Guidance for Industry and FDA Staff 

Real-Time Premarket Approval 

Application (PMA) Supplements 

Document issued on: April 28, 2006 

This document supersedes and replaces, the “Real-Time” Review Program for 

Premarket Approval Application (PMA) Supplements document last updated 

April 22, 1997 and Section II C, “PMA Supplements Definitions – Real Time 

Supplements” of the February 2003 guidance entitled, “Assessing User Fees: PMA 

Supplement Definitions, Modular PMA Fees, BLA and Efficacy Supplement 

Definitions, Bundling Multiple Devices in a Single Application, and Fees for 

Combination Products; Guidance for Industry and FDA” 

For questions regarding this document, contact Thinh Nguyen (CDRH) at 240-276-4010 or by e-mail 

at Thinh.Nguyen@fda.hhs.gov. For questions regarding the application of this guidance to devices 

regulated by the Center for Biologics Evaluation and Research (CBER), contact Leonard Wilson at 

301-827-0373 or by email at leonard.wilson@fda.hhs.gov. 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Devices and Radiological Health 

Center for Biologics Evaluation and Research 
Contains Nonbinding Recommendations 

Preface

Public Comment 

Written comments and suggestions may be submitted at any time for Agency 

consideration to the Division of Dockets Management, Food and Drug Administration, 

5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD, 20852. When submitting 

comments, please refer to the exact title of this guidance document. Comments may not 

be acted upon by the Agency until the document is next revised or updated. 

 

Additional Copies 

Additional copies are available from the Internet at: 

http://www.fda.gov/cdrh/ode/guidance/673.pdf, or by phone at (301) 827-2000 or (800) 

835-4709, or to receive this document by fax, call the CDRH Facts-On-Demand system 

at 800-899-0381 or 301-827-0111 from a touch-tone telephone. Press 1 to enter the 

system. At the second voice prompt, press 1 to order a document. Enter the document 

number (673) followed by the pound sign (#). Follow the remaining voice prompts to 

complete your request. 
Contains Nonbinding Recommendations 

Table of Contents 

I. Purpose...................................................................................................................... 1

II. Background .............................................................................................................. 1

III. Which modifications are appropriate for a Real-Time PMA Supplement? ...... 2

IV. How do I request a Real-Time review?.................................................................. 3

V. Is there a user fee for a Real-Time PMA Supplement?........................................ 4

VI. How do I submit a Real-Time PMA Supplement? ............................................... 5

VII. What should a Real-Time PMA Supplement contain? ........................................ 5

VIII.What is the format of a Real-Time review meeting?............................................ 6

Attachment I. Sample Real-Time Review Request....................................................... 7
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1

Guidance for Industry and FDA Staff 

Real-Time Premarket Approval 

Application (PMA) Supplements 

This guidance represents the Food and Drug Administration's (FDA's) current 

thinking on this topic. It does not create or confer any rights for or on any person and 

does not operate to bind FDA or the public. You can use an alternative approach if the 

approach satisfies the requirements of the applicable statutes and regulations. If you 

want to discuss an alternative approach, contact the FDA staff responsible for 

implementing this guidance. If you cannot identify the appropriate FDA staff, call the 

appropriate number listed on the title page of this guidance. 

I. Purpose 

This guidance provides information about the real-time review process for premarket 

approval application (PMA) supplements and outlines the procedures for requesting and 

submitting these types of documents. This guidance supersedes the document entitled 

"Real-Time" Review Program for Premarket Approval Application (PMA) Supplements, 

issued April 22, 1997 (the 1997 document) and Section II C, “PMA Supplements 

Definitions – Real Time Supplements” of the February 2003 guidance entitled, 

“Assessing User Fees: PMA Supplement Definitions, Modular PMA Fees, BLA and 

Efficacy Supplement Definitions, Bundling Multiple Devices in a Single Application, and 

Fees for Combination Products; Guidance for Industry and FDA.” 

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. 

II. Background 

On February 4, 2003, FDA published a Federal Register notice entitled, “Medical Device 

User Fee and Modernization Act of 2002, Establishment of a Public Docket”1 to provide 

an opportunity for interested persons to share information and views on the 

 

1

 68 FR 5643 
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implementation of the Medical Device User Fee and Modernization Act of 2002 

(MDUFMA).2

 Subsequently, FDA issued a guidance entitled “Assessing User Fees: 

PMA Supplement Definitions, Modular PMA Fees, BLA and Efficacy Supplement 

Definitions, Bundling Multiple Devices in a Single Application, and Fees for 

Combination Products”3

 and invited comments on its topics, which included Real-Time 

PMA Supplements. FDA received no comments on Real-Time PMA Supplements in 

either docket. 

