**Guidance for Industry and FDA Staff**

Premarket Approval Application Modular Review

**Document issued on: \[Level 1 Immediately in Effect, NOA sign off
date\]**

**This document supersedes and replaces, "A Modular Approach to PMA
Review," dated January 29, 1998, and "Guidance for the Medical Device
Industry on PMA Shell Development and Modular Review," dated November 6,
1998.**

For questions regarding this document, contact Nicole Wolanski (CDRH) at
301-594-2186 or by e-mail at nlw@cdrh.fda.gov. For questions regarding
the application of this guidance to devices regulated by the Center for
Biologics Evaluation and Research (CBER), contact Robert Yetter at (301)
827-0373 or by e-mail at Yetter@cber.fda.gov.

![](media/image1.png){width="0.9631944444444445in"
height="1.0763888888888888in"}

**U.S. Department of Health and Human Services**

**Food and Drug Administration**

**Center for Devices and Radiological Health**

![](media/image2.png){width="1.0625in"
height="0.9479166666666666in"}**Center for Biologics Evaluation and
Research**

**Preface**

**Public Comment**

Written comments and suggestions may be submitted at any time for Agency
consideration to Dockets Management Branch, Division of Management
Systems and Policy, Office of Human Resources and Management Services,
Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305),
Rockville, MD, 20852. Alternatively, electronic comments may be
submitted to <http://www.fda.gov/dockets/ecomments>. Please identify
your comments with the docket number listed in the notice of
availability that publishes in the *Federal Register* announcing the
availability 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/%5Bspecific> address\] or
<http://www.fda.gov/cber/mdufma/mdufma.htm>, 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 (**835**)
followed by the pound sign (#). Follow the remaining voice prompts to
complete your request.

**Table of Contents**

[**I.** **Purpose** 1](#i.-purpose)

[**II.** **Background** 1](#ii.-background)

[**The Least Burdensome Approach** 3](#the-least-burdensome-approach)

[**III.** **Consultation with Stakeholders**
3](#iii.-consultation-with-stakeholders)

[**IV.** **Scope** 4](#iv.-scope)

[**V.** **Definitions** 4](#v.-definitions)

[**VI.** **User Fee Considerations for Modular Review**
4](#vi.-user-fee-considerations-for-modular-review)

[**VII.** **Industry Instructions for Submitting a Modular PMA**
5](#vii.-industry-instructions-for-submitting-a-modular-pma)

[Contact Review Group 5](#contact-review-group)

[**A.** **PMA Shell** 5](#a.-pma-shell)

[1. Determination that PMA Review is Appropriate for the Device
5](#determination-that-pma-review-is-appropriate-for-the-device)

[2. Content of a PMA Shell 6](#content-of-a-pma-shell)

[3. Informal Review of the Proposed PMA Shell
7](#informal-review-of-the-proposed-pma-shell)

[4. Submission of the PMA Shell 7](#submission-of-the-pma-shell)

[5. Changes to the Accepted PMA Shell
7](#changes-to-the-accepted-pma-shell)

[**B.** **PMA Modules** 8](#b.-pma-modules)

[1. Submission of Each PMA Module 8](#submission-of-each-pma-module)

[2. Incomplete PMA Modules 8](#incomplete-pma-modules)

[3. Time Frame for Reviewing a PMA Module
8](#time-frame-for-reviewing-a-pma-module)

[4. Reopening a Closed PMA Module 9](#reopening-a-closed-pma-module)

[5. Submission of the Final PMA Module
9](#submission-of-the-final-pma-module)

[6. Filing of the Modular PMA 9](#filing-of-the-modular-pma)

[**Attachment I Modular PMA Flow** 11](#attachment-i-modular-pma-flow)

[**Attachment II Sample PMA Shell** 12](#attachment-ii-sample-pma-shell)

[**Attachment III Frequently Asked Questions**
13](#attachment-iii-frequently-asked-questions)

**Guidance for Industry and FDA Staff**

**Premarket Approval Application Modular Review**

***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**

The purpose of this guidance document is to provide industry and FDA
staff with information regarding the premarket approval application
(PMA) modular review program and to outline the procedures for
submitting or reviewing a modular PMA.

