Contains Nonbinding Recommendations  
FDA and  Industry  Actions on  
Premarket Approval  Applications  
(PMAs):  Effect on  FDA Review   
Clock and Goals  
 
Guidance  for Industry and  
Food and Drug Administration Staff  
 
Document  issued on  October 3, 2022.  
 
Document originally issued  on  October 8,  2003.  
 
This document supersedes FDA  and  Industry  Actions  on  Premarket Approval  
Applications  (PMAs): Effect on FDA  Review Clock  and  Goals   
issued  October 2, 2017.  
 
For questions about this document regarding CDRH-regulated devices,  contact  the  Office of 
Regulatory Programs/Division of Submission Support/PMA, HDE,  Q-Submission, and Device  
Tracking Lifecycle Team  at 301-796-5640,  or by email at  
OPEQSubmissionSupport@fda.hhs.gov. For questions about this document regarding CBER-
regulated devices, contact the Office of Communication, Outreach, and Development (OCOD)  at  
1-800-835-4709 or 240-402-8010, or by email at  ocod@fda.hhs.gov.  
 
 
 
 
 
 
 
 
 
 
      U.S.Department of Health and Human Services  
  FOOD & DRUG  Food and Drug Administration  
  Center for Devices and Radiological Health  
ADMINISTRATION 
Center for Biologics  Evaluation and Research   Contains Nonbinding Recommendations  
 
Preface  
 
Public Comment  
 
You may submit  electronic comments and suggestions at any time for Agency consideration to 
https://www.regulations.gov. Submit written comments to  the Dockets Management  Staff, Food 
and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 20852-
1740. Identify all comments with  the docket number  FDA-2003-D-0378. Comments may not be  
acted upon by the Agency until the document is next  revised or updated.  
 
Additional Copies  
 
CDRH  
Additional copies are  available from the  Internet. You may also send an email request to 
CDRH-Guidance@fda.hhs.gov to receive  a copy of the guidance. Please include the document  
number 1208 and complete title of the guidance  in the  request.  
 
CBER  
Additional copies are  available from the  Center  for  Biologics Evaluation and  Research  (CBER),  
Office of Communication, Outreach, and Development (OCOD), 10903 New Hampshire  Ave., 
WO71, Room 3128, Silver Spring, MD 20993-0002, or by calling 1-800-835-4709 or 240-402-
8010, by email, ocod@fda.hhs.gov, or from the  Internet at   
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-
information-biologics/biologics-guidances.   Contains  Nonbinding Recommendations  
 
  
 
Table of Contents  
 
I.   Introduction  .............................................................................................................................  1  
II.   Scope  .......................................................................................................................................  2  
III.   FDA Actions  ........................................................................................................................  2  
A.   Approval Order.....................................................................................................................  3  
B.   Approvable Letter.................................................................................................................  3  
C.   Major  Deficiency  Letter  .......................................................................................................  4  
D.   Not  Approvable  Letter ..........................................................................................................  4  
E.   Denial  Order  .........................................................................................................................  5  
F.   Acknowledgement  of  Voluntary Withdrawal .......................................................................  5  
IV.   PMA Performance Goals for MDUFA  IV ...........................................................................  6  
V.   PMA Performance Goals for MDUFA V ................................................................................  7  
A.   Submission  ...........................................................................................................................  7  
B.   Acceptance and Filing Review for  Original PMAs and Panel-Track Supplements .............  8  
C.   Substantive Review for  Original PMAs, Panel-Track Supplements and 180-Day  
Supplements  .........................................................................................................................  8  
D.   MDUFA V Goals  .................................................................................................................  9  
E.   Missed MDUFA Decision Communication for Original PMAs and Panel-Track  
Supplements  .......................................................................................................................  10  
VI.   Applicant Actions  ..............................................................................................................  10  
A.   Unsolicited Major  Amendment  ..........................................................................................  11  
B.   Solicited  Major  Amendment  ..............................................................................................  11  
C.   Unsolicited Minor  Amendment  ..........................................................................................  12  
D.   Response  to  Interactive  Review Request ............................................................................  12  
E.   Withdrawal of  an Application  ............................................................................................  12  
  Contains Nonbinding Recommendations  
 
