Global Harmonization Task Force

O

Iava

s and com-ristics ent of 693

practitioners are now subject to federal and state regula-tions regarding the use of these devices and are strongly influenced by international standards and agreements. The arena of medical device standards and regulations is co mplex and arcane, and there is much overlap of authority. This chapter reviews the history, present sta-tus, interested parties, relevant standards, standards processes, and pending developments that will affect the clinician in the future. The reader should be left with a good understanding of both the processes and the inter-ested parties in the constantly evolving international setting of standards and regulations.

the optimum degree of order in a given context.1 Stan-dards should be based on the consolidated results of sci-ence, technology, and experience, and they should be aimed at the promotion of optimum community benefits. In reality, a standard is an agreed restriction for a com-mon good and a shared benefit.1

REGULATION OF MEDICAL DEVICES

The rules governing medical devices differ throughout the world.2 Many different models exist, such as the U.S. Food Medical Device Regulation in the United StatesDefinition of Terms

Medical Device Regulation in the European Union

Medical Device Regulation in JapanMedical Device Regulation in China

ROLE OF STANDARDS IN MEDICAL DEVICE REGULATIONEarly Efforts in the United StatesFood and Drug AdministrationHistoryOrganization of the Food and Drug

AdministrationClassification of DevicesEuropeUnited States

Classifying a Device in the United StatesPremarket and Placing-on-Market Processes

Stages in the Development of International Standards

Organization of Standards Development Organizations

U.S. Standards Development Organizations of InterestAmerican National Standards Institute (ANSI)ASTM InternationalAssociation for the Advancement of Medical

Instrumentation (AAMI)National Fire Protection Association (NFPA)Institute of Electrical and Electronics

Engineers (IEEE)Medical Device StandardsThe General Standard (60601-1)Standards of Particular Interest

Other Standards and ChangesInteroperabilitySmall-Bore ConnectorsAlarm Systems

VERVIEW

t was once possible to practice safe and modern nesthesia without any knowledge of the regulatory and oluntary standards governing anesthesia equipment nd practice. This has changed, however, and individual

What Is a Standard?A standard is a document, established by consensuapproved by a recognized body, that provides formon and repeated use, rules, guidelines, or charactefor activities or their results, aimed at the achievemStandardS

CHAPTER OUTLINE

OVERVIEWWhat Is a Standard?

REGULATION OF MEDICAL DEVICESCHAPTER 3 4

and regulatory ConSiderationS

Michael B. Jaffe David G. Osborn

Pending Regulatory Changes in the United States

MEDICAL DEVICE VOLUNTARY STANDARDSOverview

PART VII Safety, StandardS, and Quality694

and Drug Administration (FDA), European Union (EU) CE-marking system, and various registrations, listings, licenses, and approvals in other countries. Efforts have been under way since the early 1990s via organizations such as the Global Harmonization Task Force (GHTF) to better achieve uniformity among national medical device regulatory systems around the world. This is being done with two aims in mind: enhancing patient safety and increasing access to safe, effective, and clinically beneficial medical technologies.

Global Harmonization Task ForceA partnership between regulatory authorities and regulated industry, the GHTF consisted of five founding members: the European Union, United States, Canada, Australia, and Japan. The GHTF intended to foster international harmo-nization in the regulation of medical devices by the devel-opment of a regulatory model and supporting documents to underpin globally harmonized regulation of medical tech-nologies. Regulatory and industry representatives from Europe, the Asia-Pacific region, and North America were encouraged to collaborate and actively participate in the development of guidance documents that describe regula-tory practices to ensure the safety, effectiveness, and quality of medical devices. This task has been substantially com-pleted, the GHTF has published many final documents on their Web site, and some countries have based their newly developed regulatory processes on these documents. Not-withstanding this success, little progress has been made by the founding members of the GHTF in the harmonization of their regulatory processes to this model. Many other countries, particularly some of the BRIC countriesBrazil, Russia, India, and Chinaunsuccessfully attempted to join the GHTF.

The FDA proposed, and the five founding members agreed, that the time had come to dissolve the GHTF and create a new, regulator-only forum with global reach that would consult with other interested groupsincluding industry, health care professionals, and consumersin the advancement of regulatory harmonization. In October 2011, the regulatory authorities of Australia, Brazil, Can-ada, China, the European Union, Japan, and the United States and the World Health Organization (WHO) announced the establishment of the International Medical Device Regulators Forum (IMDRF) to replace the GHTF. The IMDRF intends to provide guidance on strategies, policies, directions, and activities to accelerate international medical device regulatory harmonization. Unlike the GHTF, various stakeholder groups, such as industry, aca-demia, health care professionals, and consumer and patient groups, are no longer invited to participate in the steering committee or management committee, although they can be invited to participate in ad hoc working groups.

Medical Device Regulation in the United StatesManufacturers of medical devices distributed in the United States must comply with certain basic regulatory requirements: Establishment registration Quality Systems (QS) regulation Labeling requirements Premarket Notification 510(k), unless exempt, or

Premarket Approval (PMA) Medical device listing Medical Device Reporting (MDR)

Definition of Terms

Establishment Registration. A manufacturer must file its name and all places of business with the FDA. Any additional place of business must be registered immedi-ately. Registration is performed electronically.

Quality System Regulation. The QS regulation requires the manufacturer to have a written quality system that is subject to periodic audit by the FDA. The QS regulation requires every medical device to be designed, manufac-tured, packed, stored, and installed in conformity with current Good Manufacturing Practices (GMP). The QS regulation requires use of design validation, investigation of complaints, and a corrective and preventive action plan to identify root causes of product nonconformance with standards and specifications and to implement effective actions to prevent recurrence.

Labeling Requirements. Medical devices must be labeled either on the medical device or on its immediate container. The label must identify the company name, trade name, or trade symbol of the manufacturer as well as the name and place of business of the manufacturer, packager, or distributor and the identity of and quantity of the contents of the package. In addition, the labeling of a medical device must provide adequate directions for use and adequate warnings against unsafe use for a layperson, unless the medical device is a prescription medical device, in which case the labeling may be written for health care professionals. The labeling of a prescription medical device may be made available electronically.

Premarket Notification 510(k). The 510(k) process is designed to ensure, through a quality review process, that marketed medical devices, subject to general and applicable special controls, provide a reasonable assur-ance of safety and effectiveness. It is also designed to foster innovation. This is achieved by comparing the (new) device to an existing (predicate) moderate-risk medical device and demonstrating that the new medical device is substantially equivalent to the predicate. The 510(k) process applies to moderate-risk medical devices (typically class II; Table 34-1).

Premarket Approval. The premarket approval (PMA) process is designed to ensure that a specific marketed medical device provides a reasonable assurance of safety and effectiveness through a scientific review process of safety and effectiveness data (clinical trials). The PMA process applies to novel medical devices or new high-risk medical devices (typically class III; see Table 34-1).

Medical Device Listings. A manufacturer must file a list identifying each medical device made or processed for commercial distribution in the United States and its

reasonably suggests that a medical device has or may have caused or contributed to the death or serious illness of or serious injury to a patient, or when they learn of an event that might contribute to the death or serious illness of or serious injury to a patient should it reoccur.

Medical Device Regulation in the European UnionIn the EU, medical devices are regulated by one of three directives: the Medical Devices Directive (MDD), the Active Implantable Medical Devices Directive (AIMDD), or the In Vitro Diagnostic Directive (IVDD). Directives are an instrument from the European Parliament direct-ing each member state to enact a law that embodies the content of the directive. The directives establish the reg-ulatory scheme based on a risk-based classification system and, for higher risk devices, a certified quality system. The directives establish broad safety and performance criteria called the Essential Requirements (ERs). All medi-cal devices are required to demonstrate compliance with the ERs.

Medical Device Regulation in JapanThe Pharmaceutical Affairs Law (PAL) applies to all med-ical devices in Japan. PAL is controlled by the Ministry of

tern) approval.

Medical Device Regulation in ChinaThe State Food and Drug Administration (SFDA) is the central government agency in charge of drug and medical device administration with functions similar to those of the FDA in the United States. All medical devices must be registered with the SFDA before they are exported to or sold in China. The SFDA process requires in-country testing of medical devices for the Chinese market. Addi-tionally, certain measuring devices require a separate metrological approval.

The General Administration of Quality Supervision, Inspection, and Quarantine (AQSIQ) is tasked with over-sight, inspection, and quarantine as well as with establish-ing the technical standards for imported and exported goods. AQSIQ maintains responsibility for certifying electrical safety for a wide variety of products with the so-called China Compulsory Certificate (CCC). The CCC safety license process requires manufacturers to obtain the CCC mark before exporting or selling prod-ucts listed in the CCC catalog into the Chinese market. The CCC mark is administered by the Certification and Accreditation Administration (CNCA). The China Qual-ity Certification Centre (CQC) is designated by the CNCA to process CCC mark applications. Electrical 3

labels and labeling. Additionally, the manufacturer must provide a notice of discontinuance once a medical device is no longer made. Listing is performed electronically.

