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Today’s Topic: 

Postmarket Mandated Studies Programs: Overview and Final Guidance 

Updates

December 6, 2022
Postmarket Mandated Studies Programs: 

Overview and Final Guidance Updates

Erika Avila Tang, PhD, MHS

Epidemiologist

Division of Clinical Evidence and Analysis 1 

(Clinical Policy and Quality) 

Office of Clinical Evidence and Analysis

Office of Product Evaluation and Quality

Center for Devices and Radiological Health

U.S. Food and Drug Administration
Final Guidance Documents

3

www.fda.gov/regulatory-information/search-fdaguidance-documents/procedures-handling-postapproval-studies-imposed-pma-orderwww.fda.gov/regulatory-information/search-fdaguidance-documents/postmarket-surveillance-undersection-522-federal-food-drug-and-cosmetic-act
Learning Objectives

• Provide background information on the Postmarket 

Mandated Studies Programs

• Discuss major stakeholder comments on the draft Post- Approval Studies (PAS) and Postmarket Surveillance (522 

studies) guidance documents

• Outline the purpose and scope of the PAS and 522 studies 

final guidance documents

• Identify updates included in the PAS and 522 studies final 

guidance documents

4
BACKGROUND

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Medical Device Safety

“[Our goal for safety is] ...ensuring 

that the FDA is consistently first 

among the world’s regulatory 

agencies to identify and act upon 

safety signals related to medical 

devices...”

6

Statement from FDA Commissioner Scott Gottlieb, M.D. 

and Jeff Shuren, M.D., November 2018
Overall Goal

7

Recommendations on the format, content, and 

review of PAS and 522 submissions

Clear sponsor expectations for study timelines

Timely FDA review of postmarket information
Guidance Timeline

8

Draft PAS/522 

Guidances

Drafts published

May 27, 2021

Final guidances issued 

October 7, 2022

PAS/522 

Guidance Webinar

December 6, 2022

Public comments received 

(July 26, 2021), incorporated 

into final guidance

GO 
Postmarket Mandated Studies Programs Overview

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Protocol 

Approval

PAS Need 

Identified 

Pre-522 

Screener 

Plan

Approval 522 Order 

Interim 

Reports

Approval Order 

with PAS CoA 

Examples of Actions: 

 Posting Final Results on Public Webpage

 Labeling Update

 FDA Communication

PAS Program 

Section 522 Program

Final 

Report

Study Description 

Posted in Public 

PAS/522 Webpage 

Interim webpage updates

 Progress Status

 Performance Updates

Postmarket 

Requirement 

Addressed

PAS Outline

PAS Protocol
STAKEHOLDER COMMENTS ON DRAFT 

GUIDANCES DOCUMENTS

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Stakeholder Comments

Timelines

• Enrollment milestones are too prescriptive and depend on the 

study design

– These are recommended enrollment milestones based on FDA’s 

experience with mandated studies 

• The timeline for sponsor submission of protocols/plans and final 

reports is insufficient

– The recommended timeline to submit final reports is consistent with 

previous guidance document(s) 

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• Web posting of interim results could result in release of confidential 

information and misinterpretation of results 

– FDA generally considers the information to be posted on the website to be publicly 

releasable in accordance with applicable disclosure laws, such as the Freedom of 

Information Act

– When sharing information appropriate to protect public health, FDA will consider the 

benefits of sharing the information, as well as other considerations on the study 

conduct

• Sponsors requested an opportunity to review information before it is posted

– Sponsors will have the opportunity to propose summary data for the website in 

reports

12

Stakeholder Comments

Transparency
PURPOSE AND SCOPE

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Procedures for Handling Post-Approval 

Studies Imposed by Premarket 

Approval Application Order

14

www.fda.gov/regulatory-information/search-fda-guidance-documents/procedureshandling-post-approval-studies-imposed-pma-order
PAS Regulatory Authority

• Class III devices

• Section 513(a)(3)(C) of the FD&C Act

– FDA may consider whether postmarket data collection or other 

conditions might be structured to permit approval subject to those 

conditions

• 21 CFR 814.82(a)(2) for PMAs

– Post-Approval studies can be imposed at time of approval to continue 

evaluation and reporting on the safety, effectiveness, and reliability of 

the device for its intended use

15
PAS Rationale

• FDA may consider it acceptable to collect certain data 

in the postmarket setting, rather than premarket 

under certain circumstances when FDA has 

uncertainty regarding certain benefits or risks of the 

device, but the degree of uncertainty is acceptable in 

the context of the overall benefit-risk profile of the 

device at the time of premarket approval.