 
FDA and Industry Actions on 
Premarket  Approval  Applications  
(PMAs): Effect on FDA Review  
Clock and Goals  
 
 
Guidance  for Industry and  
Food and Drug Administration Staff   
 
This guidance represents the current thinking of the  Food and Drug Administration (FDA  
or Agency) on this topic. It does  not establish any rights for any person and is not binding  
on  FDA or the public. You can use an alternative approach if  it  satisfies the requirements  
of the applicable statutes and regulations. To discuss an alternative approach, contact the  
FDA staff or Office responsible for this guidance as  listed on the title page.  
I.   Introduction  
 
The Medical Device  User Fee  Amendments of 20221 (MDUFA  V), amended the Federal 
Food, Drug, and Cosmetic Act  (the  FD&C Act) to authorize FDA to  collect user fees for  the  
review of certain premarket submissions  received on or  after October 1, 2022, including 
premarket  approval applications (PMAs).  The additional funds obtained from user  fees  will 
enable FDA, with the cooperation of industry, to improve the device  review process to meet  
certain performance  goals and implement improvements for the medical device  review 
process.  
 
Performance  goals were negotiated and agreed to under  MDUFA V  for PMAs received  in  FY  
2023-2027.  These performance goals and process improvements  are outlined in the letter  
from the Secretary of Health  and Human Services to Congress2  (MDUFA  V  Commitment  
Letter) and are further described below.  
 
In general, FDAs guidance documents do not establish legally enforceable  responsibilities. 
Instead, guidances describe the Agencys current thinking on a topic and should be viewed 
only as recommendations, unless specific regulatory or statutory requirements are cited. The 
 
1  See Title II of the FDA  User Fee  Reauthorization Act of  2022  (Public  Law 117-180).  
2  See 168 CONG. REC. S5194-S5203 (daily ed. September 28, 2022)  (Food and Drug Administration User  Fee 
Reauthorization).  The MDUFA V Commitment Letter is  also  available  at 
https://www.fda.gov/media/158308/download.  
  1  Contains Nonbinding Recommendations  
 
 
use of the word should in Agency guidances means that something is suggested or  
recommended, but not required. 
II.   Scope  
This  guidance document describes:  
 
   the different FDA actions that  may be taken on premarket  approval applications  
(PMAs);  
 
   the effect each action has on goals under MDUFA IV (for PMAs received in FY 2018 
 2022);  
 
   the effect each action has on goals under MDUFA V (for PMAs received in FY 2023 
 2027); and  
 
   the different industry actions that  may be taken on PMAs.  
III.   FDA Actions  
The PMA regulation outlines the various  actions  FDA may take  on an original PMA or PMA  
  
supplement during the course of our  review.3  For original PMAs, panel-track supplements, 
 
and 180-day supplements,4 the following responses are considered FDA  actions:  
 
   approval order;  
   approvable letter;  
   major deficiency letter;  
   not approvable letter; and  
   denial order.  
 
For real-time supplements, all of the above responses apply with the exception of a major 
deficiency letter.  
 
Furthermore, of these FDA actions, all but a major deficiency letter are a MDUFA decision 
under  FDAs commitment letters and are measured against a MDUFA  IV/V goal.    These 
FDA actions are described below.  
 
 
3  See 21 CFR Part  814, Subpart C.  
4  For more  detailed information, see FDAs guidance document, User Fees and Refunds for Premarket  
Approval Applications and Device Biologics Licences Applications, available at  
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/user-fees-and-refunds-premarket-
approval-applications-and-device-biologics-license-applications  or  the guidance  document entitled,  
Modifications to Devices Subject to Premarket Approval (PMA)  - The PMA Supplement Decision-Making 
Process, available at  https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/modifications-devices-subject-premarket-approval-pma-pma-supplement-decision-making-process.  
  2  Contains Nonbinding Recommendations  
 