This guidance supersedes and replaces the documents entitled, "A Modular
Approach to PMA Review," dated January 29, 1998, and "Guidance for the
Medical Device Industry on PMA Shell Development and Modular Review,"
issued on November 6, 1998 (hereinafter referred to as the 1998
Guidances).

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**

In a traditional PMA, the applicant submits all PMA data, as outlined in
21 CFR 814.20, at the same time, regardless of when testing is
completed. FDA begins its review only upon receipt of all the required
information. In 1998, however, as part of CDRH's reengnineering effort,
FDA issued the above mentioned guidances. In these documents, FDA
described a new policy whereby applicants could submit "Modular PMAs."
The goal of FDA's 1998 Guidances was to increase the efficiency of the
PMA review process by allowing applicants to submit discrete sections
(modules) of the PMA to FDA for review soon after completing the testing
and analysis.

FDA intends the modular review approach to provide a mechanism by which
applicants may submit preclinical data and manufacturing information for
review while still collecting, compiling, and analyzing the clinical
data. Therefore, a modular PMA is a compilation of sections or
\"modules\" submitted at different times that together become a complete
application. Additionally, the modular approach allows the applicant to
potentially resolve any deficiencies noted by FDA earlier in the review
process than would occur with a traditional PMA application.

On October 26, 2003, the Medical Device User Fee and Modernization Act
of 2002 (MDUMFA), Public Law 107-250 was enacted. Section 209 of MDUFMA
amended the Federal Food, Drug and Cosmetic Act (the act) to codify the
modular review approach.[^1] In recognition that the agency would need
to issue updated guidance to reflect the new statutory provision, FDA
requested comments on its modular PMA review program. 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
(68 FR 5643)(hereinafter referred to as the MDUFMA Docket). In addition,
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."[^2] In the guidance, FDA asked for comments on
the various topics discussed in the document, including modular review
of PMAs.

Since 1998, FDA has gained considerable experience with modular PMA
submissions. Based on FDA's experience prior to the enactment of MDUFMA
and comments submitted to the MDUFMA Docket, FDA is issuing this
guidance to replace the 1998 Guidances. These changes include:

-   clarifying that modular review should be limited to original PMAs
    (i.e., modular review is not ordinarily appropriate for PMA
    supplements)

-   modifying the procedures for preparing and submitting a modular PMA

-   explaining the significance of timing for submission of the modules

-   revising the sample shell and specifying the expected content of the
    modules

-   suggesting limitations to the total number of modules that should be
    submitted.

The agency expects these changes to: 1) help clarify which PMAs are
appropriate for modular review, 2) simplify submission procedures, and
3) improve the efficiency of FDA's review. Additionally, we have added
guidance addressing user fee payment procedures for modular PMAs.

# **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]{.underline}](http://www.fda.gov/cdrh/resolvingdisputes/ombudsman.html)
and CBER's Ombudsman can be reached at (301) 827-0379.

# **III. Consultation with Stakeholders**

In developing this guidance, FDA has considered comments on the PMA
modular review program that were submitted to the MDUFMA Docket. As
mentioned above, FDA also issued the Assessing User Fees guidance and
asked for comments on modular review in that document.[^3]

To date, FDA has received comments on modular PMA review submitted to
the MDUFMA docket from one stakeholder. One comment requested that FDA
expand the scope of modular review, now limited to original PMAs, to
certain PMA supplements. In the agency's experience, reviews of
applications that are supplements to an already approved device do not
ordinarily lend themselves to a modular format because the changes do
not usually involve multiple modules. In addition, the agency currently
does not have the resources that would be required to expand the
program. Therefore, this guidance addresses procedures solely for the
modular review of original PMAs.