Medical Device Reporting. Manufacturers of moderate- and high-risk medical devices (class II or class III) must report to the FDA when they learn of information that

TABLE 34-1 Comparison of FDA 510(k) Premarket N

Factor 510(k) Premarket Notification

Classes of devices Class I and II devicesNumber annually 2428*Documentation (length) Depends on type of submission

(special, traditional)Typically 50 to 250 pages

Regulatory requirement Reasonable assurance of safety

Evidence Substantial equivalence: comexisting predicate medical de

Clinical studies provided? Varies depending on device typ10% with clinical studies

Review period (goal/typical) 90/120 days (traditionally 74%Average time for anesthesiolog

Source of required information

21 CFR 807.87

Outside review? NoUser fees $4717

*2011 actual.An analysis of FDA 510(k) data from 2006 to 2010, Emergo Group (JaThree-year average, fiscal years 2006 to 2008.2012 actual.CFR, Code of Federal Regulations; FDA, Food and Drug Administration4 StandardS and regulatory ConSiderationS 695

Health, Labor, and Welfare (MHLW). All medical devices are classified with a Japanese classification rule that was basically an adopted GHTF rule. Based on the classification, a medical device can require notification, cer-tification, or approval (respectively, from lower to higher risk and from lower to higher effort). Additionally, certain measuring devices require a separate metrological (pat-

otification and Premarket Approval

Premarket Approval

Class III devices24*Typically thousands of pages

and effectiveness Reasonable assurance of safety and effectiveness

parison to an vice

Scientific review process of safety and effectiveness data

e, overall about Required for both safety and effectiveness

of submissions)y branch: 140 days

180/410 days

Section 515(c)(1) of the federal Food, Drug, and Cosmetic Act

FDA Advisory Panel meeting$220,050Additional changes made via PMA supplements

nuary 9, 2012).

; PMA, Premarket Approval.

The U.S. FDA reviews standards and, when found appropriate, recognizes them as suitable by publishing them in the Federal Register (FR). Manufacturers may then use those standards to simplify regulatory submis-sions. The EU harmonizes standards that they find acceptable by publishing them in the Official Journal (OJ). A harmonized standard has a special status. Medical devices that comply with the relevant harmonized stan-dards are presumed to demonstrate compliance with the relevant essential requirements, and this presumption cannot be easily challenged.

Early Efforts in the United StatesThe passage of the Federal Food, Drug, and Cosmetic Act (FD&C Act) of 1938 was hastened by a tragedy the previous year in which nearly a hundred people died after ingesting Elixir Sulfanilamide.3 This act included new provisions to: Extend control to cosmetics and therapeutic medi-

cal devices Start a new system of drug regulation that requires

new drugs to be shown to be safe Loosen misbranding requirements by eliminating

the need to prove intent to defraud Ensure that safe limits be created for unavoidable

poisonous substances Authorize food standards created for identity, qual-

ity, and container filling Authorize medical device factory inspections Add the remedy of court injunctions against viola-

tive manufacturersIncreasing public concern over the safety and effec-

tiveness of medical devices in the late 1960s and early 1970s led to the formation of a study group within the Department of Health, Education, and Welfare, the

1993MedWatchlaunched1990

Safe MedicalDevices Act

1976Medical DeviceAmendments

1976FIGURE 34-1 nTimeline of Food and Drug AdministrSince 1976, the FDA and medical device regulation has evolved. A timeline showing significant events since 1976 is shown in Figure 34-1.

Food and Drug AdministrationHistory

The Food and Drug Administration is a scientific, regula-tory, public health agency whose mission is to protect and promote public health. One of its purposes is to establish a reasonable assurance of the safety and effectiveness of medical devices marketed in the United States. Regula-tion of medical devices in the United States by the FDA has been undergoing an evolution since the passage of the Medical Device Amendments in 1976. This evolution (see Fig. 34-1) has included the passage of several pieces of legislation and the establishment of important reporting and disclosure tools, such as MedWatch (www.fda.gov/Safety/MedWatch/ucm170520.htm) and ClinicalTrials.gov.

The meaning of the terms safety and effectiveness is depen-dent on the risk profile of the medical device. For low-risk medical devices (class I), general postmarketing controls are considered sufficient to provide reasonable assurances of safety and effectiveness. For moderate-risk devices (class II) for which there is sufficient information, so-called special controlstypically a combination of standards and guidance documentsare considered sufficient to provide reason-able assurances of safety and effectiveness. For high-risk devices (class III) or for those medical devices on which there is not sufficient information, scientific evidence from well-controlled clinical trials is required to provide reason-able assurances of safety and effectiveness.

Medical Device Amendments of 1976. In 1976, the Med-ical Device Amendments (21 U.S.C. Secs. 513 through 521)

2002Medical Device User Fee

and Modernization ActOffice of Combination

Products formed

1999ClinicalTrials.gov

founded1997

Food and Drug AdministrationModernization Act

2010ationrelated medical device legislation since 1976.PART VII Safety, StandardS, and Quality696

medical devices require CCC certification prior to SFDA registration.

ROLE OF STANDARDS IN MEDICAL DEVICE REGULATION

In almost all jurisdictions, standards are used for the detailed requirements used to regulate medical devices, and regulations are used to set the high-level principles. The exception is China, where the standards are written into the law and become part of the regulation.

predecessor of the present Department of Health and Human Services (DHHS). This study group, chaired by Dr. Theodore Cooper of the National Heart, Lung, and Blood Institute, estimated, as did other studies at the time, that over the previous decade more than 10,000 injuries and hundreds of deaths were linked to medical devices still on the market.4

Recommendations from this study group formed the basis of the Medical Device Amendments of 1976. The members of the group felt that performance standards would be more effective than a PMA in ensuring the safety and effectiveness of most new medical devices.

3supplemented the original Federal FD&C Act, which required a reasonable assurance of safety and effectiveness before a medical device can be marketed. Section 201(h) of the FD&C Act defined a medical device as:

An instrument, apparatus, implement, machine, contriv-ance, implant, in vitro reagent, or other similar or related article including any component, part or accessory which is (1) recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them, (2) intended for use in the diagnosis of disease or other con-ditions, or in the cure, mitigation, treatment, or preven-tion of disease, in man or other animals, or (3) intended to affect the structure of the body in man or other animals and which does not achieve any of its principal intended purposes through chemical action within or on the body of man or other animal and which is not dependent upon be-ing metabolized for the achievement of any of its principal intended purposes.

These amendments provided the FDA with the authority to regulate medical devices by establishing a three-tiered system of regulation. Manufacturers were required, at the very least, to register with the FDA any new low-risk device. High-risk devices, on the other hand, required PMA, and moderate-risk devices required PMN and FDA clearance prior to being marketed. In all cases, however, the FDA was required to conduct post-market surveillance of devices after introduction into clinical use, and manufacturers were required to report significant incidents to the FDA.

After the 1976 amendments, problems with an anes-thesia machine that led to the death of four patients exposed problems with the regulatory framework in place at that time. This led to congressional hearings and helped lead to the MDR regulations, issued shortly there-after, which required all manufacturers and distributors of medical devices to report deaths and serious injuries from medical devices to the FDA.5 During those hear-ings, the FDA agreed to work to minimize the dangerous use of medical devices, and real efforts for extending the FDAs Good Manufacturing Practices to cover the design of medical devices began.

A series of legislative changes have been made by Con-gress to the FD&C Act. They include: Safe Medical Devices Act (SMDA) of 1990 Medical Device Amendments of 1992 FDA Modernization Act (FDAMA) of 1997 Medical Device User Fee and Modernization Act

(MDUFMA) of 2002

Safe Medical Devices Act. The Safe Medical Devices Act (SMDA) was signed into law on November 28, 1990 (Public Law 101-629).6 Elements of the new law included user reporting of probable device-related issues, distrib-utor/manufacturer reporting of device incidents, changes to the 510(k) clearance and PMA processes, changes to the classification of devices, and changes to the FDAs internal performance standards process, recall authority, postmarket surveillance, and greater enforce-ment powers. One of the most important features of this law is that it imposed mandatory requirements on 4 StandardS and regulatory ConSiderationS 697

facilities that use medical devices. The user shared the onus, which previously only had fallen to the manufac-turer. Thus the FDA has gained some regulatory access and control in the local hospital. With this new law, the emphasis was supposed to have been moved from pre-market review to postmarket surveillance. Consistent with this change in philosophy, the processes by which devices are classified and approved were to have been relaxed. There is little evidence that this has happened. All institutionsfrom major medical centers to small, freestanding ambulatory surgical centersare now expected to report any information on the death or injury of a patient that may have been caused by a medi-cal device. Both the FDA and the manufacturer must be notified within a specified period of time and in a pre-scribed manner. In addition, institutions are required to produce biannual reports summarizing all individual reports filed over the past 180 days.

