Premarket Approval Application 

(PMA) Program:

Postapproval Requirements

Diane Nell, Ph.D.

Premarket Programs Branch

Division of Industry and Consumer Education

Office of Communication and Education

Center for Devices and Radiological Health

U.S. Food and Drug Administration

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Approved PMA

Postapproval

Requirements

2
• Define PMA

• Understand regulatory controls

• Understand regulatory responsibilities for an approved PMA:

– Post-approval studies (PAS) and reports

– Amendments

– Supplements

– 30-Day Notices

– Postapproval periodic reporting (annual reports)

Learning Objectives

3
• Marketing application for a Class III medical device 

(21 CFR 814.3(e))

• Class III, highest risk devices

• Support or sustain human life, substantial importance in 

preventing impairment of human health, potential for 

unreasonable risk of illness or injury

• Unable to solely rely on general and special controls to 

reasonably assure safety and effectiveness

PMA

(21 CFR 814)

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What are “Regulatory Controls”

• Apply to a particular device type

• Describe appropriate level of regulatory burden or oversight 

to ensure safety and effectiveness

• Generally broad, but may be specific

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• Increased risk of device  increased regulatory controls

• Regulatory Controls webpage

Regulatory Controls

Class Risk Controls

I low general

II moderate general and special

III high general and PMA

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Postapproval Controls for 

Approved PMA Devices

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PMA Postapproval Controls

• Postapproval studies (PAS) and reports

• Amendments

• Supplements

• 30-Day Notices

• Postapproval periodic reporting (annual reports)

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Post-Approval Studies (PAS)

• May be required at time of approval, as a condition of approval 

• FDA and Applicant agree on general purpose and outline

• Distinct from postmarket surveillance/522 studies, which may be 

required any time after PMA approval

• Resources:

• Regulation: 21 CFR 814.82

• Webpage: Post-Approval Studies and the PAS FAQs

• Guidance: “Procedures for Handling Post-Approval Studies Imposed by PMA Order”

• Database: Post-Approval Studies (PAS) 9
Post-Approval Study Reports

• Study information:

– Purpose, goals, objectives and endpoints, and patient population being 

studied

• Summary of study progress:

– IRB approvals

– Number of clinical sites

– Enrollment status

• Summary of safety and/or effectiveness data and an 

interpretation of study results 10
Amendments

• Time-sensitive updates that do not affect safety and 

effectiveness

• Examples:

– Change in ownership

– Change in contact information (e.g., company name, official correspondent, 

address)

– Voluntary market withdrawal (cease marketing)

• Resources:

• Regulation: 21 CFR 814.37

• Webpage: PMA Supplements and Amendments 11
Supplements

• Changes affecting safety or effectiveness

• Required prior to implementing the change(s)

• Examples:

– New indication for use

– Changes in design, packaging, or labeling

– Changes in manufacturing site

• Resources:

• Regulation: 21 CFR 814.39

• Webpage: PMA Supplements and Amendments 12
Supplements

• Types of PMA Supplements

– Panel-Track supplement

– 180-Day supplement

– Real-Time supplement

– Special PMA supplement - Changes Being Effected

– Manufacturing site change supplement

• Resources:

• Guidance: “Modifications to Devices Subject to Premarket Approval (PMA) - The PMA 

Supplement Decision-Making Process” 13
Supplements – Panel Track

• Significant change requiring new substantial clinical data

• Examples:

– New indication for use

– Design

– Performance

– Change or removal of contraindication

• Resources:

• Act: 21 U.S.C. 379i(4)(B) 14
Supplements – Panel Track

• Case Example:

– Prosthetic heart valve

– New indication for use: aortic valve to be used in mitral position

– No change in design

– New environment can impact performance  new clinical data needed

– Appropriate for Panel Track supplement

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Supplements – 180-Day

• Significant change requiring new preclinical test data

• Original clinical data are still applicable

• May include limited, confirmatory clinical data

• Examples:

– Design, Software, Labeling, Trade name change

• Resources:

• Act: 21 U.S.C. 379i(4)(C)

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Supplements – 180-Day

• Case Example:

– Ventricular assist device (VAD)

