Introduction to the Premarket 

Approval Application (PMA) 

Program 

Donna Headlee, RN, BSN, CCRP

Branch Chief, 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
PMA Devices

1 2

3 4

2
Learning Objectives

1. Define PMA 

2. Describe the contents of a PMA application

3. Describe FDA review process of a PMA

4. Discuss key milestone interactions and actions

5. Identify strategies for a successful PMA application 

and review process

3
Class III Medical Devices

• Highest risk category

• Subject to PMA requirements

• 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 assure safety 

and effectiveness

4
Content of PMA

5
Contents of PMA

• Name and address of applicant

• Table of contents

• Indications for use

• Description of device and functional components or ingredients

• Reference to performance standards

• Environmental assessment

21 CFR 814.20

www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=814.20

6
Contents of PMA

• Manufacturing

• Bibliography

• Sample of device, if practical

• Proposed labeling

• Financial certification or disclosure

• Information concerning uses in pediatric patients

21 CFR 814.20

www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=814.20

7
Contents of PMA

Pre-Clinical Studies

• Test reports, summaries and conclusions

• Example Categories include: 

– Bench and animal testing

– Biocompatibility

– Software

– Engineering

– Electromagnetic Compatibility (EMC)

– Electromagnetic Interference (EMI)

21 CFR 814.20

www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=814.20

8
Contents of PMA

Clinical Studies

• Any clinical experience, within and outside United States

• Support safety and effectiveness

• Support benefit-risk determination

• Include all data, whether adverse or supportive:

– methods 

– results

– conclusions 

 Reasonably obtainable by applicant

9

21 CFR 814.20

www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=814.20
PMA Review Process

10
• Team Leader/Lead 

Reviewer

• Clinical

• Statistical

• Preclinical

• Engineering

• Animal Studies

• Biocompatibility

• Microbiology

• Quality System and 

Manufacturing

• Bioresearch Monitoring

• Patient Labeling

• Epidemiology

Scientific, Regulatory, Quality System Review

Multi-Disciplinary FDA Review Team

11
PMA Review Process (1/2)

Acceptance 

Review

Filing 

Review

Substantive 

Review

Day 

15

Not Accepted Accepted

Day 

45

Not Filed Filed

Submit PMA Application

12
PMA Review Process (2/2)

Substantive 

Interaction (SI)

Medical Device 

User Fee 

Amendments 

(MDUFA) 

Decision

Proceed Interactively (PI) Major Deficiency Letter

Approval Not Approvable

Day 

90

Day 

180/320

Day 100 Meeting 

(Requested by 

Applicant)

Advisory Panel Meeting

(if applicable)

Approvable Pending Deficiencies

Approvable Pending GMPs

or

)13
• Purpose

– Assess administrative completeness of application

– Does Application contain required elements per 21 CFR 814.20?

• FDA Action:

– FDA sends Applicant email notification

– Decision Options: Accepted or Not Accepted (identify missing elements)

– Completed within 15 calendar days of FDA’s receipt of PMA

Acceptance Review

Acceptance and Filing Reviews for PMAs

www.fda.gov/regulatory-information/search-fda-guidance-documents/acceptanceand-filing-reviews-premarket-approval-applications-pmas

14
• Purpose

– Threshold determination that application is sufficiently complete to 

review

• Adequacy of technical elements allow for substantive review 

– Evaluate whether data are consistent with protocol, final device design, 

and proposed indications

• FDA Action:

– FDA sends Applicant notification of filing review

– Decision Options: Filed or Not Filed

– Completed within 45 calendar days of FDA receipt of PMA

Filing Review

15
Substantive Review

• Purpose

– In-depth Scientific, Regulatory, and Quality System Reviews

• Interactive Process

– Interact with applicant to address deficiencies

• that can be addressed in appropriate timeframe

16
Substantive Interaction (SI)

• Purpose:

– FDA to provide a major interaction including feedback/action by Day 90 

• FDA Options:

1. Continue to work interactively with applicant

– Proceed interactively

– Application remains under review (i.e., not placed on hold)

2. Issue Major Deficiency Letter

– Application is placed on hold until complete response is made to deficiencies

17
Advisory Committee Review

• Independent panel of experts

– Clinical practice, academia, statistics, industry, patients 

and any additional expertise needed

• Open to the public

Procedures for Meetings of the Medical Devices Advisory Panel Committee

www.fda.gov/regulatory-information/search-fda-guidance-documents/proceduresmeetings-medical-devices-advisory-committee

18
FDA MDUFA Decisions

19
FDA Review Decisions

• Approval Order:

– Device may be marketed

– Identifies conditions of approval

20
FDA Review Decisions

• Approvable Pending Deficiencies Letter:

– Device can not be marketed

– Identify clarifications/deficiencies to be addressed before 

PMA may be approved

– Common issues:

• unresolved labeling

• unresolved post-approval study design

21
FDA Review Decisions

• Approvable Pending GMP Letter:

– Device can not be marketed

– Primary reason: FDA has not confirmed that 

manufacturing facilities, methods and controls are in 

compliance with Quality System

22

Quality System - 21 CFR Part 820

www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=820
FDA Review Decisions

• Not Approvable Letter:

– Device can not be marketed

– Identify deficiencies that need to be addressed to make the 

PMA application approvable

– May include requests for new clinical and/or preclinical data

23
Summary of Safety and

Effectiveness Data (SSED)

• FDA summarizes basis for PMA Approval

• Provides comprehensive, detailed summary and analysis of PMA:

– Device and Background Information: device description, indications for 

use

– Performance Testing: preclinical, animal, and clinical

– Review of Panel meeting

– Benefit/Risk summary

24

PMA Approval Database

www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm
Strategies for a Successful

PMA Application

25
• Be organized

• Be prepared

• Be responsive 

Successful Strategies

3 B’s

26
Be Organized

• Well-organized application

• Administratively and scientifically 

complete application 

27
Be Prepared

• Have your team ready to answer questions

• Have copies of PMA and make available any 

previously submitted information (e.g., IDE, Qsubmission)

• Be ready for manufacturing (Quality System) and 

bioresearch monitoring (BIMO) inspections

28
Be Responsive 

• Be upfront and responsive

– Answer FDA’s questions when you say you will

– If you don’t understand a question, call/email and ask for clarification

– Plan a Day 100 meeting - you can always cancel if it is not needed 

• Start early to develop your post-approval study plan

– Work with FDA study team to gain agreement on post approval study

29
References 

• Factors to Consider When Making Benefit-Risk Determinations in Medical Device 

Premarket Approval and De Novo Classifications

www.fda.gov/regulatory-information/search-fda-guidance-documents/factors-consider-whenmaking-benefit-risk-determinations-medical-device-premarket-approval-and-de

• Balancing Premarket and Postmarket Data Collection for Devices Subject to 

Premarket Approval

www.fda.gov/regulatory-information/search-fda-guidance-documents/balancing-premarketand-postmarket-data-collection-devices-subject-premarket-approval

30
References 

• Acceptance of Clinical Data to Support Medical Device Applications and 

Submissions Frequently Asked Questions

www.fda.gov/regulatory-information/search-fda-guidance-documents/acceptanceclinical-data-support-medical-device-applications-and-submissions-frequently-asked

• Use of Real-World Evidence to Support Regulatory Decision-Making for Medical 

Devices

www.fda.gov/regulatory-information/search-fda-guidance-documents/use-realworld-evidence-support-regulatory-decision-making-medical-devices

31
References 

• The Least Burdensome Provisions: Concept and Principles

www.fda.gov/regulatory-information/search-fda-guidance-documents/least-burdensomeprovisions-concept-and-principles

• Guidance on PMA Interactive Procedures for Day 100-Meetings and Subsequent Deficiencies

www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-pmainteractive-procedures-day-100-meetings-and-subsequent-deficiencies-use-cdrh-and

• FDA and Industry Actions on Premarket Approval Applications (PMAs): Effect on FDA 

Review Clock and Goals

www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industryactions-premarket-approval-applications-pmas-effect-fda-review-clock-and-goals

32
• A PMA is a marketing application for the highest risk of medical 

devices that FDA regulates

• A PMA application includes valid scientific evidence to support 

the reasonable assurance of safety and effectiveness of the 

device for the intended use

• The PMA review process is a multidisciplinary, collaborative, 

and interactive process

Summary

33
Providing Industry Education

1. CDRH Learn – Multi-Media Industry Education

• Videos, audio recordings, power point presentations, software-based 

“how to” modules describing aspects of medical device and radiation 

emitting product regulations:

www.fda.gov/CDRHLearn

2. Device Advice – Text-Based Education

• Text-based resource that explains many aspects of medical device 

laws, regulations, guidances, and policies: 

www.fda.gov/DeviceAdvice

3. Division of Industry and Consumer Education (DICE)

• If you have a question - Email: DICE@fda.hhs.gov

• Phone: 1(800) 638-2041 or (301) 796-7100 (Live Agents 9am – 12:30 

pm; 1-4:30 pm EST) 34
Your Call to Action

• Work with the Agency before and during the PMA 

review process

• Submit a well-organized PMA

• Provide valid scientific evidence to support the 

reasonable safety and effectiveness of the medical 

device for the intended use

35
36