The SMDA made important changes in the law com-pared with the 1976 Medical Device Amendments, including certain changes in the requirements for all classes of medical devices. The Medical Device Amend-ments of 1992 were intended to clarify both the Medical Device Amendments of 1976 and the SMDA.

It is interesting to note that within the medical indus-try, medical devices are now subject to more stringent regulation than is the pharmaceutical industry. This is the case despite the fact that most of the recent congres-sional investigations and public scandals have been asso-ciated with pharmaceuticals.

MedWatch. The act causes the FDA to consolidate sev-eral adverse reaction reporting systems under the name MedWatch. The program is designed to provide a single portal for health professionals for the voluntary reporting of problems associated with medical devices. In this pro-gram, the FDA partners with a wide variety of organiza-tions, which are encouraged to play an active role in postmarketing surveillance.

Food and Drug Administration Modernization Act (FDAMA) of 1997. The FDAMA included provisions that require the FDA to accelerate review of devices. In response the FDA completed dozens of guidance docu-ments, most of which added requirements for manufac-turers. FDAMA included a mandate that the Center for Devices and Radiological Health (CDRH) create a stan-dards program, which has been very successful. FDAMA included provisions for regulation of advertising of unap-proved uses of drugs and devices as well as regulation of health claims for foods.

Medical Device User Fee and Modernization Act (MDUFMA) of 2002. The MDUFMA included provi-sions that permit the FDA to assess fees from sponsors of medical device applications for evaluation. In return the FDA agrees to improve performance to certain goals. MDUFMA included provisions for device establishment inspections by accredited third parties, and new require-ments emerged for reprocessed single-use devices. MDUFMA also included provisions that led to the for-mation of the Office of Combination Products within the

PART VII Safety, StandardS, and Quality698

Office of the Commissioner to oversee review of prod-ucts that fall into multiple jurisdictions within the FDA. An excellent review of the regulatory history of the FDA may be found in Section 2 of the recent Institute of Medi-cine (IOM) report.7 In late 2012, the MDUFMA was reauthorized for an additional 5 years. This reauthoriza-tion includes numerous incremental improvements to the device approval process.

Organization of the Food and Drug Administration

The FDA is an agency within the DHHS. It consists of the following centers and offices: Office of the Commissioner National Center for Toxicological Research Office of Operations Center for Veterinary Medicine Office of Medical Products and Tobacco Center for Devices and Radiological Health (CDRH) Center for Biologics Evaluation and Research

(CBER) Center for Drug Evaluation and Research (CDER) Center for Food Safety and Applied Nutrition Center for Tobacco Products Office of Regulatory Affairs

The parts of the FDA of most interest to anesthesiolo-gists include the CDRH (devices), CDER (drugs), and CBER (biologics/vaccines, gene therapies). The discus-sion will focus on the CDRH and its activities.

Center for Devices and Radiological Health. In 1982, the FDA established the CDRH, which was formed from elements of the old Bureau of Medical Devices and the Bureau of Radiological Health. The CDRH has evolved over the past 30 years and now has seven divisions, or offices, that report to the Directors Office: 1) Compli-ance, 2) Management Operations, 3) in Vitro Diagnostic Device Evaluation and Safety; 4) Surveillance and Bio-metrics, 5) Communication, Education, and Radiation Programs, 6) Science and Engineering Laboratories, and 7) Device Evaluation.

The Office of Device Evaluation (ODE) is responsible for the program areas through which medical devices are evaluated or cleared for clinical trials and marketing. These programs include PMA, product development protocol, humanitarian device exemption, investigational device exemption, and premarket notification programs. The ODE is presently divided into five scientific divisions: 1. Anesthesiology, General Hospital, Infection Con-

trol, and Dental Devices 2. Cardiovascular Devices 3. Reproductive, Gastro-Renal, and Urological Devices 4. Ophthalmic, Neurological, and ENT Devices 5. Surgical, Orthopedic, and Restorative Devices

Each division is further subdivided. The Anesthesiol-ogy, General Hospital, Infection Control, and Dental Devices division is divided into four branches, each with a separate branch chief.

Medical Devices Advisory Committee. The 1976 amendments also established the Medical Devices Advisory Committee, which currently consists of 18 medical device advisory panels that range from immunology to radiology for the purpose of advising the FDA on issues related to the safety and effectiveness of medical devices. These advisory panels include the Anesthesiology and Respiratory Ther-apy Devices Panel. Each panel has nine members in addi-tion to an FDA employee, who serves as the executive secretary. Seven of the panelists are voting members, and the consumer and industry representatives are nonvoting members. A panel can request consultants when necessary.

In 2010, the FDA changed the procedures of the med-ical device advisory panels. The panels are no longer being asked to vote on whether to recommend a medical devices approval or conditions of approval. Instead, they are being asked to vote on the devices safety and effec-tiveness and how the devices benefits compare with its risks. Typically, each of these attributes is voted sepa-rately with questions phrased along the lines of: 1. Do the data included in the product submission

provide substantial evidence of safety for the requested indication?

2. Do the data included in the product submission provide substantial evidence of effectiveness for the requested indication?

3. Do the available data indicate that the benefits out-weigh the risks of the device when used for the requested indication?

This change permits the panel members to focus on the scientific issues, which are more likely related to their expertise, instead of the regulatory issues with which they might not be familiar.

Classification of DevicesDifferent parts of the world use different classification approaches as illustrated in Table 34-2.

Europe

Europes classification system of medical devices is defined in EU directives on medical devices.8 These top-down classification rules are based on criteria such as the duration of contact with the patient (less than 60 minutes, not more than 30 days, and more than 30 days), the degree of invasiveness, and the part of the body affected by the use of the device.

United States

In the United States, the FDA was required to classify all medical devices into one of three categories per the 1976 amendments, based on the intended use of the device. Intended use refers to objective intent of the persons legally responsible for the labeling of a medical device. The FDA expects the intended use to address: The intended medical indication The intended patient population The intended part of the body or type of tissue

applied to or interacted with The intended user The conditions of use The operating principle

The class I to class III designations are used by the FDA to denote increasing scrutiny and controls. The classification of devices was originally determined by pan-els of experts, who advised the FDA following the adop-tion of the 1976 amendments. Of the initial 1750 generic types of devices classified, 40% were class I, 50% were class II, and 10% were class III. Device types were grouped into 16 medical specialties referred to as panels. The pan-els assigned each device type to one of the three regula-tory classes based on their assessment of the level of control necessary to assure the safety and effectiveness of the device. The classification is risk based, that is, the risk the device poses to the patient and/or the user is a major factor in the class to which it was assigned. Class I includes devices with the lowest risk, and class III includes those with the greatest risk. The class to which a device is assigned determines, among other things, the type of pre-marketing submission/application required for FDA clearance to market. If a device is classified as class I or II, and if it is not exempt, a 510(k) notification is required for marketing. All medical devices classified as exempt are not subject to premarket review, but the manufacturer is required to register the device with the FDA. For class III devices, a PMA is required unless the device is a pre-amendment device (on the market prior to the passage of the Medical Device Amendments in 1976, or substantially equivalent to such a device), in which case a 510(k) is

required. The FDA has nearly completed the task of either downgrading all preamendment class III devices into class II or calling for a PMA. Once this task has been completed, there will no longer be any class III preamend-ment devices on the market via the 510(k) process. In essence, the FDA classification system is bottom-up and based on the state of knowledge and medical devices in the late 1970s with some subsequent modification.

All classes of medical devices are subject to General Controls, which are the baseline requirements of the FD&C Act that apply to all medical devices, class I, II, and III.

Despite the congressional mandate to write perfor-mance standards for all class II medical devices, this task overwhelmed the CDRH, which had inadequate resources. In response the FDA gave tacit approval to existing national or international standards for this pur-pose. In doing so, the FDA was not relieved of the responsibility to formulate mandatory performance standards; however, they had indicated informally that their limited resources would not be used where volun-tary standards were in effect. The process by which the FDA was to develop a mandatory performance standard was quite complex and involved an FDA-appointed Standards Advisory Committee. To date, only the apnea monitor standard has been developed by this process.9 As such, voluntary standards were sought and have

tial equivalence (510[k]) or PMA

*Premarket (product control/tools for acknowledging product cleared for the market); placing on market (medical device/establishment control).