 
A.   Approval Order  
 
FDA will  issue  an approval order  (letter) informing  the  applicant  that the  PMA is approved 
and that the  applicant may  begin  commercial distribution of  the  device  in accordance  with  
any  prescribed conditions of  approval after  we  have  completed our  review  and:  
 
   none  of  the  reasons listed in 21  CFR 814.45 for  denying  approval applies;  
 
   there  is reasonable  assurance  the  device  is safe  and  effective  (using  the  criteria 
provided in 21 CFR 860.7)  for its intended use  as  prescribed in the  product labeling; 
and  
 
   the  device  manufacturing facilities, methods, and  controls were  found to be  in 
compliance  with the  Quality  System  regulation (21  CFR Part  820).  
 
An  approval order  shuts  off  the  review clock,  marks  the  end  of  FDA review,  and is  considered 
a  final  action.  
 
B.   Approvable Letter  
 
FDA will  issue  an approvable  letter  informing  the  applicant that we  have  completed our  
review of  the  application and determined that  there  needs to be:  
 
   resolution of  minor  deficiencies,5  which are  identified in  the  approvable  letter  
(21CFR 814.44(e));  and/or  
 
   completion of  an FDA inspection that finds  the  manufacturing facilities,  methods, and 
controls in compliance  with the  Quality  System (QS)  regulation, 21 CFR Part  820, 
and, if  applicable, verifies records  pertinent  to the  PMA as per  21 CFR  
814.44(e)(1)(iii).   When this is the  case, the  approvable  letter  states that the  device  is  
approvable  pending  GMP  inspection.  
 
When FDA issues an  approvable  letter  pending resolution of  minor  deficiencies, we  stop the  
review  clock and  place  the  application on hold.   When FDA receives a  complete response  to 
an  approvable  letter, we  will resume  the  clock with a  new  FDA  response timeframe  to reach a 
final decision.   FDA will issue a decision within 60  calendar  days of the sponsors response  
to the  approvable letter, as resources permit, but not to the detriment of meeting the  
quantitative review timelines and statutory obligations.   
 
When FDA issues an  approvable  pending  GMP  inspection letter, we  stop the  review clock.   
Once  FDA determines that the  device  manufacturing facilities, methods, and  controls  are  
 
5  Minor deficiencies may include, for example, clarifications  of previously submitted information, revisions to 
the labeling, and revisions/development of a post approval study protocol.  
  3  Contains Nonbinding Recommendations  
 
 
found to be in compliance  with the  Quality System  regulation, 21 CFR part  820, we  will 
issue  an approval order.  
 
C.   Major  Deficiency  Letter  
 
FDA will  issue a major deficiency letter6  informing the applicant that the  PMA lacks  
significant information necessary for  FDA to  complete our  review and requests the applicant  
to amend the application to provide the necessary information regarding the device (21 CFR 
814.37(b)), such as:  
 
   a detailed re-analysis of  previously submitted data  (e.g., alternative statistical  
method);  
 
   additional test data to demonstrate safety and effectiveness of the device (e.g., 
electromagnetic compatibility, electrical safety, biocompatibility, reliability, software, 
labeling, animal testing, sensitivity and specificity in a certain population);  
 
   scientific  rationale for test data  critical to  determining  reasonable  assurance of  safety  
and  effectiveness of the  device provided in the  submission; or  
 
   new validation data and analyses  (e.g., due  to device modifications made during the  
course of the PMA review). 
 
When FDA issues a major deficiency letter, we  stop the  review  clock and place the 
application on hold.  Because a major deficiency letter  is not a  MDUFA decision, when FDA 
receives a  complete  response  to a major deficiency letter, we  will resume  the clock and our  
review with a goal of  reaching a  MDUFA  decision within  the  remaining time  of the  
applications  review  track (e.g., 180 FDA days7). 
 
D.   Not  Approvable Letter 
 
FDA will  issue a not approvable letter  informing the applicant that we have  completed our  
review  and that we do not believe  that the application can be approved because of significant  
deficiencies.   The not approvable letter  will describe the deficiencies in the application, 
including each applicable ground for  not approving and, where practical, will identify 
measures required to place the submission in approvable form (21 CFR 814.44(f)). 
 
