You should submit comments and suggestions regarding this draft document within 90 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.regulations.gov . Identify all comments with the docket number listed in the notice of availability that publishes in the Federal Register.
For questions regarding this document, contact Mary Beth Ritchey at 301-796-6638 or via email at MaryElizabeth.Ritchey@fda.hhs.gov .
When final, this document will supersede “Guidance for Industry and FDA Staff; Postmarket Surveillance Under Section 522 of the Federal Food, Drug, and Cosmetic Act” issued on April 27, 2006
Additional copies are available from the Internet. You may also send an e-mail request to email@example.com to receive an electronic copy of the guidance or send a fax request to 301-827-8149 to receive a hard copy. Please use the document number 1754 to identify the guidance you are requesting.
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:
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.
A. Statutory Criteria
Section 522 of the act, 21 U.S.C. 360l, authorizes FDA to require postmarket surveillance in the following instances:
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 “expected to have a significant use in pediatric populations.” 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 “pediatric postmarket surveillance required under section 522” is considered to be an “applicable device clinical trial” 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.
A. Identification of Issue
CDRH staff may identify device issues that are appropriate for studying in a postmarket surveillance study at any point during the life cycle of the device. Such issues may be identified through a variety of sources including analysis of adverse event reports, a recall or corrective action, post-approval study data, review of premarket data, reports from other governmental authorities, or review of scientific literature.
Examples of situations that may raise postmarket questions, during both the premarket and postmarket periods, are listed below.
B. Team Review of Issue
The device issue identified in Section 3A above is brought to the 522 Team Lead who then establishes a cross-Center team (i.e., pre-522 team) to review the issue in more depth. The pre-522 team discusses numerous elements with the ultimate goal of making a recommendation to the DEPI Division Director and OSB Director as to whether or not a 522 order should be issued to address a public health question.
Some of the elements discussed by the pre-522 team include:
C. Issuance of 522 Order
An order for postmarket surveillance under section 522 will generally be issued by the OSB Director. The 522 order will identify the premarket submission(s) involved (i.e., 510(k), PMA, PDP, or HDE), the public health question(s), the rationale for the 522 order, and study design recommendations to assist you in preparing the postmarket surveillance plan. 21 CFR 822.5.
You must submit your postmarket surveillance plan within 30 days of receipt of the 522 order. 21 CFR 822.8.
Postmarket surveillance study plans are reviewed as an original submission and its amendments until the plan is approved. Subsequent changes to the plan after its approval are submitted and reviewed as postmarket surveillance study supplements. FDA will review all postmarket surveillance submissions and respond within 60 calendar days. 21 CFR 822.17.
A. Elements to Include in a Postmarket Surveillance Study Plan
The general and specific content for a postmarket surveillance study plan is outlined in 21 CFR 822.9 and 822.10. For clarity purposes, FDA describes the elements to include in a postmarket surveillance study plan in more detail as follows:
B. FDA and Sponsor Agreement on Study Plan
FDA will evaluate the proposed study plan to determine whether it is administratively complete and whether the surveillance plan will result in the collection of useful data that will answer the surveillance question(s). 21 CFR 822.16. FDA will then issue an approval order, an approvable letter requesting specific revisions or additional information needed before the plan can be approved, or a letter disapproving the proposed plan and explaining the reasons for disapproval. 21 CFR 822.19
If you disagree with FDA about the content of the plan or if we disapprove your plan, possible recourse options are described in 21 CFR 822.22. These include requesting a meeting with the Director, OSB; seeking internal review of FDA’s decision under 21 CFR 10.75; requesting an informal hearing under 21 CFR Part 16; or requesting review by the Medical Devices Dispute Resolution Panel of the Medical Devices Advisory Committee.
FDA developed this guidance document to help facilitate timely discussions with sponsors on postmarket surveillance study issues and challenges. We believe that early and ongoing interactions will afford optimal opportunities to agree on plans or other study issues and will be the primary method for resolving any issues. However, if you do not have an approved study plan within 6 months of issuance of the 522 order, the study status will be categorized as “Plan Overdue” on FDA’s website. If you fail to meet the requirements for obtaining study plan approval within 12 months of the date of the 522 order, FDA will generally consider this to be a failure to comply with a requirement under section 522, which would render the device misbranded under section 502(t)(3) of the act.