EC, European Commission; EEC, European Economic Community; PMA, premarket approval; PMDA, premarket drug approval.TABLE 34-2 Summary of Classification Systems anDevices in Selected Countries and Reg

Country Primary Agency Classification (

Canada Health Canada (www.hc-sc.gc.ca)

Food and DrugInvasive vs. noClasses I to IV

China State Food and Drug Administration (former.sfda.gov.cn). The General Administration of Quality Supervision, Inspection, and Quarantine is respon-sible for electrical safety

Regulations forMedical Devi

Class I: routine Class II: furthe Class III: strict Includes deviceused for life spose potentia

European Union

European Union (ec.europa.eu/)

Active ImplantaMedical DeviceIn Vitro DiagnoRisk-based clas

Japan Ministry of Health Labor and Welfare (MHLW) (www.mhlw.go.jp/english/)

PharmaceuticaClass I: generalClass II: certificClass II: approvClass III: approClass IV: appro

United States Food and Drug Adminis-tration (www.fda.gov)

Title 21 United Class I: general

Class II: performClass III34 StandardS and regulatory ConSiderationS 699

d Approval and Clearance Processes of Medical ions

Legal Basis/Classes)Premarket Placing on Market*

s Act (RSC, 1985, c. F-27)ninvasive vs. active devices

Establishment license

Device license the Supervision and Administration of ces (Decree 276 of State Council, 2000) administrationr controlcontrols implanted into the human body, those upport or sustenance, and those that l risk to the human body

Product registration certificate

Licensing of manufacturers and distributors

ble Medical Device Directive 90/383/EEC Directive 93/42/EECstic Medical Device Directive 98/79/ECsification

Compliance label (CE marking)

Responsible person registration

l Affairs Law

ationalvalval

PMDA NotificationThird-party certification

MHLW approval

States Code controls

ance standards/special controls

Establishment registration

Classification and finding of substan-

PART VII Safety, StandardS, and Quality700

become widely used, because they represent an excellent starting point. The use of externally developed voluntary consensus standards was helped by the Pentagon and its allies, who persuaded the Office of Management and Budget to issue Circular A-119 in 1982, urging federal participation in the development and use of voluntary consensus standards.10 Circular A-119 was revised and strengthened in 1993.

At present, it is noted that the CDRH believes that conformance with recognized consensus standards can support a reasonable assurance of safety and/or effective-ness for many applicable aspects of medical devices.11

The current list of recognized standards maintained on the FDAs Web site (www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm) and the standards program are managed by the CDRH Standards Manage-ment Staff (SMS). The SMS had been part of the Office of Science and Engineering Laboratories (OSEL) but was elevated to the Office of the Center Director in 2011. SMS is responsible for facilitating the recognition of national and international medical device consensus stan-dards within the CDRH and FDA. The CDRH standards program was created to address the Congressional man-date contained in the FDA Modernization Act (FDAMA) of 1997. SMS ensures appropriate medical device stan-dards are published in the Federal Register at least twice annually. Manufacturers are permitted to use recognized standards to simplify their premarket applications to the FDA. Although CDRH had been involved in the devel-opment of medical device standards for decades, FDAMA formalized the process.

Class I: General Controls. Class I medical devices were subject only to general controls to ensure safety and effectiveness. These controlling regulations 1) required that devices be registered; 2) prohibited adulteration or mislabeling of items; 3) provided for notification of risks, repair, replacement, or refund; 4) restricted the sale and distribution of certain devices; and 5) required GMPs as defined by the FDA.

Class II: Performance Standards and Special Con-trols. Medical devices in class II had to meet performance standards, because general controls were not considered sufficient to guarantee their safety and effectiveness. These devices had to fulfill all requirements of class I in addition to FDA performance standards.

Class III: Substantial Equivalence. A new class III medical device that was available commercially after the enactment date could attempt to claim substantial equivalence to an existing preamendment class III device and thus ride on the coattails of similar, older devices. This was provided for under section 510(k) of the FD&C Act. If a manufacturer chose the 510(k) route, the FDA needed PMN. Should the FDA have decided that substantial equivalence did not apply to the particular device, it had to be classified as a class III device. As such, it required PMA and review by the Anesthesiology and Respiratory Devices Review Panel before it could be marketed. The manufacturers only other option was to re-petition for reclassification of their device to class I or class II. The FDA generally ruled that a device was not substantially equivalent if 1) its intended use was different, 2) it raised new questions about safety or effectiveness, or 3) it did not perform as well as devices already on the market.

Classifying a Device in the United StatesTo find the classification of a device, the classification regulation for the device of interest needs to be found either using the FDAs on-line classification database (Web site) or using the device panel. Part 868, entitled Anesthesiology Devices, includes subparts for diagnostic, monitoring, therapeutic, and miscellaneous devices. Each classified device within each part has a seven-digit number associated with it, referring to the spe-cific code in Title 21 of the Federal Regulations, where it is defined. An anesthesia machine is listed under 21 CFR 868.5160 as a gas machine for anesthesia or analgesia and is defined as:

(a) Gas machine for anesthesia(1) Identification. A gas machine for anesthesia is a device used to administer to a patient, continuously or intermit-tently, a general inhalation anesthetic and to maintain a patients ventilation. The device may include a gas flowme-ter, vaporizer, ventilator, breathing circuit with bag, and emergency air supply.(2) Classification. Class II (performance standards).(b) Gas machine for analgesia(1) Identification. A gas machine for analgesia is a device used to administer to a patient an analgesic agent, such as a nitrous oxideoxygen mixture (maximum concentration of 70 percent nitrous oxide).(2) Classification. Class II (performance standards).

Premarket and Placing-on-Market ProcessesThe processes and tools used to evaluate a product before permitting its introduction to market vary con-siderably among countries (see Table 34-2). In the United States, the approval process (PMA) and mar-keting clearance (510[k]) of the FDA (see Table 34-1) are most often used to place products on the market in the United States. The EU requires compliance with its directives prior to applying CE-marking and the placement of a product in commerce. For medical devices, a manufacturer must demonstrate that the medical device meets the essential requirements of the Medical Device Directive8 by creating a technical file with the appropriate evidence and creating a Declara-tion of Conformity signed by a representative of the company prior to introduction. For manufacturers outside the EU, this material must be accessible to a designated Authorized Representative within the EU. The CE-marking approach is intended to ensure free movement of goods and services within the European common market.

Canada requires obtaining a license with the process similar to that of the 510(k) in the United States, from a paperwork perspective. In Asia a wide variety of listings,

3registrations, and approvals for medical devices exist that range from a simple addition of the medical device to a list to very involved approval processes that require in-country clinical evaluations.

Pending Regulatory Changes in the United StatesWhat is happening in the United States with respect to changes in to the 510(k) and other processes? Following a 1-year internal assessment in August 2010, CDRHs 510(k) Working Group published a preliminary report12 consisting of more than 60 recommendations grouped under six findings aimed at improving the Centers effectiveness in implementing its various missions. The preliminary report focused on three major areas: the need for 1) a rational, well-defined, and consistently interpreted review standard; 2) well-informed decision making; and 3) continuous quality assurance. The report found: 1. There is insufficient clarity with respect to the defi-

nition of substantial equivalence. 2. CDRHs current practice allows for the use of some

types of predicates that may not be appropriate. 3. The de novo pathway is important and has not been

optimally used across the Center. 4. It is challenging for reviewers to obtain the infor-

mation they need to make well-supported clearance decisions.

5. The CDRHs knowledge management infrastruc-ture is limited.

6. Variations in the expertise, experience, and training of reviewers and managers, including third-party reviewers, may contribute to inconsistency or uncertainty in 510(k) decision making.

The report committed the FDA to create a large num-ber of new or revised guidance documents aimed at improving the 510(k) program.

The FDA also commissioned the IOM to evaluate the current 510(k) process to see whether it protects patients and promotes innovation, and if not, to evaluate what legislative, regulatory, or administrative changes are rec-ommended to best achieve the goals of the 510(k) pro-cess. The IOM report includes an excellent summary of the history of the reform of the 510(k) process. It was issued in July of 2011 and found that the current 510(k) process: Does not determine safety or efficacy of a medical

device Lacks the legal basis to screen a medical device for

safety and efficacy Was never intended to do either of the above

The IOM report indicated that rather than continu-ing to modify the 35-year-old 510(k) process, the IOM concludes that the FDAs finite resources would be better invested in developing an integrated premarket and post-market regulatory framework.7 The day the IOM report was published, the FDA immediately rejected its conclu-sion and announced the 510(k) process should not be eliminated, but the FDA is open to additional proposals and approaches for continued improvement of our device review program.134 StandardS and regulatory ConSiderationS 701

The FDA has continued to follow through on its commitments from the 510(k) preliminary report with the following objectives: Create new or update existing guidances for clarity Integrate systems and databases to make informa-

tion more accessible Issue regulations to cover previously neglected

items and transfer of ownership of a 510(k).13

MEDICAL DEVICE VOLUNTARY STANDARDS

OverviewWork on standardizing medical equipment began because of incompatibilities that became obvious during World War II.10 Voluntary consensus standards for medical devices have been in use for the past few decades, and commercial standards have existed for well over 100 years. These standards often codify commonly used and long-standing practices. Commercial standards may be developed solely within a company, by a trade group, or by a technical society. Generally, in the United States the writing of standards is essentially a bottom-up process that formalizes existing and accepted commercial or industrial processes and experience.