 
6  For additional information about deficiencies, see FDAs guidance document, Developing and Responding to 
Deficiencies in Accordance with the Least Burdensome Provisions,  available at  
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/developing-and-responding-
deficiencies-accordance-least-burdensome-provisions.  
7  As described in Section VIII.C  of the MDUFA V Commitment Letter, FDA Days are those calendar days  
when a submission is considered to be  under review at the Agency for submissions that have been filed. See 
Section VIII.C  of the MDUFA V Commitment Letter, available at 
https://www.fda.gov/media/158308/download.  
  4  Contains Nonbinding Recommendations  
 
 
Generally, before  FDA issues a  not  approvable  letter, we  will  first  issue  a  major  deficiency  
letter  to provide  the  applicant with  an  opportunity  to address our  concerns.  However, if  an 
applicant  fails to provide  an adequate  response to a  major  deficiency letter, or if we have 
attempted to resolve all deficiencies via interactive review and have not received adequate 
responses, FDA  will issue  a  not  approvable  letter.  
 
When FDA issues a  not  approvable  letter,  we  stop the  review clock and place  the application 
on hold.   When FDA  receives a  complete  response  to a  not  approvable  letter,  we  will resume  
the  clock  with a  new FDA response  timeframe.   Although not a  performance goal,  FDA 
intends to review a  complete  response  to a  not  approvable  letter  within 180  calendar  days.  
 
E.   Denial  Order  
 
FDA will  issue  a  denial order  (letter) when  we  need to inform the  applicant that we  have 
denied approval of the  application.   The  denial order  will identify  all deficiencies in the  
application, including  each applicable  ground for  denial under  section 515(d)(2)  of  the  
FD&C  Act and, where  practical, will  identify  measures required to place  the  application in 
approvable form  (21 CFR 814.45).   The  denial order  will include  a  notice  of  an opportunity  
to request  review under  section 515(d)(4)  of  the  FD&C  Act.   FDA  may  deny  approval of  a  
PMA for any  of the  reasons identified in 21 CFR 814.45(a).  
 
When FDA issues a  denial order,  we  shut off  the  review  clock if  a  prior  action has not  
already  done  so.   FDA expects that a denial will  normally be preceded by another FDA  
action that stops the review clock, such as a not approvable letter.  There is, however, no 
statutory requirement for any prior FDA action, and FDA may, in appropriate circumstances, 
proceed directly to issue  a denial order.   A  denial order  marks  the  end  of FDAs review,  as  
this  is  considered a  final  action.  
 
F.   Acknowledgement  of  Voluntary Withdrawal  
 
Under  the  PMA regulation, FDA considers an original PMA or  PMA supplement to have 
been voluntarily  withdrawn if  an applicant  fails to  respond to an approvable, major 
deficiency, not  approvable, or not filing  letter  within 180 calendar  days  (21 CFR 814.44(g)).  
FDA will automatically  grant  one  180-day  extension to respond to one  of  these four  FDA 
action letters,  increasing  the  time  to provide  a  complete  response  to the  FDA action letter  to a  
total of  360 calendar  days.   FDA intends  to  notify  the  applicant when 360 calendar  days have  
elapsed with a  letter  acknowledging  voluntary  withdrawal  of  the  PMA  or  PMA supplement. 
Any  amendment submitted in response  to an FDA action letter  after  360 calendar  days  will 
be  considered  a  resubmission of  the  PMA.   As  such, it will be  assigned  a  new PMA number, 
will be  subject to the  requirements of  21 CFR 814.20, and the  applicant must pay  a  new user  
fee.  
 
