Medical Devices and the Public's Health The FDA 510(k) Clearance Process at 35 Years (2011) / Chapter Skim
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Appendix A: History of Medical-Device Legislation and Regulation in the United States
Appendix A: History of Medical-Device Legislation and Regulation in the United States
Pages 207-278
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system and how it evolved to its present state, this appendix outlines pertinent elements in the history of device regulation as they are related to Class II devices generally and to the 510(k) clearance process in particular.
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review. Most Class III devices are subject to FDA review through the premarket approval (PMA)
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To guarantee that the will of Congress would not be subverted by the executive branch, Congress set forth detailed instructions on how the FDA should carry out the law. The original Medical Device Amendments of 1976 more than doubled the length of the FFDCA as it stood at that time.
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decisions become embedded and must be perpetuated. • hether the FDA has appropriately used its authority to establish W performance standards or special controls over Class II devices.
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The focus here is on what Congress has perceived and has done concerning the goals and implementation of the FDA's regulation of medical devices. DEVICE REGULATION UNDER THE 1938 FEDERAL FOOD, DRUG, AND COSMETIC ACT The Pure Food and Drug Act of 1906 did not cover medical devices.
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94-853, at 7-8 (1976) (House Report on the Medical Device Amendments of 1976)
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chaired a study group to consider how to approach new legislation; the group issued its report in September 1970. Among its recommendations were better differentiation of devices and drugs in federal law with the adoption of a new and distinct regulatory regime for medical devices, preclearance review of some devices with the extent of premarket review depending on the novelty and potential hazards of the devices, and expansion of the FDA's nonpreclearance authority over medical devices.
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In that respect, the MDA departed from the approach taken for drugs in 1962, which put extraordinary emphasis on the FDA premarket approval process as the primary means of protecting consumers. For devices, the "gatekeeper" function of premarket approval provided an additional layer of protection but only for a small array of products (Class III)
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intended to affect the structure of any function of the body of 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 animals and which is not dependent upon being metabolized for the achievement of any of its principal intended purposes.19 General Controls The MDA established requirements for industry and authorities for the FDA that would apply to all medical devices. Those provisions are usually described as the general controls and include the following:20 • pplying to all devices the "adulteration" provisions of the 1938 A Act, including -- o prohibiting potential or actual contamination of the product;21 and o requiring adherence to good manufacturing practice regulations promulgated by the FDA.22 • pplying to all devices the "misbranding" provisions of the 1938 A Act, including -- o prohibiting any false or misleading statements in labeling,23 19FFDCA § 201(h)
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upon such other conditions as the FDA may prescribe, if -- because of the potential for harm or the collateral measures necessary to its use -- the FDA determines that there cannot otherwise be reasonable assurance of the safety and effectiveness of the device (devices so designated are called "restricted devices") .26 rohibiting false or misleading advertising of a "restricted device."27 • P • M andating disclosures in all advertising for "restricted devices" of a brief statement of intended uses and relevant warnings.28 • R equiring registration with the FDA by all manufacturers of medical devices.29 • M andating listing with the FDA by a registered firm of all devices it currently markets.30 • R equiring notification to the FDA of any new device proposed to be marketed by a registered firm, at least 90 days prior to introduction for commercial distribution [this is the provision that gave rise to the 510(k)
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.37 • uthorizing the FDA to order detention of a device for up to 20 days, A if the agency believes it is adulterated or misbranded, to permit the preparation and filing of a court action for seizure of the product.38 It must be emphasized that the foregoing requirements and authorities were established in 1976 almost always without regard to the assignment of a medical device into Class I, Class II, or Class III (the classes are defined below)
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and does not present an unreasonable risk of illness or injury.40 A Class II device is one that cannot be classified into Class I (because the general controls are not sufficient by themselves to provide reasonable assurance of safety and effectiveness) but on which there is sufficient information to establish a performance standard or other special controls to provide reasonable assurance.41 A performance standard might include provisions regarding the construction, components, ingredients, and properties of the device and its comparability with power systems; provisions for the testing of the device to ensure conformity to the standard; provisions for measurement of performance characteristics of the device; provisions making the device a "restricted device"; and special labeling requirements related to the installation, maintenance, operation, and use of the device.42 The statute was ambiguous as to whether performance standards were required (that is, necessary to provide reasonable assurance of safety and effectiveness that could not be provided by general controls alone)
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.44 The MDA directed the FDA to classify all then-marketed medical devices (so-called preamendment devices) into one of the three classes on the basis of the criteria just outlined.45 The 1976 Amendments also provided mechanisms for the FDA to reclassify devices originally placed in Class III into lower classes when premarket review was no longer needed to ensure the safety and effectiveness of the device type.46 In addition, the MDA provided that devices that were not on the market when the bill became law (so-called postamendment devices)
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setting forth the fact that the device was classified in Class II and, if a performance standard had been promulgated, appropriate certification or evidence that the product conformed to the standard.56 Again, the FDA would review the notice and determine whether it agreed. The classification of preamendment devices did not include any evaluation of the safety or effectiveness of the individual medical devices.