On the international level, standards are dichotomized much as they are nationally. Older multinational stan-dards organizations, such as the International Organiza-tion for Standardization (ISO) and the International Electrotechnical Commission (IEC), work on the basis of voluntary consensus. ISO members are the National Standardization Institutes of 163 countries and its staff at the Central Secretariat in Geneva, Switzerland, coordi-nating and supporting the creation and marketing of ISO standards. ISO member bodies (www.iso.org/iso/about/iso_members.htm) may directly develop standards (e.g., Germanys DIN and the United Kingdoms BSI) or may delegate another body to do so (e.g., ANSI in the United States; Table 34-3). Other newer, multinational organi-zations with official regulatory authority are now emerging.

The arena of voluntary consensus standards for medi-cal equipment may not appear as orderly and regimented as that of government regulation. In fact, it can be a source of considerable confusion to the practicing anes-thesiologist. This is especially true when an anesthesiolo-gist wants to determine the current voluntary consensus standard for a particular piece of equipment. Several dif-ferent sets of voluntary standards from a number of dif-ferent organizations often apply to a single medical device (Table 34-4). Even the alphabet soup used to describe the different organizationsAAMI, ANSI, NFPA, IEEE, IEC, ISO, and ASTMcan be confusing.

Development of standards by the voluntary consensus method is faster and more responsive to the marketplace than methods used by either state or federal agencies. Organizations that propose voluntary standards are not subject to the cumbersome bureaucratic and legal intrica-cies that govern both federal and state governments. This is not to say, however, that voluntary consensus organizations

can be cavalier or ignorant with regard to legal require-ments. In the interest of fairness and to prevent legal rami-fications, all interested parties are allowed to participate in the process of creating standards in accordance with the individual organizations bylaws.

Compliance with voluntary standards is not manda-tory, because the parent organization has no legal juris-diction. Voluntary consensus standards, however, often have an influence even before they are finalized. Respon-sible manufacturers find both legal protection and sales

AAMI U.S. TAG for IEC/SC 62D SafetyANSIIEEE EMB/11073 CommunicationsNEMA MITANCCLS Radiology, in vitro diagnosticsCGA

United States (foreign) BSI, DIN, JISC, SAC, ABNT TC 121 AnesthesiaRegional CEN (EU) TC 215 ISO TC 121 mirror

CENELEC (EU) TC 62 IEC TC 62 mirrorInternational ISO TC 121; TC 210 Anesthesia; quality systems

and risk managementIEC SC 62A, 62D Electrical aspects

AAMI, Association for the Advancement of Medical Instrumentation; ABNT, Associao Brasileira de Normas Tcnicas (Brazilian Association of Technical Standards); ANSI, American National Standards Institute; ASTM, American Society for Testing and Materials; BSI, British Standards Institute; CEN, Comit Europen de Normalisation (European Committee for Standardization); CENELEC, Comit Europen de Normalisation lectrotechnique (European Committee for Electrotechnical Standardization); CGA, Compressed Gas Association; DIN, Deutsches Institut fr Normung (German Standards Institute); IEC, International Electrotechnical Commission; IEEE; Institute of Electrical and Electronic Engineers; ISO, International Organization for Standardization; JISC, Japanese Industrial Standards Committee; MITA, Medical Imaging and Technology Alliance; NCCLS, National Clinical and Laboratory Standards Institute; NEMA, National Electrical Manufacturers Association; SAC, Standard-ization Administration of China; SC, Scientific Committee; TAG, Technical Advisory Group; TC, Technical Committee.

TABLE 34-4 Selected Recognized, Harmonized, and Particular Standards in Relation to Technology

FDA MDD

Equipment

Latest International Particular Standard (ISO, IEC, ASTM)

Product Code(s)*

Recognized Con-sensus Standard

Harmonized Standard

Related Clinical Guidelines

Anesthesia workstation

IEC 60601-2-13: 2011 BSZ IEC 60601-2-13 Ed 3.1: 2009

EN 60601-2-13: 2006 Machine checklist, obsolescence, gas disposal (ASA, FDA, institutional, government)

Anesthetic agents monitor

IEC 80601-2-55: 2011 CBQ, CBS, CBR ISO 21647: 2004 EN ISO 21647: 2009 Regulatory bodies with respect to gases

Carbon dioxide monitor

IEC 80601-2-55: 2011 CCK ISO 21647: 2004 EN ISO 21647: 2009 AARC (CPG, 2011) Numerous anesthesia guidelines for different settings (e.g., ASA)

Pulse oximetry IEC 80601-2-61: 2011 DQA ISO 9919: 2005 EN ISO 9919: 2009 CLSI (POCT11-A2)IEC 80601-2-61 AARC (CPG-1992)Ed 1.0: 2011 ASA

Oxygen monitor

IEC 80601-2-55: 2011 CCL ISO 21647: 2004 EN ISO 21647: 2009 AARC (various CPGs)

*Per http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm.As of March 1, 2012, per http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm.As of March 1, 2012, per http://ec.europa.eu/enterprise/policies/european-standards/harmonised-standards/medical-devices.AARC, American Association for Respiratory Care; ASA, American Society of Anesthesiologists; CLSI, Clinical Laboratory and Standards Institute; CPG, clinical practice guideline; EN, European Committee standard designator; FDA, Food and Drug Administration; IEC, International Electro-technical Commission; ISO, International Organization for Standardization; MDD, Medical Device Directive; POCT, point-of-care testing.PART VII Safety, StandardS, and Quality702

TABLE 34-3 Selected Standard Development Organ

Scope Organizations

United States (domestic) ASTMizations of Interest to Anesthesia

Committee of Interest Committee Focus/Comment

F29 Anesthesia

among the member bodies of an organization. It may be used as such, or it may be implemented through incorpo-ration in national standards of different countries. Inter-national standards are developed by technical committees and subcommittees. Many such committees follow a six-step process. The six-step process followed by ISO affili-ated committees is shown in Figure 34-2 with the activity, documents, and elapsed time for each stage noted.14 ISO standards are reviewed at the least 3 years after publica-tion and every 5 years thereafter by all the ISO member bodies. A majority of the participating members of the technical committee (TC) or scientific committee (SC) decides whether an international standard should be con-firmed, revised, or withdrawn.

Within organizations such as ISO, standardization is an open, voluntary process built around consensus, and it is stakeholder driven. Within the ISO, the committee of rele-vance to anesthesia is TC 121, Anaesthetic and Respiratory

Proposal stage

Activity in stage

Elapsed time(months) (default)

Preparatory stage Committ

Formal voting by ISOmember bodies

whether to work ondocument

ISO Technical Committee time -Document being developed inrelevant committee.

ISO CentraDocument evaluation,

Building expertconsensus

Consensuwithin C

114131210 1198765431

WD CDStageMonth 2

1 - New work ItemProposal (NWIP)

2 - Working Draft(s)(WD)

3 - Committe(CD

FIGURE 34-2 nThe consensus-building stages of standards. Note: Cnational Standard documents are approved only if a two-thirds mscientific committees are in favor, and not more than one quarter which for ISO is a member body and for IEC is a national committee, accepts responsibility for administering the JWG, and that organization holds the secretariat and appoints one or two individuals to handle the technical and administrative work. A convenor (chairman) runs the meetings and works to reach consensus. Frequently a JWG has a secretary who manages the documents and works closely with the convenor.

Within each committee, and as part of the standards development processes, are important roles to play, both nationally and internationally. Clinician involve-ment is crucial to the development and revision of med-ical device standards. Participation can be as an expert in a working group, a member of a national delegation, and even as a head of a national delegation. Experts attend meetings in their own capacity as experts, but they must be aware of the position of the national body of the country they represent. Influence may be wielded

ee stage Enquiry stage Approval stage Publication stage

l Secretariet time-being processed (e.g.,editing, and proofreading).

ISO Member body time-Document circulated to ISOmember bodies for DIS/FDIS vote.

s buildingommittee

Commenting andformal voting on

document within ISOFormal vote by ISO

member bodies

3634 353332313029282726252423222120191817165

DIS FDISCommentsresolution

e Draft(s))

4 - Draft InternationalStandard (DIS)

5 - Final DraftInternational Standard

(FDIS)6

International Standard

ommittee draft, draft International Standard, and final draft Inter-ajority of the participating member bodies of the technical and

of the total number of votes cast are negative.34 StandardS and regulatory ConSiderationS 703

advantages in claiming that their equipment meets vari-ous voluntary standards, such as those of AAMI, ANSI, IEC, ISO or ASTM. New voluntary standards cannot require that a manufacturer remove from the marketplace earlier equipment that does not conform to the new stan-dard. Only a municipal, state, or federal authority having jurisdiction can demand compliance or remove an item from the market. Often, voluntary consensus standards, such as those of the National Fire Protection Association (NFPA), are adopted by local agencies that have the authority to turn the standards into law. Voluntary equip-ment standards can also be adopted by a government agency as part of their procurement or purchasing poli-cies. On occasion, however, a governmental regulation may be adopted before the voluntary standard has been finalized.