Another comment requested that FDA respond to incomplete modules in an
abbreviated timeframe (i.e., 75 days rather than the 90 review that
traditionally has been used by the agency). At this time, FDA believes
that the current review timeframe represents a realistic projection of
what the Food and Drug Administration\'s Center for Devices and
Radiological Health and Center for Biologics Evaluation and Research can
accomplish. However, as stated in the letter from the Secretary of
Health and Human Services to Congress that accompanies the user fee
legislation,[^4] FDA agreed to work with its stakeholders to develop
appropriate performance goals for this program once it is fully
implemented. FDA will also re-examine the modular review timeframe at
that time.

One comment requested that FDA assess user fees on modular PMAs only if
the initial module was submitted on or after October 1, 2002. FDA agrees
with this comment and will not assess user fees retroactively for
modular PMAs first submitted before October 1, 2002.

Finally, one comment requested FDA to develop a question and answer
styled text explaining PMA modular review. We have done so and included
it as an attachment to this guidance document.

We continue to invite comments on this guidance. In addition, the agency
intends to include the modular review program as a topic for discussion
at future stakeholder meetings.

# **IV. Scope**

The PMA modular review program affords an alternative to the
preparation, submission, and evaluation of traditional premarket
approval applications (PMAs). Because FDA believes that PMA supplements
would rarely be appropriate for modular review, the scope of this
document is limited to applicants pursuing approval of original PMAs.

# **V. Definitions**

[Modular PMA]{.underline} is a compilation of sections or \"modules\"
submitted at different times that together become a complete PMA
application.

[PMA Module]{.underline} is a discrete section of the PMA that can be
submitted and reviewed independently. A module is a set of elements,
tests, information, etc., that addresses a selected aspect of the device
application, such as manufacturing or animal testing.

[PMA Module Amendment]{.underline} is information an applicant submits
to FDA to modify a pending module.

[PMA Module Supplement]{.underline} is information submitted to a closed
module for FDA review of a change or modification to the information
provided in the original module.

[PMA Shell]{.underline} is an outline and description of the contents of
all the modules that will comprise the PMA.

# **VI. User Fee Considerations for Modular Review**

MDUFMA amends the act to provide FDA new responsibilities, resources,
and challenges. One significant provision of MDUFMA permits FDA to
collect user fees for certain premarket reviews (i.e., premarket
approval applications, premarket reports, supplements, premarket
notifications, biologics license applications, and efficacy supplements
as discussed in more detail below) for those applications received on or
after October 1, 2002. On February 20, 2003, enabling appropriations
were enacted, thus allowing the agency to immediately begin to collect
fees for medical device applications. Please see
[h]{.underline}[ttp://www.fda.gov/oc/mdufma](http://www.fda.gov/oc/mdufma)
for information on remitting user fees.

As discussed in previous guidance on user fee payments for modular
PMAs,[^5] the fee for a modular PMA is due upon submission of the first
module. If FDA receives the first module prior to payment, we will place
the file on hold until we receive payment and notify the applicant of
this action by facsimile.[^6] FDA begins its review when the Office of
Financial Management notifies CDRH or CBER that payment has been
received.

# **VII. Industry Instructions for Submitting a Modular PMA** 

### Contact Review Group

> Attachment I contains a flow chart of the steps ordinarily involved in
> modular PMA review. The first step in the modular PMA process should
> be contacting the CDRH Branch Chief within the appropriate review
> division or the applications division in the appropriate CBER Office
> to indicate your intention to submit a modular PMA.[^7] FDA believes
> early interaction with the appropriate branch/division and continued
> communication will optimize the opportunity for success of the modular
> PMA.

## **A. PMA Shell**

#### 1. Determination that PMA Review is Appropriate for the Device 

> Immediately upon receipt of an informal request for modular review,
> the Branch Chief assigns review staff (or other personnel designated
> by the division). That person answers a set of preliminary questions
> (please see **Premarket Approval Application Filing Review; Guidance
> for Industry and FDA**) aimed at ensuring that FDA utilizes the
> appropriate regulatory review path. Depending upon the answers to
> these preliminary questions, regulation as a class III device may be
> inappropriate. If the responses to the preliminary questions indicate
> that review of the modular proposal should not continue, staff
> notifies the applicant using the procedures identified in the guidance
> document referenced above.