16

See FDA guidance documents entitled “Balancing Premarket and Postmarket Data Collection for Devices Subject to Premarket 

Approval” and “Consideration of Uncertainty in Making Benefit-Risk Determinations in Medical Device Premarket Approvals, De 

Novo Classifications, and Humanitarian Device Exemptions.”
PAS Guidance Structure

I. Introduction

II. Background

III. PAS Requirements in PMA Approval Order

IV. PAS Protocols

V. When and How to Submit PAS Reports

VI. Content and Format of Interim and Final PAS Reports

VII. Evaluation of Interim PAS Reports

VIII. Evaluation of Final PAS Reports

IX. Sponsor’s Reporting Status

X. Study Status

XI. Failure to Complete a PAS Requirement

XII. Public Disclosure of PAS Information

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Postmarket Surveillance Under Section 

522 of the Federal Food, Drug, and 

Cosmetic Act

18

www.fda.gov/regulatory-information/search-fda-guidance-documents/postmarketsurveillance-under-section-522-federal-food-drug-and-cosmetic-act
522 Regulatory Authority

• Class II and III devices

• Section 522 of the FD&C Act

– [FDA] may, by order, at the time of approval or clearance of a device or at any 

time thereafter, require a manufacturer to conduct postmarket surveillance... 

for a prospective surveillance of up to 36 months*

– Surveillance must commence within 15 months of the order

• 21 CFR 822 Postmarket Surveillance

– “The purpose of this part is to implement our postmarket surveillance 

authority to maximize the likelihood that postmarket surveillance plans will 

result in the collection of useful data. These data can reveal unforeseen 

adverse events, the actual rate of anticipated adverse events, or other 

information necessary to protect the public health.” (See 21 CFR 822.2)

*Can be longer for devices with expected significant use in pediatrics 19
522 Statutory Criteria

Section 522 of the FD&C Act permits FDA to require 

postmarket surveillance for class II or III devices that meet any 

of the statutory criteria:

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Section 522 of the FD&C Act Criteria

Criterion 1 Failure of the device would be reasonably likely to have a serious adverse 

health consequence.

Criterion 2 Expected to have significant use in pediatric populations.

Criterion 3 Intended to be implanted in the body for more than one year.

Criterion 4 Intended to be a life-sustaining or life-supporting device used outside of a 

device user facility.
522 Guidance Structure

I. Introduction

II. Pre-522 Postmarket Surveillance Process

III. Postmarket Surveillance Plans

IV. When and How to Submit Postmarket Surveillance Reports

V. Content and Format of Postmarket Surveillance Reports

VI. Evaluation of Interim Postmarket Surveillance Reports

VII. Evaluation of Postmarket Surveillance Final Reports and Possible FDA Actions After 522 Order 

Completion

VIII. Manufacturer’s Reporting Status

IX. Postmarket Surveillance Status

X. Failure to Comply with Postmarket Surveillance Requirements under Section 522 of the FD&C 

Act

XI. Public Disclosure of Postmarket Surveillance Plan Information and Reports

Appendix 1: Section 522 Administrative Checklist Review

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GUIDANCE UPDATES

22
PAS/522 Guidance Updates

A. Timely submission and review of PAS protocols/522 plans and 

reports

B. Recommendations on study timeline/enrollment milestones

C. Submission of changes to an approved PAS protocol/522 plan

D. Study status categories

E. Transparency of posting interim/final results

F. Content of PAS protocols/522 plans and reports

– Minor updates to recommended elements

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A. Timely Submission and Review

of PAS Protocols/522 Plans

24

* per approval orders

‡ section 522(b)(1) of the FD&C Act and 21 CFR 822.8

§ per 21 CFR 822.17, FDA will review the 522 plan and respond within 60 days of receipt

• Sponsors and FDA should work collaboratively

– Early interactions (when possible)

• FDA intends to review PAS protocols/522 plans and issue a 

decision within 60 days of the approval/522 orders

Submission Type Sponsor Submission Timeline FDA Review Goal

PAS Protocol Submit with PMA or w/in 30 days* of order if 

PAS protocol not approved with PMA

Within 30 days of receipt

522 Plan Submit within 30 days of order‡ Within 30 days of receipt§
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Report 

Type*

Studies with New 

Enrollment

Studies without New 

Enrollment

Progress Semiannual until 100% 

enrolled†, annually thereafter

Semiannual in 1st year, 

annually thereafter

Enrollment As specified in the approval order or approved 522 plan

Final Three months from study completion (i.e., last subject’s 

last follow-up date)

Timely Submission and Review of Reports 

* FDA intends to review interim reports and final reports within 30 days and 60 days of receipt, respectively. 

† For the first 2 years and annually thereafter for 522 studies.