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Class II devices needed only limited supplemental review to verify conformity with any established performance standard. Class III devices, the truly novel devices that presented significant risks to health, were the only ones that Congress wanted to undergo premarket FDA scrutiny similar to that of new drugs.57 Transition Problems Congress wanted the new standards of safety and effectiveness to be applied to the Class III devices that were already in the marketplace in 1976.
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The 510(k) notification process was a purely transitional tool for Class III devices, which would end as the PMA requirements were fully implemented.
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An alternative exception provided that the postamendment device would not be in Class III if the FDA, in response to a petition, classified it into Class I or Class II.62 Congress assumed that ultimately postamendment devices would also be classified, on the basis of risk, into the appropriate category. But until then, any new product proposed for marketing after 1976 would be subject to PMA requirements unless it was substantially equivalent to a preamendment device already in Class I or Class II (or not yet classified)
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IMPLEMENTATION OF THE MEDICAL DEVICE AMENDMENTS: LONG-TERM TRENDS Resource Limitations Two overarching factors have affected the FDA's efforts to carry out the MDA. First, the agency never had sufficient resources to fulfill all the congressional directives for medical-device classification and regulation.
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submissions and PMA applications, the number of FTEs increased in FY 2004–FY 2008 from 516 to 618.65 Thus, it appears that only in the past few years, with the adoption of user fees, have the resources committed to premarket reviews increased substantially. Procedural Demands The second fundamental factor affecting implementation was an increase in procedural steps needed for the FDA to take administrative actions.
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–(e) (removed by the Safe Medical Devices Act of 1990, Pub.
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. 80Implementation of the Medical Device Amendments of 1976, 41 Fed.
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More than 80% of postamendment Class III devices had entered the market on the basis of a 510(k) showing substantial equivalence to a preamendment device.89 Moreover, many postamendment devices were being found substantially equivalent to preamendment devices in Class I or Class II notwithstanding substantial technologic changes.
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The manufacturer would then have to submit a PMA or file a petition to reclassify the device into Class I or Class II.91 The PMA was totally new and untested but was perceived as likely to be burdensome for both industry and the FDA in cost and time to prepare and review. The alternative, device reclassification, was one of the processes for which Congress had demanded extensive notice-and-comment rule-making procedures and advisory-committee participation; in addition, a reclassification from Class III to Class II could be conditioned on the completion of additional lengthy procedures to establish a performance standard for the device.92 Both alternatives proved very demanding of FDA resources.
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. Third, the amount of data required to show substantial equivalence varies widely, depending on the device.
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If a product should have been processed by a PMA in the 1980s or 1990s but went through the 510(k) clearance process instead, any substantially equivalent product in 2010 must by law be cleared by the 510(k)
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510(k) Found Not Substantially Submissions Found Not Submissions of Other Submissions of Other Year Submissions Equivalent Substantially Equivalent Disposition or Open Disposition or Open 1989 7,023 108 1.5% 1,657 23.6% 1990 5,835 142 2.4% 1,062 18.2% 1991 5,774 146 2.5% 1,115 19.3% 1992 6,533 202 3.1% 1,419 21.7% 1993 6,310 109 1.7% 1,449 23.0% 1994 6,450 96 1.5% 1,527 23.7% 1995 6,078 71 1.2% 1,218 20.0% 1996 5,316 43 0.8% 1,200 22.6% Total 49,319 917 1.9% 10,647 21.6% SOURCE: Adapted from GAO, 1997b, p.
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c. The agency has not required manufacturers of "old" class III devices to submit premarket approval applications.