Stages in the Development of International StandardsAn international standard is the result of an agreement

Equipment. The stakeholders in TC 121 include equip-ment manufacturers, clinicians, regulatory agencies, test houses, and others. Created in 1966, TC 121 has a scope defined as standardization of anaesthetic and respiratory equipment and supplies, related devices, and supply sys-tems. It is responsible for 85 standards among its subcom-mittees (see Table 34-3) and includes 25 participating and 24 observing countries. Also of importance is the IEC, which has a committee responsible for developing interna-tional standards for electrical equipment used in medical practice (IEC TC 62), whose subcommittee D is responsi-ble for electromedical equipment (e.g., the nonradiology particular medical electrical device standards of the 60601-2 series).

Given the wide variety of equipment on the market, it is often not clear which organization should be responsi-ble. So that the expertise of both organizations may be made available in the development of standards, joint working groups (JWGs) between ISO and IEC are often formed. In these cases, either ISO or IEC may take the lead. For each JWG, one of national standards bodies,

PART VII Safety, StandardS, and Quality704

through formal approacheswritten comments, discus-sions, drafting of resolutions, and votingand by infor-mal means, such as lobbying members of other delegations and through personal relationships.

Organization of Standards Development OrganizationsThe scope of standards that the standards development organization (SDO) develops varies considerably. It may represent a technical area (e.g., electrical, pneumatic), or it may be application oriented (e.g., clinical). Sometimes the scope may not be clear. In the case of ISO and IEC, the technical divisions are often not clear, and JWGs exist to allow members of both bodies to participate. Agree-ments have been signed between different regional and international SDOs to help clarify the roles and responsi-bilities to reduce duplicative activities and promote coop-eration. The Committee for European Standardization (CEN) and Committee for European Electrotechnical Standardization (CENELEC) have agreements with their international counterparts, ISO and IEC, defining the rules governing cooperation. The Vienna (1991) and Dresden (1996) Agreements signed between CEN and ISO and CENELEC and IEC, respectively, helped to create the framework for cooperation between European and international standards activity with the explicit rec-ognition of the primacy of international standards and goal of simultaneous recognition at the international and European level.

For in vitro diagnostics, the Clinical and Laboratory Standards Institute (CLSI), formerly the National Com-mittee for Clinical Laboratory Standards (NCCLS), develops the preponderance of relevant standards. The CLSI also is the international secretariat of ISO TC 212, Clinical Laboratory Testing and In Vitro Diagnostic Test Systems, which gives CLSI a pathway to have its standards become European standards via the Vienna Agreement with CEN.

Other standards or guidelines may be developed pri-marily by medical societies, which include societies such as the American Thoracic Society, American Society of Anesthesiologists (ASA), and American Association for Respiratory Care.

Standards come into existence in three ways: 1) by national or international recognition (ISO, IEC, ASTM, etc.); 2) by common use (de facto standards, such as MS Windows), and 3) by industry consortia.

SDOs have certain defining characteristics. First, they follow a very formal standards development process. Sec-ond, they have broadly inclusive participation structures composed of representatives from all members of a given class, because an international SDO must include a repre-sentative from each nation. Third, open discussion and debate occurs on all issues, and due process gives mem-bers the opportunity to lodge formal complaints and appeals to the establishment of given standards. Finally, democratic voting procedures are available that empha-size consensus as opposed to majority or plurality rule. Because of these characteristics, standards issued by SDOs have a high degree of legitimacy, derived from the process that created them.SDO standards do offer stability and support. On the other hand, these same characteristics generate criticism of SDOs, which are often too slow with respect to market time frames. Redundant and parallel structures exist, especially within the country representatives to interna-tional SDOs. Therefore SDOs are inefficient; they are too focused on consensus and hence are often reduced to choosing the least common denominator, which often is not an ideal solution to many users. Voting structures are out of sync with the economic investment of participating members, and participation of nonstakeholder members drags out the process. SDOs cost too much (e.g., AAMI), and their processes are out of date. While technically apt, committee members lack experience and writing skills to produce draft standards quickly, and SDOs do not effec-tively prioritize drafts that need to be considered first. Unlike European and Pacific Rim countries, the United States is not represented at international standards orga-nizations by any official governmental representative, and the United States does not have a single body that speaks for all standards activities within the country.

At present ANSI serves as the coordinator and formal representative for the United States before the ISO and the IEC. However, ANSI delegates the responsibility for actually doing the work to other SDOs within the United States (e.g., AAMI, ASTM, CLSI). The General Agree-ment on Tariffs and Trade (GATT), to which the United States has been a signatory since the late 1940s, was replaced by the World Trade Organization (WTO) in 1994. Under these international trade agreements, there exists a Standards Code that provides ground rules for preparing, ratifying, and implementing international technical standards to be used to prevent technical barri-ers to trade. ANSI has assumed the role of representative for the United States, but in contrast to many of its coun-terparts in Europe, it has no official governmental sanction.

Several non-U.S. SDOs of interest include both regional (e.g., CEN and CENELEC) and national SDOs (e.g., DIN, BSI), which also may serve as the ISO or IEC member body.

U.S. Standards Development Organizations of InterestAmerican National Standards Institute (ANSI)

The anesthesia community has a long history of involve-ment with ANSI, a private, nonprofit organization founded more than 70 years ago to coordinate and facili-tate the development of standards. In 1956 the ASA assumed the secretariat of ANSI Committee Z-79 for Anesthesia and Respiratory Therapy Equipment, and they maintained this position until 1983. During this time, many standards were produced by the Z-79 Com-mittee, including those for humidifiers, reservoir bags, ventilators, tracheal tubes, and anesthesia machines. Prob-ably the most important and best-known standard created by the Z-79 Committee was the Z-79.9 1979 standard for anesthesia machines.15 This was the first attempt by the manufacturers and users of anesthesia equipment to ensure compatibility and performance among the various

34 StandardS and regulatory ConSiderationS 705types of anesthesia machines. Although this standard con-tained flaws, it was the best standard that could be devel-oped at the time through voluntary consensus efforts. However, the standard was deficient in some major areas. For example, it permitted the use of in-circuit vaporizers and required neither oxygen analyzers nor a method to prevent the administration of a hypoxic mixture. It did, however, serve the anesthesia community well, both man-ufacturer and user, during the 10 years it functioned as the ruling anesthesia machine standard. National standards activity in this area was transferred by committee vote in 1983 from ANSI to ASTM.

ASTM International

Formerly the American Society for Testing and Materi-als, ASTM International currently handles most of the activities concerning voluntary standards that affect anes-thesia durable equipment. Committee F-29 on Anes-thetic and Respiratory Therapy Equipment has 10 subcommittees that focus on safety and performance standards rather than on design or specific engineering standards. Design and engineering decisions are best left to the individual manufacturer. ASTM views standards-writing activities as a method to achieve an orderly approach to a specific activity or problem. All committee members are volunteers; the formal ASTM staff provides only administrative support. ASTM does not fund any participants, nor does it have its own laboratory facilities; individual members must have their own funding. At present, the ASA funds the travel of its liaison to Com-mittee F-29.

Under ASTM bylaws, the members of any committee should reflect a balance of users, producers, ultimate con-sumers, technical representatives, insurers, educators, and those with an interest in the area. The last category can include members of the FDA or of nonprofit health care organizations that deal with medical devices directly or indirectly.

Almost anyone can initiate the creation of a standard within ASTM. The proponent must first submit a written request detailing the various companies, individuals, and organizations participating. The executive staff of ASTM then decides whether the proposal has merit. If accepted, the proposal is then referred to a particular committee.

Association for the Advancement of Medical Instrumentation (AAMI)

AAMI is a nonprofit organization founded in 1967. It is a unique alliance of more than 6000 members from around the world united by one mission: to provide global multi-disciplinary leadership and programs that enhance the goals and capabilities of the professions, health care insti-tutions, government, industry, and other organizations that relate to the delivery, development, management, use, and other aspects of safe and effective medical instru-mentation and related technologies. The AAMI standards program consists of over 100 technical committees and working groups that produce Standards, Recommended Practices, and Technical Information Reports for medical devices. Standards and Recommended Practices represent a national consensus, and many have been approved by ANSI as American national standards. AAMI also admin-isters a number of international health care technical committees of ISO and IEC in addition to U.S. Technical Advisory Groups (TAGs).

National Fire Protection Association (NFPA)

The anesthesia community has been involved with volun-tary standards for almost 40 years. Initially, the ASA par-ticipated in the development of standards by the NFPA, which writes standards for many aspects of fire preven-tion, detection, and suppression. The NFPA also addresses standards for different types of facilities, such as multiple dwellings, factories, and hospitals. Initially, when cyclopropane and ether were used in operating rooms (ORs), the input of anesthesiologists was impor-tant in developing standards for anesthetizing locations. Their input was again needed with the advent of central-ized medical-gas distribution systems, such as for oxygen and nitrous oxide. What initially developed as fire safety regulations for all occupants of a facility eventually evolved into patient safety standards. An example of this is the present NFPA standard for nonflammable medical-gas piping systems.

