Draft Guidance for Industry and Food and Drug Administration Staff

Postmarket Surveillance Under Section 522 of the Federal Food, Drug and Cosmetic Act

1. Introduction

Postmarket surveillance under section 522 of the Federal Food, Drug, and Cosmetic Act (the act) is one means by which the Food and Drug Administration (FDA) can obtain additional safety and/or effectiveness data for a device after it has been cleared through the premarket notification (510(k)) process or approved through the premarket approval application (PMA), humanitarian device exemption (HDE), or product development plan (PDP) process, when it is necessary to protect the public health. Postmarket surveillance is not a substitute for obtaining the necessary premarket information to support 510(k) clearance or PMA, HDE, or PDP approval.

Section 307 of the FDA Amendments Act of 2007 (FDAAA) (Pub. L. 110-85) amended section 522 of the act by adding class II and class III devices expected to have significant use in pediatric populations as a category of devices potentially subject to a postmarket surveillance order, authorizing the agency to order postmarket surveillance for durations longer than 36 months and as a condition of clearance or approval for devices within this category, and adding a dispute resolution provision.

This guidance document is intended to assist those subject to section 522 postmarket surveillance imposed by FDA by providing:

an overview of section 522 of the act,

procedural information on how to fulfill 522 obligations ¹, and

recommendations on the format, content, and review of postmarket surveillance study submissions.

Substantive additions to the 2006 version of this guidance document include: (1) guidance regarding the pediatric criterion added by section 307 of FDAAA; (2) recommendations for the content of postmarket surveillance study submissions, consistent with previous FDA requests; (3) descriptions of study status categories that more precisely indicate study progress and the adequacy of the data; and (4) updated procedures based on the transfer of the program area to Division of Epidemiology (DEPI), Office of Surveillance and Biometrics (OSB).

FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.

2. Legal Background

A. Statutory Criteria

Section 522 of the act, 21 U.S.C. 360l, authorizes FDA to require postmarket surveillance in the following instances:

a class II or class III device for which failure of the device would be reasonably likely to have a serious adverse health consequence (Section 522(a)(1)(A)(i) of the act);
a class II or class III device expected to have significant use in pediatric populations (Section 522(a)(1)(A)(ii) of the act);
a class II or class III device intended to be implanted in the human body for more than one year (Section 522(a)(1)(A)(iii)(I) of the act); and
a class II or class III device intended to be a life-sustaining or life-supporting device used outside of a user facility (Section 522(a)(1)(A)(iii)(II) of the act).

One or more of the criteria above need to be met for section 522 postmarket surveillance to be considered by FDA.

B. Considerations Regarding Pediatric Population Provisions

As stated above, FDAAA amended the scope of section 522 postmarket surveillance by authorizing postmarket surveillance for class II and III devices that are â€œexpected to have a significant use in pediatric populations.â€ This provision is not limited to devices labeled for pediatric uses; accordingly, FDA may use this authority to order surveillance of devices expected to have significant off label use in pediatric populations. The new provisions added by FDAAA also authorize the agency to order postmarket surveillance as a condition of clearance or approval for devices expected to have significant pediatric use.

FDAAA also states that any â€œpediatric postmarket surveillance required under section 522â€ is considered to be an â€œapplicable device clinical trialâ€ under section 402(j)(1)(A)(ii) of the Public Health Service Act (PHS Act) (42 USC 282(j)(1)(A)(ii)). As such, the pediatric postmarket surveillance study must be in compliance with the registration and results submission requirements of section 402(j) of the PHS Act (42 USC 282). Additional information on these requirements can be found at http://clinicaltrials.gov/ct2/invest and http://prsinfo.clinicaltrials.gov/.

C. Postmarket Surveillance Study Duration

In general, section 522(b)(1) of the act authorizes FDA to order prospective postmarket surveillance for a duration of up to 36 months unless the manufacturer and FDA agree to extend that timeframe. However, FDAAA added section 522(b)(2) to the act, which authorizes FDA to require a prospective surveillance period of more than 36 months with respect to a device that is expected to have significant use in pediatric populations, if such period is necessary in order to assess the impact of the device on growth and development, or the effects of growth, development, activity level, or other factors on the safety or efficacy of the device. FDA will work with the sponsor to determine the appropriate timeframe for a pediatric study.

