Medical Devices and the Public's Health The FDA 510(k) Clearance Process at 35 Years (2011) / Chapter Skim
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3 Components of US Medical-Device Regulation
3 Components of US Medical-Device Regulation
Pages 41-84
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From page 41... ...
clearance process. TOOLS AND AUTHORITIES FOR REGULATING MARKETED DEVICES In general, medical-device regulation is described by following the typical life cycle of a device, starting with research and development, progressing to premarket review by the Food and Drug Administration (FDA)
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to assure, through a quality review process, that marketed devices, subject to general and applicable special controls, provide a reasonable assurance of safety and effective ness; and (2) to foster innovation.
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There are special requirements for those who reprocess single-use medical devices. Section 502(v)
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44 MEDICAL DEVICES AND THE PUBLIC'S HEALTH name and all places of business.10 Any additional place of business must be registered immediately.11 Registration is also required for establishments outside the United States where devices are made for importation into the United States.12 Registration is to be electronic.13 Listing of Products Each registered person must file with the FDA a list identifying each device made or processed for commercial distribution in the United States.14 The label and labeling15 for each listed device and a representative sample of other labeling must be provided.16 The FDA may request a registrant to provide a statement as to why it believes that any product listed is not subject to a performance standard or a premarket approval (PMA) application requirement.17 If a device previously listed is no longer made, the registrant must provide a notice of discontinuance regarding the product.18 Listings are to be electronic.19 Label Information The label is affixed to the device or its immediate container.20 The label of a device must prominently disclose the company name, trade name, or trade symbol of the original manufacturer.21 It must also disclose the name and place of business of the manufacturer, packager, or distributor and the quantity of contents in the package.22 The device must be identified by its established or common nonproprietary name (if any)
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. 26Prescriptiondevices are not the same as restricted devices, although an individual device may be both.
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Controls Applicable Only to Higher-Risk Devices Restricted Devices If the FDA determines that a device's potential for harm or collateral measures necessary for its use are such that there cannot be reasonable assurance of its safety and effectiveness without the restriction, the agency is authorized to require that the device be restricted to sale, distribution, or use, only on the written or oral authorization of a healthcare practitioner or "upon such other conditions as [the FDA] may prescribe."39 The statute goes on to suggest both the types of other conditions that the FDA might consider and limitations of these conditions if used: No condition .
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,42 or as a condition for the approval of a PMA application (usable only for Class III devices) .43 Although the language is quite similar to that used by the FDA to determine whether a device should be a prescription device,44 the designations as "restricted device" and "prescription device" are technically distinct.
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During inspections of manufacturing plants, the FDA is I authorized by one provision of the statute to see the production and distribution records related to restricted devices but not to devices that are not restricted.50 A separate provision, however, empowers the FDA to inspect any records that are required by law to be kept.51 The agency has directed that specific production and distribution records on all devices be kept as part of good manufacturing practice requirements.52 Thus, the failure to designate devices as restricted has not adversely affected the FDA's ability to examine manufacturing records. Controls Related Only to Class II or Class III Device Tracking The FDA may require a manufacturer to adopt a method for tracking a Class II or Class III device whose failure might be reasonably likely to have serious adverse health consequences, that is intended to be implanted for more than 1 year, or that is a life-sustaining or a life-supporting device 48FFDCA § 502(q)
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The agency has issued regulations creating the general requirements for complying with this provision.55 The authority to impose tracking requirements is discretionary with the FDA and is exercised by an "order" to individual manufacturers covering each affected device.56 Postmarket Surveillance The FDA may require a manufacturer to conduct surveillance of a Class II or Class III device that meets any of the criteria for device tracking (above) or is expected to have substantial use in pediatric populations.57 "Postmarket surveillance" is a specific activity defined by the statute and is not to be confused with "postmarketing surveillance," which encompasses a wide array of programs, including adverse-event reporting by manufacturers and user facilities, third-party safety monitoring, and FDA–academic collaborations.
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. In parallel, the definition of Class III covers devices that cannot be classified as Class I because general controls are insufficient to ensure safety and effectiveness and that cannot be classified as Class II because "insufficient information exists to determine that the special controls .