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3. As a consequence, the FDA is not equipped and, therefore, is unable to assure the American people that many medical devices currently on the market -- and relied upon to treat disease and to sustain life -- are safe and effective.
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GAO also examined the FDA's information systems and interviewed FDA officials. GAO concluded that the FDA needed a comprehensive information system on the safety of medical devices in the marketplace; that development of performance standards for Class II devices -- numbering more than 1,000 at that point -- would be time-consuming and expensive, likely to become obsolete quickly, and perhaps unnecessary to ensure the safety and effectiveness of devices; that review of preamendment Class III devices would take many years; and that new risky devices in Class II and Class III were not being assessed for safety and effectiveness but only for substantial equivalence to preamendment devices.
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In neither case has FDA de termined the safety and effectiveness of the preenactment devices for which the new device is considered substantially equivalent. For Class III devices, FDA is required to make a safety and effectiveness determination for the preenactment device, but has not done so.
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."110 • he FDA did request new legislation to eliminate what it perceived as T a statutory obligation to promulgate performance standards for every HeaLTH aND THe eNv'T of THe H
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The FDA chief counsel set forth the FDA's view of the law: A device is placed in class II because a determination has been made that the class I general controls are insufficient to provide reasonable assurance of the safety and effectiveness of the device. That determination having been made and the device having been put into class II, you have got an outstanding determination that the controls pro vided under class I are insufficient, and a determination that a performance standard should be set for the device.
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. The legislative history contains little to clarify explicitly this apparent contradiction, so we are left with attempting to reconcile these two statutory provisions.116 HIMA goes on to construct an argument that concludes that although the definition of Class II stated that a performance standard is necessary to provide reasonable assurance of safety and effectiveness, it does not require that this standard be promulgated by the FDA.117 March and September 1984 House Subcommittee on Oversight and Investigations Hearings The Subcommittee on Oversight and Investigations held two hearings focused on device-related adverse-medical-experience reporting and the long delay in the FDA's issuance of regulations to implement the authority conferred in the MDA in 1976.118 The FDA promulgated its MDR regulations, to take effect in 3 months (on December 14, 1984)
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clearance process: • he FDA had used the 510(k) clearance process and its interpretation T of substantial equivalence to avoid putting many products into Class III and the concomitant workload that PMA would necessitate (OTA, 1984, p.
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clearance process on findings of substan tial equivalence to preamendment Class III devices that had yet to undergo PMA review for safety and effectiveness (OTA, 1984, pp.
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More immediately, FDA's Office of Chief Counsel has stated that such "piggybacking" is not authorized by the amendments, and if the practice of piggybacking ceases, more postamendments devices will eventually be placed in Class III, and their manufacturers will have to go through the full premarket approval process or petition FDA for reclassification.
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. 123Memorandum Re: Medical Device Hearing, May 4, 1987, Medical Devices and Drug Issues: Hearing Before the Subcomm.
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August 1988 General Accounting Office Report In response to another request of the chairman of the House Subcommittee on Health and the Environment, GAO undertook a study from 1986 to 1987 and issued a report in August 1988 titled Medical Devices: FDA's 510(k) Operations Could Be Improved (GAO, 1988b)
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. GAO underscored the absence of any performance standards for Class II devices and the high percentage of Class III devices for which PMA reviews of safety and effectiveness had not yet begun.
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. Moreover, GAO observed that because of these implementation problems, devices in class II and class III may be marketed through premarket notification without having to meet the additional requirements appropriate to their classification.
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clearance process and eliminating a requirement for the promulgation of performance standards for Class II devices. "The bill would give FDA discretion to apply one or more ‘special controls' to a given device problem."132 The agency, however, opposed the legislative proposal for user reporting of adverse device-related events as unnecessary and infeasible, stating that the system for manufacturer reporting was preferred by the FDA.133 129Medical Device Safety: Hearings Before the Subcomm.
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system: The primary objective of the premarket notification 510(k) clearance process is to determine whether a new or modified device is "substantially equivalent" to a device already on the market.
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The three most relevant to the present discussion involve the regulatory standards and related requirements that differentiate Class I and Class II devices, the definition of substantial equivalence, and the retrospective review of the safety and effectiveness of preamendment Class III devices. Definition of Class II; Replacement of Mandatory Performance Standards Requirements for All Class II Devices with Discretionary Special Controls Authority Congress recognized both that the FDA had been unable to promulgate performance standards and that performance standards were not necessar 136Id.