 
 
  5  Contains Nonbinding Recommendations  
 
 
IV.   PMA  Performance Goals for  MDUFA  IV   
The performance goals for PMA applications  received in  FY 2018 through FY 2022 were  
defined in the  MDUFA  IV  Commitment  Letter.8  Performance  goals and associated changes 
introduced under  MDUFA III and retained  in  MDUFA  IV  include:  
 
   most PMA submissions  are subject to a user fee, and all PMA submissions  need a 
 
valid  eCopy9 in order  to initiate  review;  
 
   original PMAs and panel-track supplements will undergo an acceptance  review that 
precedes the filing review10;  
 
   original PMAs, panel-track supplements, and 180-day supplements are subject to a  
Substantive Interaction goal;  
 
   original PMAs, panel-track supplements, 180-day supplements, and real-time 
supplements  are subject to one-tier  MDUFA decision goals  (modular PMAs no longer  
have a  MDUFA performance  goal);  
 
   the terms expedited  and priority  will  now be referred to as breakthrough devices 
(to be consistent with  the statutory language  in the  21st  Century Cures Act11)  and 
PMAs with that designation will no longer be analyzed as a separate cohort; instead 
the cohorts will be based on whether or not  a panel meeting  occurs;  
 
   there  is a  shared outcome goal for the total time from  receipt of  a submission accepted  
for filing review  to decision for  originals and panel track supplements; and 
 
   for original PMAs and Panel-Track PMA supplements for  which the MDUFA 
decision is  exceeded by 20  calendar  days,  FDA  will send a  Missed MDUFA decision 
(MMD) communication to the applicant.  
 
Performance  goals and associated changes introduced under  MDUFA  IV  include:  
 
   for  submissions that require Advisory Committee input, FDA will issue a  MDUFA  
decision within 60 calendar  days from  the Advisory Committee recommendation, as  
 
8  See 163 CONG. REC. S4729-S4736 (daily ed. August 2, 2017)  (Food and Drug Administration User Fee  
Reauthorization).  The MDUFA IV Commitment Letter is  also available at 
https://www.fda.gov/media/102699/download.  
9  For additional information,  refer to the  guidance document,  eCopy Program for Medical  Device  
Submissions, available at  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ecopy-
program-medical-device-submissions.  
10  For additional information on the acceptance and filing reviews, refer to the  guidance document, Acceptance  
and Filing Reviews for Premarket Approval Applications (PMAs), available at  
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/acceptance-and-filing-reviews-
premarket-approval-applications-pmas.  
11  See the 21st  Century Cures Act  (Public Law 114-255).  
  6  Contains Nonbinding Recommendations  
 
 
resources permit, but not to the detriment of meeting the quantitative review timelines  
and statutory obligations; and 
 
   for submissions that receive a MDUFA decision of Approvable, FDA  will issue a  
decision within 60 calendar  days of the sponsors response to the approvable letter, as  
resources permit, but not to the detriment of meeting the quantitative review timelines  
and statutory obligations.  
 
V.   PMA  Performance Goals for  MDUFA  V   
The performance goals for PMA applications  received in  FY 2023 through FY 2027 are  
defined in the  MDUFA  V  Commitment  Letter.12  The performance goals and associated  
changes  included in Section IV of this guidance  are also retained in MDUFA V.  
Performance  goals and associated changes introduced under  MDUFA  V  include:  
 
   for original PMA  and  panel-track  supplement  submissions received in FY 2023 
through FY 2024, the average shared outcome Total Time  to Decision goal  for FDA  
and industry is 290 calendar days; and  
 
   for original PMA  and  panel-track  supplement submissions received  in FY 2025  
through FY  2027, the  average  shared outcome Total Time to Decision goal  for FDA  
and industry is 285 calendar days.  
 