In revising the 1997 document, FDA considered the comments submitted on it and other 

comments about Real-Time review presented at the MDUFMA Annual Stakeholder 

Meetings.4 Our revision incorporates the criteria for Real-Time PMA Supplements set 

forth in section 737(4)(D) of the Federal Food, Drug, and Cosmetic Act (the act) and 

clarifies the kinds of device modifications we believe are appropriate for real-time 

review. We continue to invite comments on this guidance. 

The Least Burdensome Approach 

We believe we should consider the least burdensome approach in all areas of medical 

device regulation. This guidance reflects our careful review of the relevant scientific and 

legal requirements and what we believe is the least burdensome way for you to comply 

with those requirements. However, if you believe that an alternative approach would be 

less burdensome, please contact us so we can consider your point of view. You may send 

your written comments to the contact person listed in the preface to this guidance or to 

the CDRH or CBER Ombudsman. Comprehensive information on CDRH's 

Ombudsman, including ways to contact him, can be found on the Internet at 

http://www.fda.gov/cdrh/resolvingdisputes/ombudsman.html and CBER’s Ombudsman 

can be reached at (301) 827-0379. 

III. Which modifications are appropriate for a RealTime PMA Supplement? 

According to section 737(4)(D) of the act,5 a Real-Time PMA Supplement is defined as: 

“a supplement to an approved premarket application or premarket report under 

section 515 that requests a minor change to the device, such as a minor change to the 

design of the device, software, sterilization, or labeling, and for which the applicant 

 

2

 Public Law 107-250 

3

 Issued on February 25, 2003, see www.fda.gov/cdrh/mdufma/guidance/1201.html. 4 Held December 3, 2003, November 18, 2004, and November 17, 2005. 

5 As amended by the Medical Devices Technical Corrections Act (Public Law 108-214).
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[PMA holder] has requested and the agency has granted a meeting or similar forum to 

jointly review and determine the status of the supplement.” 

In general, we believe a Real-Time PMA Supplement is appropriate for a minor change 

that can be expected within a product line, which includes changes to: 

• device design

• software

• instructions for use, warnings, or precautions or other labeling that does not affect 

the indications or contraindications 

• sterilization and packaging methods.

In addition, a minor change should be one that is: 

• expected for that device type 

• validated according to scientific principles we have relied on in previous reviews 

and accepted test methods or procedures for devices of that type, wherever 

applicable, such as an FDA-recognized standard or guidance document 

• adequately supported by pre-clinical or animal testing, with no new clinical data 

• typically involving review within a single scientific discipline, rather than a 

multidisciplinary review.6 

We also believe that for a Real-Time PMA Supplement to be an effective route to market, 

FDA and the PMA holder should agree that the review can be achieved in a “real-time” 

setting before either initiates the process. 

IV. How do I request a Real-Time review? 

The typical request for a Real-Time review will follow these 4 steps. 

1. Preliminary Discussion 

Before submitting your request, we recommend you contact the branch chief in the 

appropriate review division in CDRH or the applications division in the appropriate 

 

6

 A review from a single scientific discipline may be, for example, an electrical 

engineering, mechanical engineering, chemical engineering, material engineering, 

microbiology, or biocompatibility review. 
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CBER office to discuss whether the modification to your device is appropriate for a 

Real-Time PMA Supplement.7

 

2. Your Request 

After you and FDA agree that the review can be achieved in a “real-time” setting, we 

recommend you fax your request for a Real-Time review to the appropriate CDRH 

branch chief or CBER applications division and follow with a hard copy to the 

Document Mail Center of the appropriate Center. We recommend that your request 

include the information outlined in the Sample Real Time Review Request in 

Attachment I. 

3. FDA’s Response 

FDA plans to respond by fax within 14 days of receipt of Real-Time review requests 

to the Document Mail Center. Generally, if the information in your request is 

consistent with your preliminary discussion with FDA, and FDA, after evaluating the 

information, believes the modification is “minor” as defined in section III, FDA will 

grant your request. 

