, i.e. f/u to hospital registrationRoutine surveillance, i.e. f/u to hospital registration– ““For Cause” i.e. f/u to informant reportsFor Cause” i.e. f/u to informant reports– Sample of hospitals based on their responses to a Sample of hospitals based on their responses to a

contractor survey contractor survey

Findings: Findings: – Most hospitals were either not reprocessing or Most hospitals were either not reprocessing or

promised to discontinuepromised to discontinue– A few early inspections led to FDA correspondence; A few early inspections led to FDA correspondence;

one Warning Letter and two untitled lettersone Warning Letter and two untitled letters

Reprocessor Inspection Update – Reprocessor Inspection Update – Third Party FirmsThird Party Firms

In the 1990s, there were 15-20 reprocessing In the 1990s, there were 15-20 reprocessing firmsfirmsEarlier inspections commonly found GMP Earlier inspections commonly found GMP problems in validation, purchasing controls & problems in validation, purchasing controls & component controlscomponent controls17 Warning Letters have issued17 Warning Letters have issued2 injunctions were filed; both firms went out of 2 injunctions were filed; both firms went out of businessbusinessAll currently registered firms (5) have been All currently registered firms (5) have been inspected; all recent inspections found in inspected; all recent inspections found in substantial compliancesubstantial compliance

Compliance Follow-up to NSEs and Compliance Follow-up to NSEs and WithdrawalsWithdrawals

Calls made to all applicants (5 firms) to Calls made to all applicants (5 firms) to determine withdrawal plans for distributed determine withdrawal plans for distributed productproductAll applicants have withdrawn/are withdrawing All applicants have withdrawn/are withdrawing productproductInspection assignment developed to verify Inspection assignment developed to verify discontinuance of reprocessingdiscontinuance of reprocessingInspection to cover special concerns raised by Inspection to cover special concerns raised by Office of Device Evaluation, i.e. packagingOffice of Device Evaluation, i.e. packagingInspection assignments request review of Inspection assignments request review of validation for the firm’s key processes validation for the firm’s key processes

reuse of single use devices cdrh/cber mdufma stakeholder meeting presented by: barbara zimmerman

Documents

data reprocessed suds

review slide

nonexempt reprocessed

maryland slide

fdacdrhodedagidincb

reprocessed single

semicritical reprocessed

inadequate data