A.   Submission  
 
Many PMA submissions  will be subject to a user fee13 and all PMA submissions (originals, 
supplements, reports,  and amendments)  will be  subject to the  requirement  for an eCopy  or an 
electronic submission (eSubmission) using an electronic submission template (e.g., eSTAR  
(electronic Submission Template And Resource )),14,15  when available.   PMA submissions 
will not be  completely processed and distributed and the  review clock will not start without  
confirmation of user fee  payment, if applicable, and a valid  eCopy  or eSTAR. FDA is  
authorized by section 745A(b)(1) of the  FD&C Act to implement eCopy requirements for  
PMA submissions and is  authorized by section 745A(b)(3) of the  FD&C Act to implement  
requirements for submissions solely in electronic format. Please see the guidance entitled  
 
12  https://www.fda.gov/media/158308/download  
13  See   User Fees and Refunds  for Premarket Approval Applications and Device Biologics  License  
Applications, available at  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/user-
fees-and-refunds-premarket-approval-applications-and-device-biologics-license-applications.  
14  eSTAR is the only type of electronic submission template that is intended to be available to facilitate the  
preparation of PMA submissions as eSubmissions. For simplicity, the electronic submission created with this  
electronic submission template is often referred to as an eSTAR.  
15  See FDAs website regarding the eSTAR program, available at  https://www.fda.gov/medical-devices/how-
study-and-market-your-device/voluntary-estar-program.  This website provides current information regarding 
the  eSTAR program  for CDRH and CBER.  
  7  Contains Nonbinding Recommendations  
 
 
eCopy Program for Medical Device Submissions,16 for more information about eCopy 
requirements and the guidance Providing Regulatory Submissions for Medical Devices in 
Electronic Format  Submissions Under Section 745A(b) of the  Federal  Food, Drug, and 
Cosmetic Act17 for more information about eSubmission requirements.   
 
B.   Acceptance and Filing  Review  for  Original  PMAs and  
Panel-Track Supplements  
 
FDA will conduct  an administrative  review to determine  whether the  required elements are 
present in the application.18  If not present, the PMA  review process will not continue and the  
applicant will be notified in writing  that the PMA  is incomplete.   This  finding will be  
communicated to the applicant  within 15 calendar days  of receipt of the application.  This  
communication represents a preliminary review of the application and is not indicative  of 
deficiencies that may be identified later  in the review cycle.  The application will be placed 
on hold and the  review  clock will not start  until the  required elements are provided.  The date  
FDA receives the  amendment containing the  required elements will be the  new PMA receipt 
date for purposes  of placing the application under  review  so that a filing review can proceed.  
The filing review will take place within 45 calendar  days of receipt of the  accepted 
application.  For additional information, please refer to the guidance Acceptance and Filing 
Reviews for  Premarket Approval Applications (PMAs).19  
 
C.   Substantive Review  for  Original PMAs,  Panel-Track 
Supplements and 180-Day  Supplements  
 
Once the application is  filed, FDA should conduct  the substantive  review  and communicate 
with the applicant through a  Substantive  Interaction  within 90 calendar days of the filing  
date.  The Substantive Interaction communication  can be  a major deficiency letter or an email  
indicating  that  FDA will continue to resolve any outstanding deficiencies via  Interactive  
Review.   An  approval or approvable letter  issued prior to the Substantive  Interaction goal 
date  will also qualify as a  Substantive Interaction  for purposes of meeting the  MDUFA  V  
goal.   After a Substantive  Interaction, FDA intends  to work with the applicant via  
Interactive  Review to  reach a MDUFA decision.  
 
 
 
 
16  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ecopy-program-medical-device-
submissions  
17  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/providing-regulatory-
submissions-medical-devices-electronic-format-submissions-under-section-745ab  
18  In the case of a government closure during the  15-day review period, the review  period may be extended by a  
comparable  number of business days that the FDA buildings are closed. If the  applicant  receives an automated  
notice that the acceptance review was not completed  because the screening  period has exceeded 15  calendar  
days, FDA may send a correction notice to the  applicant.  
19  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/acceptance-and-filing-reviews-
premarket-approval-applications-pmas   
  8  Contains Nonbinding Recommendations  
 
 
D.   MDUFA V  Goals  
 
MDUFA  V  includes  goals for  Substantive  Interaction, MDUFA decision, and Total  Time to 
Decision  (see Tables  1 and 2). 
 
The goals for Substantive Interaction  and MDUFA decision are in terms of  FDA  Days, which 
are defined in the  MDUFA  V  Commitment  Letter as those calendar days  when a submission 
is considered to be  under  review at the  Agency for  submissions that have been filed.  FDA 
Days begin on the date of receipt  of the submission or the amendment to the submission that 
enables the  submission to  be  filed.  
 