#### 2. Content of a PMA Shell

> FDA recommends that applicants use the sample PMA shell (Attachment II
> Sample PMA Shell) as a model when designing PMA shell proposals. In
> your PMA shell proposal, you should describe the contents of each
> module in sufficient detail to provide FDA with a complete
> understanding of the modules you plan to submit. The PMA shell
> proposal should address all elements required under 21 CFR 814.20
> *Application* and the timing of each modular submission.
>
> If the clinical trial period will be lengthy or the product
> development time line is long, you should carefully consider your
> schedule for submitting PMA modules when developing your PMA shell.
> Premature submission of PMA modules (i.e., prior to finalizing your
> device design) could result in changes to the device that require you
> to submit additional data and FDA to re-evaluate closed PMA modules.
>
> FDA may refuse to accept a proposal for a PMA shell if the timing is
> inappropriate. For example, if you are within 6 months or less of
> submitting the final PMA module, FDA believes PMA modular review may
> not be appropriate because it may not allow sufficient time for FDA to
> complete its review of all the modules before receiving the final PMA
> module.
>
> In addition, with the exception of the manufacturing module,
> applicants should not plan to submit PMA modules in close succession.
> The schedule for submitting PMA modules should allow enough time for
> the review division to complete review of one module before the next
> module is received. Submitting PMA modules for concurrent review
> undermines the purpose of the modular review program because the
> agency cannot review multiple modules on an abbreviated cycle. If you
> intend to submit several modules at the same time or in close
> succession, FDA recommends that you submit a traditional PMA.
>
> The exception to this is the manufacturing module, which may be
> submitted at any time, regardless of when other modules were
> submitted. This is appropriate because the Office of Compliance, CDRH
> has primary responsibility for reviewing this data. Similarly, in
> CBER, the manufacturing section is reviewed by the Office of Biologics
> Quality. Therefore, FDA can efficiently concurrently review the
> manufacturing module, while another module is being reviewed. The
> manufacturing information should be submitted as a separate module to
> allow for ease of distribution to and review by the appropriate
> office.
>
> Please notify FDA, [in the form of an amendment to your
> shell]{.underline}, when you anticipate that you are within 90 days of
> submitting your final PMA module, so that FDA can schedule a
> pre-approval Quality System Regulation inspection.

#### 3. Informal Review of the Proposed PMA Shell

> After you contact the appropriate Branch Chief, and it is agreed that
> PMA is the appropriate regulatory path, you should fax or email a
> draft of the proposed PMA shell to the branch chief to allow for
> review and comment on the proposal. The Branch Chief assigns a staff
> member to review the proposed shell. This individual is responsible
> for communicating to you any FDA recommended changes and reaching
> verbal agreement with you on the shell.[^8]

#### 4. Submission of the PMA Shell

> After you reach agreement with FDA on the proposed PMA shell, you
> should submit the finalized shell to the following address, as
> applicable:
>
> PMA Document Mail Center (HFZ-401)
>
> Office of Device Evaluation
>
> Center for Devices and Radiological Health
>
> 9200 Corporate Boulevard
>
> Rockville, MD 20850
>
> Or to CBER at:

Food and Drug Administration

Center for Biologics Evaluation and Research

Document Control Center, HFM-99, Suite 200N

Rockville, MD 20852-1448

> In order to facilitate the log-in process, you should prominently
> identify the name of the review staff member with whom you have been
> interacting in your cover letter. After the FDA receives the PMA shell
> and assigns a unique document control number (shell number), the
> review staff will confirm that the PMA shell is consistent with the
> agreed upon proposal and issue an acceptance letter (usually within 2
> weeks). You may then submit PMA modules for review, according to the
> agreed upon schedule.

### 5. Changes to the Accepted PMA Shell 

> If you need to make changes to the shell after it has been accepted
> (e.g., device design modifications are made that require additional or
> different testing or the number of necessary modules increases or
> decreases), you should submit an amendment to the shell with a
> description of the changes and an explanation of the need for changes.
> After reviewing these changes, FDA may wish to discuss them with you.
> Once verbal agreement has been reached, you should submit the revised
> shell to the appropriate address listed above.