4. Type of Interaction 

We intend the review process for a Real-Time PMA Supplement to be interactive, 

although a face-to-face meeting may not always be part of the process. We will work 

with you to determine the type of interaction appropriate based on the information in 

your request. If you and FDA agree a meeting is appropriate, FDA’s response will 

also confirm a meeting date, which should be within 30 days of the proposed 

submission date of the supplement or the earliest date that both you and FDA 

personnel are available to meet. 

V. Is there a user fee for a Real-Time PMA 

Supplement? 

Yes. As with all fee-paying submissions, the fee for a Real-Time PMA Supplement is 

due upon submission of the supplement. If FDA receives the supplement prior to 

payment, we will place the file on hold until we receive payment and notify you by 

 

7

 For assistance in identifying the appropriate review branch in CDRH, the applicant may 

contact the Division of Small Manufacturers, International, and Consumer Assistance 

(DSMICA). Please see http://www.fda.gov/cdrh/devadvice/36f.html for contact options. 

For assistance in identifying the appropriate division in CBER, please contact the Office of 

Communication, Training and Manufacturers Assistance at 1-800-835-4709 or please see 

http://www.fda.gov/cber/inside/orgover.pdf. 
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facsimile.8

 FDA begins its review when the Office of Financial Management notifies 

CDRH or CBER that payment has been received and we have received the PMA 

submission. See http://www.fda.gov/oc/mdufma for information on remitting user fees. 

VI. How do I submit a Real-Time PMA Supplement? 

We recommend you submit at least 3 copies of your Real-Time PMA Supplement to the 

appropriate Center at the address below. 

Each copy should be labeled “REAL-TIME REVIEW REQUEST GRANTED” and 

contain a copy of FDA’s response granting your request for a Real-Time review. 

If we have scheduled a meeting with you, we recommend you submit your Real-Time 

PMA Supplement sufficiently in advance to allow FDA reviewers to adequately prepare 

their reviews. If we have not received your submission at least 3 weeks before the 

meeting, we will typically reschedule to assure reviewers have adequate preparation time 

in order to avoid an unproductive meeting. 

CDRH Review 

PMA Document Mail Center (HFZ-401) 

Office of Device Evaluation 

Center for Devices and Radiological Health 

9200 Corporate Boulevard 

Rockville, MD 20850 

CBER Review 

Food and Drug Administration 

Center for Biologics Evaluation and Research 

Document Control Center, HFM-99, Suite 200N 

Rockville, MD 20852-1448 

VII. What should a Real-Time PMA Supplement 

contain? 

A Real-Time PMA Supplement should identify all modifications planned for the device 

and labeling. We recommend you include testing and results, along with a detailed risk 

 

8

 Section 102 of MDUFMA authorizes FDA to put the submission on hold until payment 

is received. 
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analysis to support the continued safety and effectiveness of the modified device. Your 

risk analysis should include a thorough assessment of all potential hazards associated 

with device use, taking into account the (incremental) modification proposed in your 

submission and the (cumulative) effects of any preceding modifications made since the 

approval of the original PMA. Your risk analysis should also identify the steps you have 

taken to minimize any additional risks that may be created by incremental or cumulative 

modifications. 

VIII. What is the format of a Real-Time review 

meeting? 

If a Real-Time review meeting is part of the process, the meeting generally proceeds as 

follows: 

1. You present the changes to your device, results of testing to support those 

changes, and your risk analysis. 

2. You and FDA discuss any questions or comments about the changes, testing, or 

risk analysis. 

3. The meeting briefly adjourns to allow for discussion amongst FDA staff. 

4. FDA generally gives you verbal feedback that day. 

After the meeting, FDA will typically send our decision letter (i.e., approval, approvable, 

or not approvable letter) by fax, with a hard copy to follow. 
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Attachment I. Sample Real-Time Review Request 

PMA Contact Information and Submission Information Date: 

Name: 

Address 

Company: 

Phone Number: 

Fax Number: 

PMA Document Number: 

Target Date for submitting to FDA: 

Proposed Meeting Date(s): 

Reason(s) for submission (check one or more) 

 Minor design changes 

 Material changes to another known material 

 Minor labeling changes 

 Software change 

 Sterilization changes to another known method 

 Packaging changes 

 Other 

We recommend that you attach a one-page or less explanation for the requested 

change(s) including: 

 the test methods identified in FDA guidance or recognized standard, if applicable 

 identify under what submission we have previously reviewed these test methods, if 

applicable 

 a summary of your risk analysis 

Specify the type of meeting you are requesting (check one or more) 

 Face-to-face 

 Telephone conference 

 Video conference 

 Other (Explain)