The shared outcome goal of Total Time to Decision was retained for  MDUFA  V, and is  
defined as the time spent  by FDA reviewing the  application as well as the time spent by the  
applicant responding to questions from FDA.  For MDUFA V, the  Total Time to Decision is  
the number of  calendar days from the date  of  receipt of  a filed submission to a  MDUFA 
decision.  The average  Total Time to Decision for PMA applications is  calculated as the  
three-year rolling  average of the annual Total Time to Decision for applications  (for example, 
for FY 2023, the average  Total Time to Decision for PMA applications would be the average  
of FY 2021 through FY 2023)  within a  closed cohort, excluding the highest  5% and the  
lowest 5% of values.  A  cohort is  closed when 95% of the applications have  reached a  
decision.  
 
MDUFA V includes the following performance goals:   
 
Table 1: MDUFA V  Decision Goals  
 
Substantive Interaction  
  FDA Days   FY2023    FY2027  
 
Original PMAs, Panel-Track   90   95%  
Supplements, and 180-Day   
 
Supplements  
 
MDUFA Decision  
  FDA  Days   FY2023    FY2027  
 
Original  PMAs  and Panel-Track   180   90%  
Supplements - Without  Panel    
 
Original  PMAs  and Panel-Track   320   90%  
Supplements - With Panel    
 
180-Day  Supplements   180   95%  
 
Real-Time Supplements   90   95%  
 
 
 
  9  Contains Nonbinding Recommendations  
 
 
 
 
Table 2: MDUFA V Total Time Goals  
 
Average  Total  Time  to Decision  
  FY2023   FY2024   FY2025   FY2026   FY2027  
Original  PMAs  and   290   290   285   285   285  
Panel-Track Supplements   (275)20   (275/270)21  
 
 
E.   Missed MDUFA Decision Communication for  Original  
PMAs and  Panel-Track  Supplements  
 
For all PMA original and  panel-track supplements  that do not  reach a  MDUFA decision by 
20 calendar days  after the applicable FDA Day goal,  FDA  will provide  a missed MDUFA  
decision communication, which is  written feedback to the applicant to be  discussed in a  
meeting  or teleconference, including the major  outstanding review topic areas or other  
reasons that are preventing  FDA from reaching a decision  as well as an estimated date of  
completion.  
VI.   Applicant Actions  
 
Actions taken by an applicant  may include the  submission of an unsolicited  major  
amendment, submission of a solicited major amendment, submission of a minor amendment, 
or  withdrawal of the application (either  by letter or by not responding to an FDA request).22   
The  information below clarifies the basis for  each action an applicant may take and the  effect 
each action has on the  review clock and review  goals.  
 
As with the original PMA, any amendment to a PMA or a request to withdraw a  PMA  will 
need to include an eCopy or eSTAR  (when available) for the submission to be processed as  
described in the guidance documents, eCopy Program for Medical Device Submissions.23  
 
20  The goal will be adjusted if the conditions of Section III.A of the MDUFA V Commitment Letter are met. For  
additional information, see Section III.A  of the MDUFA V Commitment Letter, available  at 
https://www.fda.gov/media/158308/download.  
21  The goal will be adjusted if the conditions of Section III.A of the MDUFA V Commitment Letter are met. For  
additional information, see Section III.A  of the MDUFA V Commitment Letter, available  at 
https://www.fda.gov/media/158308/download.  
22  See 21 CFR 814.37.  
23  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ecopy-program-medical-device-
submissions   
  10   Contains Nonbinding Recommendations  
 
 
and Providing Regulatory Submissions for Medical Devices in Electronic Format  
Submissions Under Section 745A(b) of the  Federal Food, Drug, and Cosmetic Act.24, 25   
 