– New design for the lead

– No change to indication for use or patient population

– Mechanical testing, only

– No new clinical data needed

– 180-Day supplement appropriate

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Supplements – Real-Time

• Minor changes supported by pre-clinical or animal testing, with no 

new clinical data

• Involve review within a single scientific discipline, rather than 

multidisciplinary review

• Meeting, or similar forum, to jointly review and determine status of 

supplement

• Prior to submitting, must obtain concurrence from FDA review team

• Refer to “Real-Time” guidance (see next slide) for procedure to submit 

Real-Time supplement; email may be used instead of fax

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• Examples:

– Design

– Software

– Labeling

– Sterilization and packaging methods

• Resources:

• Act: 21 U.S.C. 379i(4)(D)

• Guidance: “Real-Time Premarket Approval Application (PMA) Supplements”

Supplements – Real-Time

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• Case Example:

– Alternate sterilization method

– Previously reviewed and approved for this device type

– Validation testing, only

– Single discipline of sterilization

– Real-Time supplement appropriate

Supplements – Real-Time

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• Must enhance safety

• May include labeling and/or manufacturing changes

• No design changes

• Narrow exception to the general rule of prior FDA approval

of changes to a PMA

Supplements – Special

Changes Being Effected

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• Examples:

– Improved labeling (e.g., add/strengthen a contraindication, warning, 

precaution)

– Additional manufacturing quality assurance step; may not impact 

effectiveness

• Resources:

• 21 CFR 814.39(d)(1) and (d)(2)

Supplements – Special

Changes Being Effected

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• Case Example:

– Improved labeling instructions

– No impact on effectiveness

– Special – Changes Being Effective supplement appropriate

Supplements – Special

Changes Being Effected

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Supplements –

Manufacturing Site Change

• Use of a different site or moving the manufacturing site 

180-day “site change supplement”

• Supplement must demonstrate compliance with QS regulation 

(21 CFR 820)

• Preapproval inspection may be necessary

• Resources:

• Guidance: “Manufacturing Site Change Supplements: Content and Submission”

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Supplements

Supplement Clinical Data Preclinical 

Data

Single Review 

Discipline/Area

FDA Review

Panel-Track ✓ x ✓ 320

180-Day x ✓ x 180

Real-Time x ✓ ✓ 90

Special x x x Change may be 

implemented 

prior to FDA 

approval order

Mfg Site 

Change

x x ✓ 180

✓applicable

x not applicable 25
30-Day Notice

• Written notification of change in manufacturing procedure or 

method, affecting safety and effectiveness

• May distribute 30 days after notification, unless:

– FDA notifies applicant of conversion to 135-Day supplement

– FDA describes further information/action required

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30-Day Notice

• Examples:

– Manual to automated process

– Alternate supplier

– Modified sterilization process parameters

• Resources:

• Guidance: “30-Day Notices, 135-Day Premarket Approval (PMA) Supplements and 75-

Day Humanitarian Device Exemption (HDE) Supplements for Manufacturing Method or 

Process Changes”

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Postapproval Periodic Reports

• Also known as PMA “annual report”

• Due annually from date of approval

(e.g., if PMA is approved Feb. 1, 2019, then report is due by Feb. 1, 2020, 2021, etc.)

• Requirement will cease only upon PMA withdrawal

• MDUFA* fee; invoice is mailed to applicant

(no Form FDA 3601 is needed)

* MDUFA = Medical Device User Fee Amendments

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Postapproval Periodic Reports

• Includes:

– Changes submitted as supplements, plus other changes, not previously submitted

– Summary and bibliography of published and unpublished reports

– Number devices shipped or sold; number implanted (as applicable)

• Resources:

• Regulation: 21 CFR 814.82(a)(7) and 21 CFR 814.84

• Webpage: Postapproval (Annual) Reports section of PMA Postapproval Requirements

• Guidance: “Annual Reports for Approved Premarket Approval Applications (PMA)”

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Summary

• Class III medical device are subject to PMA controls after approval

• PMA controls feature these types of postapproval submissions:

– Post-approval studies (PAS) and reports

– Amendments

– Supplements

– 30-Day Notices

– Postapproval periodic reporting (annual reports)

• Each submission type addresses different aspects of postapproval

activity related to the device

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Resources

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Slide 

Number

Cited Resource URL

4 21 CFR 814 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=814

4 21 CFR 814.3(e) https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=814.3