2;
subject accountability data stratified by each follow-up timepoint for the entire population and for each subgroup. To limit the potential bias in safety and effectiveness data, you should make every effort to reduce the number of subjects lost-to-follow-up.

if applicable, an explanation for:

subjects lost to follow-up, as well as any measure to minimize such future events

subject and physician-initiated discontinuations

any deaths, including reports from post-mortem examinations

summary of safety and/or effectiveness data and an interpretation of study results to date.

â€œElectronic Copies for Pre-Market Submissionsâ€ QA. Electronic copies of postmarket surveillance submissions accompanying the paper submission should be submitted to the address above.

10. Failure to Complete a Postmarket Surveillance Study

Failure or refusal to comply with a requirement under section 522 is a prohibited act under section 301(q)(1)(C) of the act, 21 U.S.C. 331(q)(1)(C), and renders the device misbranded under section 502(t)(3) of the act, 21 U.S.C. 352(t)(3). Please note that violations of sections 301(q)(1)(C) and 502(t)(3) may lead to enforcement actions including seizure of your product, injunction, prosecution, and/or civil money penalties. See 21 CFR 822.20. Under section 522(c), manufacturer may request review under section 562 of the act, 21 U.S.C. 360bbb-1, of any order or condition requiring postmarket surveillance under section 522.

There may be circumstances that make it impossible or inappropriate for you to complete a particular postmarket surveillance study. For instance, you may have instituted a voluntary withdrawal or recall of the device from the market, thereby negating the need for the study. We recommend that you initiate early communication with FDA if you intend to terminate the study prior to fulfilling the postmarket surveillance study commitment.

Alternatively, if FDA determines the study will not answer or adequately address the questions in the order, for example because of the study design, because of study data inadequacies, or due to a discontinuation in marketing or manufacturing of the device, but the study objectives remain important, we may initiate termination of the original study and discuss establishing a new postmarket surveillance study commitment and schedule.

11. Public Disclosure of a Postmarket Surveillance Study

After approval of your plan, the contents of the original submission and any amendments, supplements or reports may be disclosed in accordance with the Freedom of Information Act. We will continue to protect trade secret and commercial confidential information, as well as any personal privacy information for patients. 21 CFR 822.23.

Any postmarket surveillance study that is an â€œapplicable device clinical trialâ€ as defined in section 402(j)(1)(A)(ii) of the PHS Act (42 USC 282(j)(1)(A)(ii)), added by Title VIII, FDAAA, must comply with registration and results submission requirements for such clinical trials. Certain information on clinical trials is publicly available on the www.ClinicalTrials.gov website. Additional information on these requirements can be found at http://clinicaltrials.gov/ct2/invest and http://prsinfo.clinicaltrials.gov/.

In addition, to increase transparency to our stakeholders, including consumers, physicians, and industry, FDA posts information about postmarket surveillance studies on our 522 webpage. This information is posted in compliance with applicable disclosure statutes and regulations. Study details that may be posted include:

postmarket surveillance study number
applicant name
device name
medical specialty (e.g., cardiovascular, orthopedic)
date of the 522 order
study name
plan approval date
study population
study status
interim and final report schedule
due date for interim and final report (based on agreed-upon schedule)
FDA receipt date of interim and final report
status category of interim and final report.

Additional study elements may be posted on FDAâ€™s website, as permitted by applicable disclosure statutes and regulations.

¹ Refer to 21 CFR part 822 for the full set of postmarket surveillance regulations. This guidance document focuses on only some of the procedural regulations.

² If a change in the study milestones/timeline could significantly impact the outcome of the postmarket surveillance study, then you should submit that revision as part of a 522 supplement for review and approval.

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Draft Guidance for Industry and Food and Drug Administration Staff

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