## **B. PMA Modules**

### 1. Submission of Each PMA Module

When submitting a module, you should clearly identify the submission as
a module and reference the previously assigned shell number (and module
number) in the cover letter. As outlined in Attachment II Sample PMA
Shell, you should include the following in every module:

-   cover letter;

-   table of contents;

-   executive summary of the testing and results included in the module;

-   device description and principles of operation; and

-   bibliography (with references only to articles relevant to that
    module).

Duplication of some information between modules is necessary to allow
the review staff assigned to that PMA module to review it in an
efficient manner.

### 2. Incomplete PMA Modules 

The full benefit of PMA modular review to both FDA and the applicant
cannot be realized if PMA module submissions are routinely incomplete.
Therefore, you should complete all testing to support the specific PMA
module before submitting the module to FDA for review. FDA may reject an
incomplete module by issuing a letter to the applicant stating that the
review may not proceed until we receive the missing information. FDA
intends to review each module within a 90-day time period, beginning
upon submission of an amendment containing the balance of the missing
information.

### 3. Time Frame for Reviewing a PMA Module

FDA's objective is to complete the review of each module and issue a
deficiency letter or an acceptance letter within 90 days of receipt of
the module. Deficiency letters notify the applicant of outstanding
issues that need clarification or additional information. Acceptance
letters notify the applicant that all issues have been resolved.

FDA intends to review any amendments responding to a deficiency letter
under a 90-day clock. Submitting any unsolicited major amendment at any
time during the review of the PMA module resets the 90-day clock. Major
amendments are defined in 21 CFR 814.37(c)(1).

### 4. Reopening a Closed PMA Module

If you modify your device after FDA deems a PMA module acceptable, you
should contact the appropriate review division staff to discuss the
modification and any testing needed to support it. You should submit
data generated to support the modification separately to each of the
affected modules with a revised executive summary. FDA logs-in this type
of submission as a supplement to the PMA module. As described above, FDA
intends to issue a deficiency or acceptance letter within 90 days of
receipt of the supplement.

### 5. Submission of the Final PMA Module

> An applicant's submission of the final PMA module (i.e., final
> clinical data, proposed labeling, and summary of safety and
> effectiveness), plus the incorporation by reference of previously
> submitted modules, will complete the modular PMA. You should clearly
> identify the final PMA module submission as the "**COMPLETED MODULAR**
> **PMA"** in the cover letter. You should specifically reference (by
> shell and module numbers) the modules that have been accepted by the
> FDA and also identify any modules with outstanding deficiencies at the
> time of PMA submission. In order for the PMA to be complete, responses
> to all outstanding deficiencies related to previously submitted
> modules should accompany the final PMA module.
>
> Upon receipt of this final PMA module, FDA assigns a PMA number to the
> completed application.

### 6. Filing of the Modular PMA

> Upon receipt of the final module, FDA makes its filing decision. This
> decision is based on whether the last module includes all the
> information necessary to complete the PMA as required by 21 CFR
> 814.20. The PMA Filing guidance[^9] describes the kind of information
> required under this regulation that needs to be submitted before FDA
> can file a PMA. FDA plans to use the information described in this
> guidance in making filing determinations and, as for a traditional
> PMA, generally issues a filing/non-filing letter within 45 days of
> receipt of the last module. If FDA decides to file the PMA, the filing
> date is the date that the application became complete, typically the
> receipt date of the last module. The 180-day \"PMA clock\" under 21
> CFR 814, also begins on that date. If the agency decides not to file
> the PMA, FDA will issue a non-filing letter to the PMA applicant.