Anesthesiology input has remained vital to the NFPA throughout the years, both to provide user input and to ensure that proposals by fire professionals for changes or modifications do not adversely affect the hospitals clini-cal practice. For instance, a firefighter cannot elect to turn off the hospitals entire oxygen supply because of a fire in one wing of the facility. Obviously, the drafting of such a standard requires compromise on the part of both clinicians and fire professionals.

All standards published by the NFPA that affect hospi-tals are now published in one document: the NFPA 99 Health Care Facilities Code.16 This document is gener-ally updated every 3 years and was most recently updated in 2012. It contains standards governing anesthetizing locations, emergency power supplies, high-frequency electricity, medical-gas pipeline systems, and hyperbaric oxygen facilities.

In the newest edition, NFPA-99 has changed from a standard to a code. It has been rewritten to be a risk-based, rather than an occupancy-based, document. That means the requirements are based on whether a system failure would cause a high, moderate, or low risk to a patient. Therefore wherever general anesthesia is being administered to patients, appropriate back-up systems must be in place for things such as oxygen and electrical power: it no longer matters if the facility is a 50 OR medi-cal center or a two-room freestanding outpatient facility.

Other changes to NFPA-99 include a provision that all new or remodeled ORs will default to being a wet location. That means that special electrical protection in the form of isolated power or ground fault circuit inter-rupters (GFCIs) will have to be installed, unless the facil-ity does a risk assessment to prove that certain ORs are not wet locations. Other relevant changes include a requirement for all electrical/gas booms to be inspected on a regular basis and for a minimum of 18 electrical out-lets to be installed in a critical care area and 36 in an OR.

PART VII Safety, StandardS, and Quality706

Although ether and cyclopropane are no longer used in modern ORs, the threat of fire has in no way been eliminated. Each year the amount of electrical equipment in the OR increases. Many of these devices, such as elec-trosurgical units (ESUs) and lasers, can ignite drapes, sponges, and other disposable items in an OR. In the presence of oxygen or nitrous oxide, a spark can become a conflagration (see also Chapter 31). A number of orga-nizations have become interested in the prevention of OR fires. In 2008 the ASA issued a Practice Advisory on OR fire prevention.17 Also, in 2010 the Anesthesia Patient Safety Foundation (APSF; www.apsf.org) produced a video with new recommendations on the prevention of OR fires, Prevention and Management of Operating Room Fires. Other organizations that have made efforts to pre-vent OR fires include the ECRI Institute18 and the Asso-ciation of Operating Room Nurses (AORN).

Institute of Electrical and Electronics Engineers (IEEE)

The IEEE has traditionally written standards that directly concern only engineers. One project within IEEE of particular interest to the anesthesia commu-nity concerns the work of IEEE Committee P-1073, which has been developing medical communications standards since 1987; the idea originated during the early 1980s, after the AAMI sponsored a roundtable discussion in 1982 on developing standards for data management in monitoring. Many of those attending the session thought that a standardized method for data communication among monitoring equipment was needed in the OR. A proposal was subsequently made by the AAMI Standards Board that a technical commit-tee be formed to develop standards for monitoring sys-tem data management. However, no further action was taken by AAMI.

In 1987, this subject was taken up by Committee P-1073 of the IEEE Engineering in Medicine and Biol-ogy Society (EMBS), which consisted of device manufac-turers, computer experts, clinicians, and biomedical engineers. The Committee undertook to produce stan-dards for local area networks (LANs) to enable communi-cation among freestanding monitors, infusion and life-support devices, and a host computer system. This was not to serve laboratory or pharmacy functions but rather was intended solely to support the clinician in an acute patient-care setting, such as the intensive care unit (ICU) or OR.

These standards specifically make provisions for anes-thesia machines and ventilators with the purpose of developing an automated anesthesia record using local intelligence, which can be uploaded to a large host com-puter system. The goal is to eliminate the need for indi-vidual institutions to write software or design connectors for devices. The standards therefore are vendor independent.

It has taken more than two decades, but Committee P-1073 has written a series of standards for point-of-care medical device communication, the IEEE 11073 series, many of which have also been adopted by ISO TC 215, Health Informatics.Medical Device StandardsISO and IEC standards follow the same basic structure: Scope defines without ambiguity the subject of the

standard and the aspects covered, thereby indicat-ing the limits of applicability of the standard.

Normative references give a list of the referenced documents cited in the standard in such a way as to make them indispensable for the application of the standard.

Terms and definitions give the definitions necessary for the understanding of certain terms used in the standard.

Requirements contain clauses that have all of the dic-tates, statements, and recommendations or refer-ences to them necessary to claim compliance to the standard.

Annexes, both normative and informative, give pro-visions additional to those in the body of the docu-ment. Annex AA, which is found in many ISO and IEC health care standards, contains particular guid-ance and rationale that includes useful explanations to the reader and user of the standard. This allows an interpretation more aligned to what was intended by the developer of the standard. Another annex commonly found is an Annex reference to the essential principles (of ISO 16142).

The General Standard (60601-1)

The IEC 60601-1, developed by IEC TC 62, is a family of technical standards for the basic safety and essential per-formance of medical electrical equipment, comprising the general standard, a series of 11 collateral standards, and over 70 particular standards. At present, three editions have been published: the first in 1977, the second in 1988, and the third in 2005. The general standard is formally known as IEC 60601-1, Medical Electrical Equipment, Part 1: General requirements for basic safety and essential performance.19 IEC 60601-1 contains the general require-ments for medical electrical equipment. Compliance with IEC 60601-1 has become a de facto requirement for the commercialization of electrical medical equipment in many countries. It is harmonized with the MDD, needed for CE-marking, and is recognized by the FDA.

Although this is an international standard, each coun-try does have the right to recognize the standard in whole or with deviations, changes to specific clauses, for country- specific requirements. The deviations may be minor or significant. The U.S. deviations are published as a cover to the international standard and are known as AAMI ES 60601-1.

The latest edition of this standard, the third edition, was published in 2005. It resulted from an understanding of the recognized deficiencies of the second edition and in particular the need to address the safety performance of medical electrical equipment. It is the work of 11 working groups involving over 200 people over a period of 10 years.

Key changes in the third edition include the overall structure and the numbering scheme of the clauses. The application and visibility of risk management was increased by adding requirements for the establishment

Collateral standards (Table 34-5) have been created over the years to add requirements for a subgroup of equipment, such as for certain safety and performance aspects specific to environments of use (e.g., home care), or related to a

60601-11Closed loopphysiologiccontrollers

60601-8Alarm systems

60601-2EMC

60601-1General

requirements

General standard and itscollaterals (part 1) Paa time), and hypoxia prevention systems. Additionally, many aspects of the anesthesia machine that have been made standard often directly relate to solving known problems or helping to reduce use errors. Over time

FIGURE 34-3 nOrganization of Inter-national Electrotechnical Com-mission 60601, its collaterals, and particular standards. Note that the particular standard is dominant and amends the general standard and its collaterals.

80601-2-13Anesthetic

workstations

80601-2-55Respiratory gas

monitors

rticular standards (part 2)34 StandardS and regulatory ConSiderationS 707

of a risk management process per ISO 14971, the estab-lishment of acceptable levels of risk, and demonstration that the residual risks are acceptable (according to the manufacturers policy for determining acceptable risk).20 The concept of essential performance (EP) or safety-related performance was introduced and defined as the performance of a clinical function, other than that related to basic safety, where loss or degradation beyond the limits specified by the manufacturer results in an unacceptable risk.19 EP is most easily understood by considering whether its absence or degradation would result in an unacceptable risk. The process of creating third editioncompliant versions of all of the related pub-lished standards is ongoing, and manufacturers and users of the standards will have to deal with both the second and third edition versions of the particular standards until the transition periods in all countries are completed.

For many specific product types, a standard has been developed using the general standard as a template with additions, deletions, and changes made to specific clauses, thereby creating what is known as a particular standard, numbered as IEC 60601-2-xx, where xx references the particular device. Where the particular standard is the product of an ISO/IEC joint working group, the standard can be numbered 80601-2-xx, with either an ISO or IEC prefix, determined by which organization had the lead for the work. This is shown graphically for a couple of devices in Figure 34-3.

specific characteristic of all equipment not fully addressed in IEC 60601-1 (e.g., alarm systems or electromagnetic capability [EMC]). For an FDA perspective on the role of standards in medical devices EMC, see Silberberg.21

Standards of Particular Interest

Particular standards take precedence over the general standard and collateral standards. Standards of particular relevance to anesthesia are numerous. A number of these standards that are the domain of TC 121 (Table 34-6) are shown in Table 34-7. In addition, the breadth of coverage of these standards is shown graphically in Figure 34-4. This section highlights the key aspects and history of three standards of particular interest to anesthesiologists: 1) anesthetic workstations, 2) respiratory gas monitors, and 3) pulse oximeters. These medical device standards and other standards can be given much of the credit for the reduction in mortality and morbidity from anesthesia over the past 30 years. These standards have included important safety innovations, such as the introduction of the diameter index safety system for connections for medical-gas hoses; the pin index safety system for medical-gas cylin-ders with post-type valves and cylinder mounting yokes; color coding of gas cylinders and equipment; and the incorporation of various fail-safes and protective features, such as the keyed filling system for vaporizers, vaporizer interlocks (which permit the use of only one vaporizer at

PART VII Safety, StandardS, and Quality708the addition of monitors, anesthesia machine checkout procedures, and the use of anesthesia simulators for teaching have helped increase patient safety. These mon-itors include airway pressure monitors, tidal volume monitors, oxygen analyzers positioned to sample inspira-tory gases, carbon dioxide analyzers placed to monitor exhaled gases from the patient, and pulse oximeters.