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Accordingly, it revised the definition of Class II to read as follows: A device which cannot be classified as a class I device because the general controls by themselves are insufficient to provide reasonable assurance of the safety and effectiveness of the device, and for which there is sufficient information to establish special controls to provide such assurance, includ ing the promulgation of performance standards, postmarket surveillance, patient registries, development and dissemination of guidelines (including guidelines for the submission of clinical data in premarket notification sub missions in accordance with section 510(k)
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many new and novel devices that would have been placed in Class III. For instance, the agency allowed a new device to be determined to be substantially equivalent to a preamendment device, notwithstanding important technologic differences, if the new device was as safe and effective as the antecedent.
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The FDA also permitted a postamendment device to claim substantial equivalence to a preamendment device through an implied string of precedents from other postamendment devices previously cleared by 510(k) review, a process known as piggybacking.
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. the term "substantially equivalent" or "substantial equivalence" means, with respect to a device being compared to a predicate device, that the device has the same intended use as the predicate device and that [FDA]
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The standard for substantial equivalence permitted the agency to use safety and effectiveness data only when a new device offered technologic characteristics that differed from those of the predicate device. Moreover, Congress made clear that it did not believe that a substantial-equivalence determination was a finding of safety or effectiveness.
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submitter to wait for a written response (called an order) from the FDA stating that its product was substantially equivalent before commercializing it.161 Preamendment Class III Devices Both the House and the Senate committees considering the 1990 legislation were displeased by the FDA's lack of progress since 1976 in pro 158H.R.Rep.
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As with the original 1976 law, these controls were applicable under the 1990 amendments without regard to the classification of a device for premarket review purposes. User Reporting of Device Risks A GAO study in 1986 revealed that hospitals often did not report potentially hazardous medical devices to the FDA or the manufacturers.166 Even though manufacturers were required to investigate and report to the FDA information received from hospitals, physicians, patients, and others, the system would fail if users did not report to the manufacturers.
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. to provide information necessary to protect the public health and to provide safety and effectiveness information for the device."170 Device Tracking For any device whose failure would be reasonably likely to have serious health consequences and that was permanently implantable or was a life-sustaining or life-supporting device used outside a "device user facility," the manufacturer was required to adopt a method of device tracking (such as a patient registry)
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immediately to cease distribution of a device, to notify healthcare providers and deviceuser facilities to cease using the device, and to recall the device if there was a reasonable probability that the device would cause serious adverse health consequences or death.177 Civil Money Penalties The FFDCA of 1938, as amended by the MDA of 1976, created a limited array of sanctions to penalize individuals and companies that violated the law: criminal fines and imprisonment and seizure and forfeiture of violative products.178 Those penalties could be imposed only after a trial in federal court, criminal punishments required proof beyond a reasonable doubt, and the threat of imprisonment did not apply to corporations. To enhance the FDA's enforcement credibility, Congress in 1990 provided that the FDA could also impose substantial civil money penalties by an administrative hearing without going to federal court for any violation of the law related to medical devices.
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" also conform to "current good manufacturing practice."182 DEVELOPMENTS IN 1990–1997 The Medical Device Amendments of 1992 The 1990 legislation directed the FDA to promulgate final regulations implementing the authority to require adverse–medical-event reporting by user facilities by May 28, 1992; if not, any proposed regulations would automatically become effective.183 The FDA did not issue proposed regulations until March 27, 1992, so that left only 2 months for public comment and for implementation. Congress elected to extend the effective dates by 6 months (for the regulations)
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at 238-39. 187Memorandum from the principal deputy inspector general to the acting assistant secretary for health, Re: Follow-Up Review on Internal Control Weaknesses in the Food and Drug Administration's Medical Device 510(k)
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The resulting report was critical, observing (albeit on the basis of a small sample of PMA applications and 510(k) submissions containing clinical data)
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The law said that a state could not establish a requirement with respect to a device related to safety or effectiveness of the device that was different from or in addition to those requirements imposed by the FDA law.191 In the product liability suit, the manufacturer argued that imposition of liability by a state court based in tort law had the effect of creating such requirements with respect to design of the device. The device in question was a postamendment Class III product cleared through the 510(k)
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-- based on a determination that the device is substantially equivalent to a pre Amendments Class III device -- does not reflect a determination by the FDA that the device is safe and effective, much less a specific determination that the device's design is required to ensure its safety and effectiveness.