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First, as noted above, only about 15% of all Class II device types are subject to special controls. Second, some premarket special controls are focused on a particular aspect of the device, such as medical devices that include an antimicrobial agent, or on generic procedures for conducting research for a class of devices, such as animal studies for cardiovascular 66FFDCA § 514(b)
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Fourth, some special controls, such as postmarket surveillance and device tracking, are postmarket forms of regulation that are based on the recognition that the premarket data on safety and effectiveness on some Class II devices may not identify long-term risks or rare events. Finally, practical considerations probably preclude the issuance of special controls for each component of every Class II device.
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in which to look for risks posed by medical devices. Information Provided by Third Parties • evice-related adverse events at device-user facilities.
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Judicial Enforcement Powers The statute provides three remedies or sanctions that can be imposed, but only by order of a federal court, when the FDA finds a product or a manufacturer not in compliance with the law. To obtain such orders, the FDA must work through the DOJ Office of Consumer Litigation and the US attorney's offices around the United States.
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and win a judgment or verdict. To get a judicial action brought, CDRH must first prepare the case and then persuade the FDA associate commissioner for regulatory affairs (and the Office of Enforcement)
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administrative proceedings, including formal or informal hearings -- to accomplish specific tasks. Most of the authorities apply a criterion related to the risks posed by the device in question; the criteria are quite similar but not identical throughout the authorizing language.
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to cease distribution of the device immediately and to instruct healthcare professionals and device-user facilities (for example, hospitals and ambulatory surgical centers) to cease use of the device.90 After issuance of the order, the FDA must provide an opportunity for an informal hearing, which must consider both the merits of the order and whether the device should be physically recalled; the FDA is to vacate the order if the grounds for the action prove inadequate.91 After the hearing (if any)
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has violated any requirement of the FFDCA related to a medical device, it may impose a civil money penalty in an amount not exceeding $15,000 for each violation and not exceeding $1 million for all violations adjudicated in a single proceeding.95 Exceptions are made for some technical violations, such as a violation of good manufacturing requirements that involves devices that 93FFDCA § 518(a)
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The detention period is to permit the FDA to decide whether to initiate a seizure action or undertake other actions. The manufacturer is entitled to a prompt informal hearing on any detention order.98 The FDA does not track the numbers of detention orders that precede seizure.
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Because CDRH has referred in its preliminary report to "important limitations" of its postmarket controls, it is appropriate to examine what each of the procedures entails. Notice-and-Comment Rule-Making The Administrative Procedure Act provides that regulations generally may be issued only after notice of the proposed rule is provided to interested persons and they are given an opportunity to comment before the rule is made final.101 The FDA has adopted detailed procedures for promulgating regulations.102 This can lead to improvements in the program or the development of an alternative.
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In many situations, a private party who loses a decision after a formal evidentiary hearing may seek review by a federal court. Informal Hearing The FDA has established procedures for a "regulatory hearing" to provide an expeditious opportunity for an adversely affected party to be heard on a proposed or actual order.107 In contrast with a formal hearing, the rules of evidence do not apply.
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COMPARISON OF THE FOOD AND DRUG ADMINISTRATION'S AUTHORITIES OVER MARKETED DRUGS AND MARKETED DEVICES In contrast with the system designed for medical devices, the FDA's drug regulatory framework after the Drug Amendments of 1962 required a more standardized, clinical-trial–based premarket review of both safety and effectiveness of all new drugs and placed less emphasis on postmarket surveillance and management of risks.108 Until passage of the Food and Drug Administration Amendments Act of 2007 (FDAAA) ,109 it could be fairly said that the FDA had better risk-management authorities for marketed devices than it had for approved drugs.
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This procedural complexity may have contributed to CDRH's stated concern about limitations on its statutory authorities, and it tends to increase the effect of FDA's resource constraints. Authority to Gather Evidence During the Postmarket Period Table 3-1 compares the FDA's authorities to obtain information regarding risks posed by drugs and medical devices after they enter the marketplace.
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. The FDAAA also directed the agency to prepare an analysis of adverseevent reports for each newly approved drug within 18 months after approval or after use by 10,000 people, whichever is later.111 Authority to Take Action to Manage Emerging Safety Issues The FDA has several authorities that allow it to manage safety issues as they occur.