C. Changes to an Approved Postmarket Surveillance Study Plan
If you wish to propose a change to an approved postmarket surveillance study plan, you must submit your request and the revised study plan for FDA review and approval. 21 CFR 822.21. Any submission involving a change to the approved study plan is tracked by FDA as a supplement to your 522 study.
D. Types of Postmarket Surveillance
We may order postmarket surveillance to address a wide variety of device-related public health questions. The table below describes different types of postmarket surveillance that may be used to address the public health question.
An Interim Postmarket Surveillance Study Report is a written report to FDA on the status of the postmarket surveillance study prior to its completion.
A. Submission of Interim Postmarket Surveillance Study Report
21 CFR 822.38 requires that you submit interim and final reports as specified in your approved postmarket surveillance plan. Unless otherwise specified in the 522 order, we recommend you submit an Interim Postmarket Surveillance Study Status Report every 6 months for the first 2 years of the study and annually, thereafter, from the date of the 522 study plan approval or other negotiated starting date. We recommend you continue this reporting schedule until you have submitted the Final Postmarket Surveillance Study Report. We also recommend you indicate the appropriate time span on the interim report cover in bold letters (e.g., 6-Month Interim Postmarket Surveillance Study Report, 12-Month Interim Postmarket Surveillance Study Report). FDA intends to complete the review of your interim report and respond within 60 calendar days.
B. Sponsor’s Reporting Status
Upon receipt of the interim report, FDA will determine your reporting status based on the agreed-upon schedule in the postmarket surveillance study plan. The reporting status categories appear in the table below.
C. Evaluation of Interim Postmarket Surveillance Study Status Report
FDA epidemiologists from OSB intend to evaluate the Interim Postmarket Surveillance Study Report based on a wide range of criteria, including:
OSB will consult with ODE or OIVD and other offices as needed to ensure the data are assessed appropriately.
If we have questions regarding the data provided in the report, or if we believe the data are incomplete or insufficient, we may request additional information through the interactive review process and/or through a deficiency letter.
A Final Postmarket Surveillance Study Report is a written report of a terminated study or a completed postmarket surveillance study.
A. Submission of Final Postmarket Surveillance Study Report
We recommend the Final Postmarket Surveillance Study Report be submitted no later than three months after study completion, and should be prominently identified with Final Postmarket Surveillance Study Report at the top of the cover letter. We also recommend you identify the public health question(s) for which the report is being submitted if more than one study was used to address a particular 522 order. FDA intends to complete the review of your final report and respond within 90 calendar days.
B. Sponsor’s Reporting Status
As with an interim report, upon receipt of the final report, FDA will determine your reporting status based on the agreed-upon schedule in the postmarket surveillance study plan.
C. Evaluation of Final Postmarket Surveillance Study Report
FDA recommends the Final Postmarket Surveillance Study Report describe the study methodology and results and explain how the study fulfills the 522 order. FDA epidemiologists from OSB will review the Final Postmarket Surveillance Study Report and determine if you have satisfied the 522 order. OSB will consult with ODE or OIVD and other offices as needed to ensure the data are assessed appropriately
If we conclude you have fulfilled your 522 obligations, FDA will send you a letter reflecting that decision.
However, if the results of the postmarket surveillance raise new issues or questions, additional actions may be required. We may, for example:
FDA’s ability to adequately track and evaluate postmarket surveillance studies depends on the quality and timeliness of information you provide. The recommendations in this section are intended to ensure the reports you submit contain adequate information for us to identify the product being studied, the specific study being conducted, the status of that study, and, if applicable, the reasons for any delays or failures to complete the study.
FDA recommends that Postmarket Surveillance Study Reports (interim and final) include the information listed below, clearly identified and in separate sections.
A. General Information
FDA recommends this section contain:
B. Submission Information
FDA recommends this section contain:
C. Study Information
FDA recommends this section contain (as applicable):
After the review of a 522 submission, FDA will determine the status of the study using the categories in the table below.
You should send three copies (one electronic and two paper copies) of all postmarket surveillance study submissions to:
As we have explained in other contexts, “An electronic copy is an exact duplicate of a paper submission, created and submitted on a CD or DVD, accompanied by a copy of the signed cover letter and the complete original paper submission. An electronic copy is not an electronic submission.” See “Electronic Copies for Pre-Market Submissions” Q&A . Electronic copies of postmarket surveillance submissions accompanying the paper submission should be submitted to the address above.
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.
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 “applicable device clinical trial” 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:
Additional study elements may be posted on FDA’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.