# **Attachment I Modular PMA Flow**

# Attachment II Sample PMA Shell

+------------+-------------------------------------------+-------------+
| **Comp     |                                           |             |
| any/Device |                                           |             |
| Name**     |                                           |             |
+------------+-------------------------------------------+-------------+
| **Module   | **Contents**                              | **Projected |
| \#**       |                                           | Date of     |
|            |                                           | S           |
|            |                                           | ubmission** |
+------------+-------------------------------------------+-------------+
| Module 1   | Table of Contents for Module 1            |             |
|            |                                           |             |
|            | Executive Summary[^10]                    |             |
|            |                                           |             |
|            | Device Description and Principles of      |             |
|            | Operation                                 |             |
|            |                                           |             |
|            | Declaration of Conformance to Standards   |             |
|            | for Module 1                              |             |
|            |                                           |             |
|            | Bibliography/References for Module 1      |             |
|            |                                           |             |
|            | Non-clinical Laboratory Studies, for      |             |
|            | example:                                  |             |
|            |                                           |             |
|            | -   Physico-Chemical Testing              |             |
|            |                                           |             |
|            | -   Biocompatability/Toxicity Testing     |             |
|            |                                           |             |
|            | -   Animal/Biological Testing             |             |
+------------+-------------------------------------------+-------------+
| Module 2   | Table of Contents for Module 2            |             |
|            |                                           |             |
|            | Executive Summary\*                       |             |
|            |                                           |             |
|            | Device Description and Principles of      |             |
|            | Operation                                 |             |
|            |                                           |             |
|            | Declaration of Conformance to Standards   |             |
|            | for Module 2                              |             |
|            |                                           |             |
|            | Bibliography/References for Module 2      |             |
|            |                                           |             |
|            | Non-clinical Laboratory Studies, for      |             |
|            | example:                                  |             |
|            |                                           |             |
|            | -   Engineering/Bench Testing             |             |
|            |                                           |             |
|            | -   Sterilization, Shelf Life & Packaging |             |
|            |     Information (Pertinent information    |             |
|            |     should also be provided in the        |             |
|            |     manufacturing section)                |             |
|            |                                           |             |
|            | -   Software Validation and Verification  |             |
|            |     Information                           |             |
+------------+-------------------------------------------+-------------+
| Module 3   | Table of Contents for Module 3            |             |
|            |                                           |             |
|            | Executive Summary\*                       |             |
|            |                                           |             |
|            | Device Description and Principles of      |             |
|            | Operation                                 |             |
|            |                                           |             |
|            | Manufacturing Information                 |             |
|            |                                           |             |
|            | -   Refer to "Quality System Information  |             |
|            |     for Certain Premarket Application     |             |
|            |     Reviews; Guidance for Industry and    |             |
|            |     FDA Staff" (February 2, 2003)         |             |
+------------+-------------------------------------------+-------------+
| Final PMA  | Table of Contents for entire PMA,         |             |
| Module     | including all modules                     |             |
|            |                                           |             |
|            | SSED (i.e., compilation of executive      |             |
|            | summaries)                                |             |
|            |                                           |             |
|            | Clinical Data (including Protocols,       |             |
|            | Results and Analyses)                     |             |
|            |                                           |             |
|            | Financial Disclosure Information          |             |
|            |                                           |             |
|            | Proposed Labeling:                        |             |
|            |                                           |             |
|            | -   Physician Instructions                |             |
|            |                                           |             |
|            | -   Patient Instructions                  |             |
|            |                                           |             |
|            | -   Operation Manuals                     |             |
|            |                                           |             |
|            | Post-marketing Plan (e.g., proposed       |             |
|            | long-term follow up studies, if           |             |
|            | appropriate)                              |             |
|            |                                           |             |
|            | Bibliography/References for the Final PMA |             |
|            | Module                                    |             |
+------------+-------------------------------------------+-------------+

# **Attachment III Frequently Asked Questions**

1.  **What is the "sample Modular PMA Shell"?**

    An example of a sample Modular PMA shell is provided in Attachment
    II of this guidance document. FDA recommends that you follow this
    model whenever possible. Ideally, there should be no more than 3-4
    modules. However, we understand that there may be instances when the
    recommended model is not suitable and should be modified. The review
    staff will work with you to establish a shell that is acceptable to
    both parties.