NOTE: Reporting schedule will be included in the PMA approval order or approved 522 plan

PAS Reporting from the date of the PMA approval order (or other agreed-upon starting date)

522 Reporting from the date of the 522 plan approval (or other agreed-upon starting date)
B. Study Timelines/ Enrollment 

Milestones

• Recommendations to ensure timely initiation and 

completion of PAS/522 studies

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Subject Enrollment PAS Timeline* 522 Timeline†

1st Subject 6 months 15 months‡

20% 12 months 18 months

50% 18 months 21 months

100% 24 months 24 months

* From study protocol approval date

† From date of issuance of the 522 order

‡ Per section 522(b)(1) of the FD&C Act
C. Changes to Approved 

PAS Protocol/522 Plan

• FDA generally does not intend for sponsors to routinely modify the 

PAS protocols/522 plans 

– FDA will consider changes on a case-by-case basis 

– Example of an appropriate change: When new information indicates that 

the original study enrollment milestones were impractical at the time of 

the PMA approval order/approval of 522 plan 

• FDA expects, only in limited circumstances, revisions to the original 

study milestones in the PMA approval order/approved 522 plan

• FDA will determine the study progress and designate study status 

based on the milestones specified in the PMA approval 

order/approved 522 plan 27
Reporting Study Delays and Mitigation Plans

• Reports should include:

– the causes for delays in study progress or failure to meet enrollment milestones; 

and 

– a plan to address challenges and meet established milestones.

• Mitigation efforts may include: 

– current and past enrollment recovery efforts;

– evaluation of slow enrollment; 

– device availability on the market; 

– measures taken to initiate study sites; 

– measures taken to incentivize study subjects; 

– outreach to study investigators and potential subjects; and 

– plans to remove barriers to site and subject participation. 

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D. Updated Study Status Categories

Previous Study Status 

Category Updated Study Status Category

Progress Adequate Ongoing: Study proceeding according to, or is ahead of, the study 

timelines in the approval order or the 522 plan.

Progress Inadequate Delayed: Study behind the study timelines in the approval order 

or 522 plan.

Revised/Replaced* Redesigned/Replaced: Study requirement cannot be fulfilled as 

originally designed and FDA has agreed to redesign or replace the 

PAS protocol/ 522 plan to fulfill the requirement.

Other Hold: Study has been placed on a hold temporarily, for example, 

because the device is no longer sold but the premarket submission 

associated with the requirement has not been withdrawn.

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*Revised/Replaced was previously only included in the 522 Guidance.
Updated Study Status Categories

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• New study status categories apply to new submissions received 

after publication of the final guidance documents (October 7, 

2022)

• For any submission received prior to October 7, 2022, the 

former study status categories will be used

• During a transition period, the Programs webpages will include 

both former and current study status categories until all study 

requirements receive a submission and FDA issues a decision on 

that submission
E. PAS Database

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www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma_pas.cfm
E. 522 Studies Database

32

www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pss.cfm
• FDA intends to post on its website, or otherwise make public, 

study interim results consistent with the Interim Data Release 

Plan

– Consistent with the Interim Data Release Plan; and/or

– When appropriate to protect public health

• Interim Data Release Plan in the PAS protocol/522 plan

– Frequency and type of interim analyses, data endpoints to be assessed 

and posted, and proposed frequency of posting on the FDA’s websites

• Sponsors can propose summary data in progress and final 

reports

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E. PAS/522 Transparency
Additional Resources

• Program Webpages

– Post-Approval Studies Program: www.fda.gov/medicaldevices/postmarket-requirements-devices/post-approval-studiesprogram

– 522 Postmarket Surveillance Studies Program: www.fda.gov/medicaldevices/postmarket-requirements-devices/522-postmarket-surveillancestudies-program

• Mandated Studies Programs Email

– MandatedStudiesPrograms@fda.hhs.gov

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Summary

• Postmarket mandated studies are important tools to ensure 

continued device safety and effectiveness

• Guidance document updates focused on activities to address 

postmarket questions in a timely manner

– Early and ongoing communication with manufacturers

– Collaborative establishment of protocol/plan, enrollment milestones, 

and study completion timelines to ensure that the studies achieve 

objectives and are completed in a timely manner 

– Timely reporting, review, and public posting of postmarket study 

information

35

Additional Panelists

Megan Gatski, PhD

General Health Scientist

Postmarket Programs Staff

Office of Product Evaluation and Quality 

Daniel Caños, PhD, MPH

Director

Office of Clinical Evidence and Analysis

Office of Product Evaluation and Quality

Minerva Hughes, JD, PhD

Regulatory Counsel

Office of Clinical Evidence and Analysis

Office of Product Evaluation and Quality

Hina M. Pinto

Acting Deputy Division Director

Division of Clinical Evidence and Analysis 1 

(Clinical Policy and Quality) 

Office of Clinical Evidence and Analysis

Office of Product Evaluation and Quality

Center for Devices and Radiological Health

U.S. Food and Drug Administration
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