6 Regulatory Controls (webpage) https://www.fda.gov/medical-devices/overview-device-regulation/regulatory-controls

9 21 CFR 814.82 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=814.82

9 Post-Approval Studies (webpage) https://www.fda.gov/medical-devices/postmarket-requirements-devices/post-approval-studies

9 PAS FAQs (webpage) https://www.fda.gov/medical-devices/post-approval-studies/post-approval-studies-pasfrequently-asked-questions-faq

9 “Procedures for Handling Post-Approval 

Studies Imposed by PMA Order” (guidance)

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/procedureshandling-post-approval-studies-imposed-pma-order

9 Post-Approval Studies (database) https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma_pas.cfm

11 21 CFR 814.37 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=814.37

11, 12 PMA Supplements and Amendments 

(webpage)

https://www.fda.gov/medical-devices/premarket-approval-pma/pma-supplements-andamendments
Resources (continued)

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Slide 

Number

Cited Resource URL

12 21 CFR 814.39 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=814.39

13 “Modifications to Devices Subject to 

Premarket Approval (PMA) - The PMA 

Supplement Decision-Making Process” 

(guidance)

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/modificationsdevices-subject-premarket-approval-pma-pma-supplement-decision-making-process

14 21 U.S.C. 379i(4)(B) https://uscode.house.gov/view.xhtml?req=(title:21%20section:379i%20edition:prelim)%20OR%20

(granuleid:USC-prelim-title21-section379i)&f=treesort&edition=prelim&num=0&jumpTo=true

16 21 U.S.C. 379i(4)(C) https://uscode.house.gov/view.xhtml?req=(title:21%20section:379i%20edition:prelim)%20OR%20

(granuleid:USC-prelim-title21-section379i)&f=treesort&edition=prelim&num=0&jumpTo=true

19 21 U.S.C. 379i(4)(D) https://uscode.house.gov/view.xhtml?req=(title:21%20section:379i%20edition:prelim)%20OR%20

(granuleid:USC-prelim-title21-section379i)&f=treesort&edition=prelim&num=0&jumpTo=true

19 “Real-Time Premarket Approval Application 

(PMA) Supplements” (guidance)

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/real-timepremarket-approval-application-pma-supplements

22 21 CFR 814.39(d)(1) and (d)(2) https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=814.39

24 21 CFR 820 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=820
Resources (continued)

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Slide 

Number

Cited Resource URL

24 “Manufacturing Site Change Supplements: 

Content and Submission” (guidance)

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/manufacturingsite-change-supplements-content-andsubmission?utm_campaign=Final%20Guidance%20on%20Manufacturing%20Site%20Change%20S

upplements

27 “30-Day Notices, 135-Day Premarket 

Approval (PMA) Supplements and 75-Day 

Humanitarian Device Exemption (HDE) 

Supplements for Manufacturing Method or 

Process Changes” (guidance)

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/30-day-notices135-day-premarket-approval-pma-supplements-and-75-day-humanitarian-device-exemption

29 21 CFR 814.82(a)(7) https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=814.82

29 21 CFR 814.84 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=814.84

29 Postapproval (Annual) Reports (section of 

PMA Postapproval Requirements webpage)

https://www.fda.gov/medical-devices/premarket-approval-pma/pma-postapprovalrequirements#postapproval

29 PMA Postapproval Requirements (webpage) https://www.fda.gov/medical-devices/premarket-approval-pma/pma-postapproval-requirements

29 “Annual Reports for Approved Premarket 

Approval Applications (PMA)” (guidance)

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/annual-reportsapproved-premarket-approval-applications-pma
Your Call to Action

• Review all relevant cited references:

– Regulations (Code of Federal Regulations)

– FDA guidance documents

– Device Advice webpages

– CDRH Learn

• Contact the Division of Industry and Consumer Education

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DICE Contact

• Phone: (800) 638-2041 

• Monday – Friday:

• 9:00 am – 12:30 pm; 1:00 pm - 4:30 pm

• Email: dice@fda.hhs.gov

• respond within 2 business days

www.fda.gov/DICE

www.fda.gov/DeviceAdvice

www.fda.gov/CDRHLearn

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