A.   Unsolicited Major  Amendment  
 
An unsolicited major amendment is a  submission of substantial new data by the applicant, on 
an applicants own initiative, to be  added to a  pending original or panel-track supplement  PMA 
submission.  Typical  situations  that  may prompt  an applicant  to  submit  an  unsolicited major 
amendment  include:  
 
   the applicant obtains additional test data  related to the safety or  effectiveness of the  
device, or the applicant becomes  aware of data  that was omitted from the original 
application (e.g., electromagnetic compatibility, electrical safety, biocompatibility, 
reliability, software, labeling, animal testing);  
 
   the applicant obtains significant new clinical data  from  a previously unreported study, 
or obtains updated data  from  a previously reported study; or  
 
   the applicant obtains new  validation data and analyses (e.g., concerning device  
modifications made by the applicant during the course of the  PMA review).  
 
Unsolicited major amendments should not be used to add new device models or components  
of the device during the course of the PMA review.  The submission of an unsolicited major  
amendment by the  applicant extends the  time  allotted to reach a FDA decision goal (i.e., 
MDUFA  decision  as defined MDUFA IV  and V  Commitment Letters) as follows:  
 
   if the applicant submits  an unsolicited major amendment prior to the Substantive  
Interaction, the FDA decision goal date  is  extended by the number of FDA  days that 
 
have elapsed, i.e., between receipt of the application and receipt of  the amendment; or  
 
   if the applicant submits  an unsolicited major amendment  after the Substantive  
Interaction, the FDA decision goal date  is extended by the number of days equal to  
75% of the difference between the filing date and the date of receipt of the  
amendment, i.e., 75% of the FDA days elapsed  as of the  receipt of the amendment.  
 
B.   Solicited Major  Amendment  
 
A solicited major amendment is the  formal submission of  information by the applicant, at the  
request of FDA (i.e., in response to a  major deficiency or not approvable letter).  The  
applicant submits a  major amendment to FDA when the applicant receives:  
 
 
24  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/providing-regulatory-
submissions-medical-devices-electronic-format-submissions-under-section-745ab  
25  https://www.fda.gov/about-fda/center-biologics-evaluation-and-research-cber/regulatory-submissions-
electronic-and-paper-format-cber-regulated-products   
  11   Contains Nonbinding Recommendations  
 
 
   a major deficiency letter  requesting additional information; or  
   a not approvable letter  that identifies the deficiencies to which the applicant must  
satisfactorily  respond in order  to  place the PMA in  approvable form. 
 
The submission of a solicited major amendment that is a complete response  resumes the 
review  clock upon receipt.   A partial response to  an action letter does  not  resume  the review  
clock.  Although a response to an approvable letter is not considered a major amendment  
because the issues are minor in nature, it will resume the review  clock upon receipt.  A 
partial response to an approvable letter  will not  resume  the review  clock.  
 
C.   Unsolicited Minor Amendment  
 
A minor amendment is  an amendment that contains clarification of previously submitted data  
or additional information of a minor nature.  It is submitted by an applicant  on its own 
initiative.  The  submission of  a minor amendment has no effect on the  review clock. 
 
D.   Response  to  Interactive  Review Request  
 
All responses to  Interactive Review requests should be  submitted via email; however, in 
circumstances where  that  is not possible  (e.g., due to electronic file  size  limitations), a 
response to an interactive  review request that is submitted formally will have no effect on the  
review  clock.  A response to an interactive  review request should only be  submitted once.  
  
E.   Withdrawal of an Application  
 
An  applicant may, on its own  initiative, withdraw a PMA submission at any  time prior to 
approval, and for any reason, by submitting  an amendment informing FDA of  its intent to 
remove the application from  FDAs review.  A withdrawal  action will  stop the review  clock 
on the  receipt  date  of the amendment. FDA will treat  the  withdrawal  as  a final  FDA  action 
that  satisfies  the  decision  goal  for that  submission. 
 
In  addition, as  stated in  Section  III.F  above, FDA considers  an original  PMA  or PMA 
supplement  to have  been voluntarily withdrawn  if an applicant  fails  to  respond  to an 
approvable, major  deficiency, or not  approvable  letter  within  a  total  of 360 calendar  days.  
  12