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An opinion, representing the views of all the other justices, concurred that the 510(k) "process merely evaluates whether the Class III device at issue is substantially equivalent" to a preamendment device.195 In sum, the Supreme Court found that the 510(k)
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THE FOOD AND DRUG ADMINISTRATION MODERNIZATION ACT OF 1997 A variety of bills addressing congressional concerns about FDA regulation of foods, drugs, and medical devices were consolidated and passed as the FDA Modernization Act of 1997.198 The device-related provisions modified both premarket and postmarket controls generally in the direction of restricting the FDA's preclearance authorities to accelerate the pace of technology transfer. Modifications Regarding Premarket Review of Devices Congress concluded that the FDA regulatory system was not keeping pace with medical innovation.
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to identify each type of device in Class II for which a 510(k) submission would not be necessary to provide reasonable assurance of safety and effectiveness.
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submission was still required other than Class II devices intended to be permanently implantable or life-sustaining or lifesupporting or for which clinical data are required.205 Evaluation of Automatic Class III Designations The new law required the FDA to evaluate whether a new device that, after submission of a 510(k) notification by the sponsor, was determined to be NSE to another device and therefore was automatically placed in Class III could be classified into Class I or Class II immediately without having to undergo PMA review.206 That process, now called the de novo 510(k)
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(2006) ("the information submitted that the device is substantially equivalent to such other device, including clinical data if required by [FDA]
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Moreover, in making such a request, the FDA has to "consider the least burdensome means of demonstrating substantial equivalence and request information accordingly."210 Device Classification (and Reduction in Scope of PMA Review Regarding Effectiveness) to Consider Substitution of Postmarket Controls The 1997 law directed the FDA to "consider the extent to which reliance on postmarket controls may expedite the classification of devices" into Class I or Class II instead of Class III.211 Congress ordered that "in making a determination of a reasonable assurance of effectiveness" in reviewing a PMA, the FDA must "consider whether the extent of data that otherwise would be required for approval .
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Alternative Procedures for Setting Performance Standards for Class II Devices The 1997 law provided that the FDA could recognize an appropriate performance standard established by a nationally or internationally recognized organization engaged in standard development. In lieu of an extended notice-and-comment rule-making, the FDA could simply issue a notice of recognition.217 In addition, Congress provided a simplified process for applicants to certify compliance with the standard.218 Priority PMA Review for Important New Devices Congress directed the FDA to provide review priority for medical devices that represented breakthrough technologies, for which no approved alternatives existed, that offered substantial advantages over existing ap 215FFDCA § 513(a)
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Limiting Device Tracking to Class II and Class III Devices The 1997 law limited the FDA's authority to require device tracking to Class II or Class III devices whose failure would be reasonably likely to have serious adverse health consequences or that are intended to be implanted for more than 1 year or are life-sustaining or life-supporting and used outside a device-user facility.221 Limiting Postmarket Surveillance Requirements to Class II and Class III Devices Congress also restricted the FDA's power to order postmarket surveillance for devices to those in Class II or Class III whose failure would be reasonably likely to have serious adverse health consequences or that are intended to be implanted for more than 1 year or are life-sustaining or lifesupporting and used outside a device-user facility.222 219FFDCA § 515(d)
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For example, Congress • reated a system whereby people other than federal employees could C be accredited to conduct inspections of manufacturers of Class II and Class III devices.228 • ermitted labeling for prescription devices intended for use in health P 223FFDCA § 519(a)
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. 233Medical Device User Fee Stabilization Act of 2005, Pub.
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Finally, 217 original PMA applications and 784 supplemental PMA applications for Class III devices had been reviewed, of which 78% were approved. As of October 2008, 20 types of Class III devices could still be cleared through the 510(k)
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actions. • hether each type of Class II device must be subject to special con W trols to provide reasonable assurance of the safety and effectiveness of devices of that type.
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The agency later concluded that reviewing PMAs and reclassifying Class III devices were too expensive, as would establishing performance standards have been. The FDA evolved the 510(k)
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2011. 515 program initiative: The 515 program initiative (aka reclassification of pre amendments class III 510(k)
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1984. Federal policies and the medical devices indus try.
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