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In contrast, the FDAAA substantially expanded the FDA's authority to require mandatory safety-related labeling changes for already-approved drugs at any point in their life cycle.112 The process calls for the FDA to notify manufacturers of new safety information that the agency believes should be placed in the drug's labeling. There are brief periods for response (30 days)
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of risk Restricting distribution Discretion to restrict by Discretion to restrict under REMS plane or use restricted-device powers Compelling special Discretion to compel by Discretion to compel through labeling for patients REMS plan or MedGuide special controls (by notice programf and-comment rule-making regarding Class II device) or premarket approval (as condition of approval for Class III)
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67 COMPONENTS OF US MEDICAL-DEVICE REGULATION TABLE 3-2 Continued FDA Authority Approved Drugs Marketed Devices Imposing civil money No authority (other Discretionary authority to penalties for violations than for false direct-to- impose after formal hearing consumer advertising of prescription drugs) g Detaining product in No authority to order Authority to detain upon anticipation of seizure order Detaining and denying Discretionary authority Discretionary authority products offered for identical for drugs and identical for drugs and devices import devices Communicating risk– Required for drug No explicit communication productsh benefit information on program or process, but the marketed products in FDA has general authority timely fashion to issue public-health notificationsi aFFDCA § 505(e)
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The 1976 Medical Devices Amendments (MDA) adopted a three-tier system to determine the need for additional regulatory controls, in the form of premarket review, to protect and promote public health.
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may require.124 The statute does not give the FDA authority to waive any of those requirements, but the FDA permits an applicant to omit information that is not applicable to the device if the omission can be justified.125 In 2002 and again in 2007, Congress enacted 5-year user-fee programs under which persons submitting PMA applications and 510(k) submissions must pay a fee to underwrite some of the cost of FDA review.
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Thus, the obligations of the PMA application process extend well past the initial review and approval. User fees for PMA supplements in FY 2011 range from $3,800 to $236,000, depending on the type of supplement and hence the FDA resources needed to review it.
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. The same legislation that established user fees for PMA applications required fees for the review of 510(k)
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submission does not include much of the information required in a PMA application, the time needed for preparation of the TABLE 3-3 Summary of Key Differences Between PMA Applications and 510(k) Submissions Premarket Approval Application 510(k)
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. Determining the "value added" to device safety and effectiveness by requiring a PMA application, as opposed to a 510(k)
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funded by user fees increased by 113% from 1999 (856 FTEs)
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submissions has risen dramatically, from 166 in 2003 to 249 in 2009. The number of FTEs dedicated to processing PMA applications has grown from 133 to 152 in the same period (Desjardins, 2011)
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The FDA supervisory official is expected to review the third-party submission and make a decision on the submission within 30 days of receipt. GAO found that often the third-party review could be faster than FDA review for traditional 510(k)
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Information-Sharing and Technology Inadequacies in information-sharing and technology in the FDA are felt at all levels and centers in the agency. In 2007, the FDA produced a strategic action plan that focused on four strategic goals: strengthening the FDA, improving the safety of patients and consumers, increasing access to new medical and food products, and improving the safety and quality of manufactured products and the supply chain (FDA, 2007a)
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single comprehensive tracking warehouse accessible to all staff and the pilot testing and evaluation of a Web-based tracking system for premarket review of medical devices (GAO, 2009d)
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For example, the iReview program, a pilot application begun in 2008, automated the premarket certification of medical devices. The iReview system is a workflow-management tool intended to automate the end-to-end 510(k)
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process, not on the scientific validity of the review decisions.143 CDRH has long required device manufacturers to operate a qual ity system.144 In an oversimplified description, the regulations prescribe a continuous-improvement process in which specifications and operating procedures are established, persons who have appropriate backgrounds 141Memorandum Re: Medical Device Hearing, May 4, 1987, Medical Devices and Drug Issues: Hearing Before the Subcomm. on Health and the Env't of the H
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Those basic principles are as applicable to the making of 510(k) clearance decisions -- and any other regulatory decisions (such as PMA application approvals and the use of postmarketing tools to address emerging safety concerns)
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• inding 3-3 The 510(k) clearance pathway is generally more eco F nomical, faster, and less burdensome to industry and the Food and Drug Administration than the premarket approval application route and has substantially fewer postmarketing controls.
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Senate. Medical devices: FDA's premarket review and postmarket safety efforts (GAO-11-556T)
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2007. Third party review of medical device premarket notifications.
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