Anesthetic Workstations. Table 34-8 highlights the changes in anesthesia machine/workstation standards, both U.S. and international, and their sequence since the advent of ANSI Z-79.8, the first anesthesia machine stan-dard.15 Activity on the Z-79.8 standard began in about 1970, as members on the Z-79 Subcommittee on Perfor-mance of Anesthesia Gas Machines sought and collated the problems which are being experienced with appara-tus throughout the country, as a first step in the evolution of pertinent performance specifications22 and concluded with the publication of Z-79.8 in 1979, because the time (was) long overdue for action on gas machine perfor-mance and safety standards.23 The committee work on Z-79 for the anesthesia machine gave rise to a number of standards,24 including those for humidifiers25 and 15- and 22-mm connectors. When the F1161-88 standard26 was published about a decade later and followed by F1850-0027 in 2000, many in the anesthesia and regulatory com-munity hoped that all gas machines predating the Z-79 standard would be retired. Recent studies have shown this not to be the case. It is unfortunate that many anes-thesia machines more than 30 years old are still being used in obstetrical units, radiology suites, and emergency rooms, even though they do not reflect the current state

Controllers used to control the parameters they are measuring. Such systems have to be stable, reliable, and fault tolerant. Software must be designed methodically and validated comprehensively.

60601-1-11: 2010 Home Health Care Equipment

Puts considerable emphasis on the use of home health care equipment by non-specialist users. Electrical safety is also a factor here and the equipment must be tolerant of poor wiring in the building and wide environmental limits.

60601-1-12 Ed 1 (under development)

Equipment for Use in Emergency Medical Services Environment

Puts considerable emphasis on the use of emergency medical equipment by users in crisis situations. Electrical safety is also a factor, and the equipment must be tolerant of the extremely wide environmental limits that can be found at the scene of an emergency.

*Modified from http://www.mddionline.com/article/collateral-standards-iec-60601-1.

TABLE 34-6 Subcommittees of TC 121

Subcommittee/Working Group Title

CAG Chairman Advisory GroupSC 1 Breathing Attachments and

Anaesthetic MachinesSC 2 Airways and Related EquipmentSC 3 Lung Ventilators and Related

EquipmentSC 4 Terminology and SemanticsSC 6 Medical Gas SystemsSC 8 Suction Devices for Hospital and

Emergency Care UseTABLE 34-5 Collateral Standards

Collateral Standard: Year of Latest Edition Title Comment

60601-1-1 Medical Electrical Systems Discontinedition.

60601-1-2: 2007 Electromagnetic Compat-ibility (EMC)

Complianunwant

60601-1-3: 2008 Radiation Protection for Diagnostic X-ray Systems

Ensures tsafety o

60601-1-4 Programmable Electrical Medical Systems (PEMS)

This is a cstand-aedition.

60601-1-6: 2007 Usability Increasesrequireincidencontrol

60601-1-8:2007+A1: 2012 Medical Alarm Systems Gives guiof alarmchaoticalarm c

60601-1-9: 2008 Environmentally Conscious Design

Design prof the atranspo

60601-1-10: 2008 Physiologic Closed Loop Design prs*

ued as a stand-alone document; incorporated into the third

ce means that the equipment will neither generate excessive ed electromagnetic radiation nor be unduly affected by it.hat radiation is kept as low as reasonably achievable for the f patient and operator.

ollateral standard for software. It has been discontinued as a lone document and is now incorporated into the third

emphasis on ergonomics; manufacturers must take the ments into account during the design phase. Many adverse ts in the past have been traced to use error; intended to risks caused by usability problems.dance and requirements in the prioritizing and management functions in medical equipment. Alarm systems can be if the user does not know what is going off and whether the ondition is trivial or serious.ocess requiring the manufacturer to consider contamination ir, water, and biosphere; the use of raw materials; and rt and packaging in the design of new products.ocess to be considered when designing medical devices

of technology. Although obsolescence is difficult to define, a gas machine that has been in operation for more than two decades should be retired, because it will be missing many important safeguards. Failure to retire an outdated machine can significantly jeopardize the safety of the patient, and it can create liability issues for the anesthesia provider and the institution. Unfortunately, no legal mechanism exists to ensure that such equipment is not used.

In 1990 CEN began working on a standards project entitled Anesthetic Workstations and Their Modules: Essential Requirements. The Anesthetic and Respira-tory Devices Committee of ISO was actively involved in the development of this European standard, which estab-lished the important safety and performance require-ments for anesthetic workstations, or anesthetizing locations, as they are known in the United States. The standard, EN 740:1999, outlined the complete require-ments for individual modules that together constitute a complete anesthetic workstation (i.e., anesthesia ventila-tor, breathing system, scavenging system, vaporizers,

monitors, and alarm systems). Here, the goal was not to specify a universal world anesthesia machine but rather to ensure that each component used clinically meets mini-mum, specific, identifiable requirements. Subsequently, a version of this standard became ISO 60601-2-13:2003, which became ISO/IEC 80601-2-13:2011, rewritten under the third edition of the general standard.28

Each of these standards applies the same requirements to both the workstation as a whole and the individual modules. These standards cover environmental condi-tions, electrical shock hazards, mechanical hazards, exces-sive or unwanted radiation, and excessive temperature; they also set requirements for construction as well as for minimum accuracy. Although these standards recognize the practice standards both in the United States and in other countries, they do expect minimum monitoring configurations. Additionally, they require that certain performance standards be met for those elements that are present.

Hazards inherent in the intended physiologic function of an anesthetic workstation and its individual components

Part 2: Anaesthetic gas scavenging disposal systems ISO 7396-2:2007Terminal units for medical gas pipeline systemsPart 1: Terminal units for use with compressed medical gases and vacuum ISO 9170-1:2008Part 2: Terminal units for anaesthetic gas scavenging systems ISO 9170-2:2008Pressure regulators for use with medical gasesPart 1: Pressure regulators and pressure regulators with flow-metering devices ISO 10524-1:2006Part 2: Manifold and line pressure regulators ISO 10524-2:2005Part 3: Pressure regulators integrated with cylinder valves ISO 10524-3:2005Part 4: Low-pressure regulators ISO 10524-4:2008Anaesthetic and respiratory equipment: Compatibility with oxygen ISO 15001:2010Flow-metering devices for connection to terminal units of medical gas pipeline systems ISO 15002:2008Oxygen concentrator supply systems for use with medical gas pipeline systems ISO 10083:2006High-pressure flexible connections for use with medical gas systems ISO 21969:2009Rail systems for supporting medical equipment ISO 19054:2005Medical gas systems: Systems for evacuation of plume generated by medical devices ISO/WD 16571

From http://www.iso.org/iso/iso_catalogue/catalogue_tc/catalogue_tc_browse.htm?commid=51986&published=on*Replaces IEC 60601-2-13:2003+A1:2006.Replaces ISO 21647.Amd, amendment; TS, technical specification.3

TABLE 34-7 Selected Published Standards under the

Title

Anaesthetic and respiratory equipment, Conical connectors. PartAnaesthetic and respiratory equipment, Conical connectors. Partbearin g connectors

Anaesthetic machines for use with humansLow-pressure hose assemblies for use with medical gases

Anaesthetic vaporizers: Agent-specific filling systemsInhalational anaesthesia systems. Part 7: Anaesthetic systems fologistical supplies of electricity and anaesthetic gases

Gas mixers for medical use: Stand-alone gas mixersInhalational anaesthesia systems: Draw-over vaporizers and assoMedical electrical equipment. Part 2-13: Particular requirements performance of an anaesthetic workstation

Medical electrical equipment. Part 2-55: Particular requirements performance of respiratory gas monitors

Medical supply unitsMedical gas pipeline systemsPart 1: Pipeline systems for compressed medical gases and vacu4 StandardS and regulatory ConSiderationS 709

Responsibility of ISO TC 121 SC/1 and SC/6

Standard

1: Cones and sockets ISO 5356-1:2004 2: Screw-threaded weight- ISO 5356-2:2006

ISO 5358:1992ISO 5359:2008,Amd 1:2011ISO 5360:2012

r use in areas with limited ISO 8835-7:2011

ISO 11195:1995ciated equipment ISO/TS 18835:2004for basic safety