2.  **What should I consider when deciding whether to submit a Modular
    PMA?**

FDA recommends that you carefully consider the time line for the
development of your product and your commitment to pursuing FDA approval
when deciding whether to submit a modular PMA. FDA may refuse to accept
a PMA shell proposal if timing is inappropriate. For example, if you are
within 6 months or less of submitting the final PMA module, FDA believes
PMA modular review may not be appropriate. Submitting a PMA shell
proposal within 6 months or less of submitting the final module does not
allow sufficient time for FDA to complete its review of all the modules
before receiving the final module.

If the clinical trial is lengthy or the product development time line is
long, you should carefully consider your schedule for submitting PMA
modules when developing the PMA shell. Premature submission of PMA
modules could result in changes that require re-evaluation of closed PMA
modules.

3.  **What is an appropriate length of time between submission of
    modules?**

You should provide the approximate timing of the submission of each PMA
module in the PMA shell to FDA. It is FDA's intent that applicants who
choose to participate in the PMA Modular Review Program would submit
modules at intervals that will allow the agency enough time to review
the module, provide feedback, and close out the module prior to the
arrival of the next module. The one exception is the manufacturing
module, which may be submitted without regard to the timing of
submission of other module(s). In CDRH, the Office of Compliance is the
primary reviewer of this module, while in CBER, both the Office of
Biologics Quality and the product office review[^11] the manufacturing
module.

4.  **What should I include with each module?**

You should include the following in each PMA module:

-   cover letter;

-   table of contents;

-   executive summary of the testing and results included in the module;
    and

-   bibliography.

In addition, you should submit complete information for each module,
i.e., all testing should be finished and the results provided, which
will enable FDA to review the data and make a decision. If the PMA
module is incomplete, FDA may refuse to accept the PMA module for
review.

**5. What happens to the outstanding modules when I submit my final PMA
module?**

You should address any outstanding deficiencies from previously
submitted modules when you submit the final PMA module. Once you submit
the final PMA module, FDA considers the PMA shell and its modules closed
and makes its filing decision.

**6. When do I have to pay the user fee for a Modular PMA?**

The fee for a modular PMA is due upon submission of the first
module.[^12] If FDA receives the first module prior to payment, we will
place the file on hold until we receive payment[^13] and notify the
applicant of this action by facsimile. The 90 day review clock for the
first module starts on the date that FDA's Office of Financial
Management notifies CDRH or CBER that payment has been received.

[^1]: Section 515(c) of the act, as amended by section 209 of MDUFMA.

[^2]: This guidance was issued on February 25, 2003 and can be found at
    [www.fda.gov/cdrh/mdufma/guidance/1201.html](http://www.fda.gov/cdrh/mdufma/guidance/1201.html)
    (hereinafter referred to as the Assessing User Fees guidance.)

[^3]: This guidance can be found on the CDRH website at:
    <http://www.fda.gov/cdrh/mdufma/guidance/1201.html>.

[^4]: This letter can be found at:
    [www.fda.gov/cdrh/mdufma/pgoals.html](http://www.fda.gov/cdrh/mdufma/pgoals.html).

[^5]: "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"
    can be found at:
    [www.fda.gov/cdrh/mdufma/guidance/1201.html](http://www.fda.gov/cdrh/mdufma/guidance/1201.html)

[^6]: Section 209 of MDUFMA authorizes FDA to put the application on
    hold until payment is received.

[^7]: For assistance in identifying the appropriate review branch, 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]{.underline}](http://www.fda.gov/cber/inside/orgover.pdf).

[^8]: If agreement cannot be reached with the review staff assigned to
    review the shell within 30-days, please contact branch/division
    management.

[^9]: See "Premarket Approval Application Filing Review" at
    [www.fda.gov/cdrh/ode/guidance/297.html](http://www.fda.gov/cdrh/ode/guidance/297.html)

[^10]: ^^ Executive Summary should contain a summary of the testing and
    results provided in the module.

[^11]: Please discuss with the appropriate regulatory project management
    branch in CBER.

[^12]: "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"
    can be found at:
    [www.fda.gov/cdrh/mdufma/guidance/1201.html](http://www.fda.gov/cdrh/mdufma/guidance/1201.html)

[^13]: See section 515(c)(3)(A) of the act.