Contains Nonbinding Recommendations 
 
Procedures for Handling 
Post-Approval Studies Imposed by 
Premarket Approval Application 
Order 
 
Guidance for Industry and Food and 
Drug Administration Staff 
 
 
Document issued on October 7, 2022. 
 
The draft of this document was issued on May 27, 2021. 
 
For questions about this document, contact OPEQ: Office of Product Evaluation and Quality / 
OCEA: Office of Clinical Evidence and Analysis / Division of Clinical Science and Quality via 
email at MandatedStudiesPrograms@fda.hhs.gov. 
 
This guidance supersedes Procedures for Handling Post-Approval Studies 
Imposed by PMA Order, issued on June 15, 2009. 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health 
     
  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. Identify all comments with the docket number FDA-2005-D-0027. 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. You may also send an e-mail request to 
CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance. Please include the document 
number 19043 and complete title of the guidance in the request.   Contains Nonbinding Recommendations 
 
 
 
 
 
 
Table of Contents 
  Introduction ...................................................................................................................... 4 
  Background ...................................................................................................................... 5 
  Post-Approval Study Requirements in PMA Approval Orders .................................. 6 
  Post-Approval Study Protocols ....................................................................................... 7 
 Recommended Elements in a Post-Approval Study Protocol ...................................... 7 
  Post-Approval Study Protocol Review ........................................................................ 8 
  How to Submit Changes to an Approved Post-Approval Study Protocol .................... 9 
 What Happens if the Sponsor and FDA Cannot Complete the Development of a Post-
Approval Study Protocol ................................................................................................ 9 
  When and How to Submit Post-Approval Study Reports .......................................... 10 
  Content and Format of Interim and Final Post-Approval Study Reports ............... 11 
 General Information ................................................................................................... 11 
  PAS Enrollment Status Reports ................................................................................. 12 
  PAS Progress Reports ................................................................................................. 13 
 Final Post-Approval Study Status Reports ................................................................. 14 
  Evaluation of Interim Post-Approval Study Reports ................................................. 14 
 Evaluation of a Final PAS Report ................................................................................ 15 
  Sponsors Reporting Status ........................................................................................... 16 
  Study Status .................................................................................................................... 17 
  Failure to Complete a Post-Approval Study Requirement ........................................ 19 
  Public Disclosure of Post-Approval Study Information ............................................. 19 
 FDA Website .............................................................................................................. 19 
  Advisory Panels .......................................................................................................... 21 
 
 
     
  Contains Nonbinding Recommendations 
 
 
Procedures for Handling 
Post-Approval Studies Imposed by 
Premarket Approval Application 
Order 
 
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.  
 
  Introduction 
 
Evaluation of premarket approval applications (PMA) by the Food and Drug Administration 
(FDA) is a multi-step process in which we evaluate whether reasonable assurance of device 
safety and effectiveness has been demonstrated. To provide reasonable assurance, or the 
continued assurance, of safety and effectiveness of an approved device, we may require a post-
approval study (PAS) as a condition of approval in a PMA approval order under 21 CFR 
814.82(a)(2) and 21 CFR 814.82(a)(9).1 A PAS is usually a clinical or non-clinical study,2 as 
specified in the PMA approval order, and is typically intended to gather specific data to address 
questions about the postmarket performance of or experience with an approved medical device. 
As described in Balancing Premarket and Postmarket Data Collection for Devices Subject to 
Premarket Approval,3 FDA may consider it acceptable to collect certain data in the postmarket 
setting, rather than premarket under certain circumstances when FDA has uncertainty regarding 
certain benefits or risks of the device, but the degree of uncertainty is acceptable in the context of 
 
1 Under 21 CFR 814.82(a), FDA may impose post-approval requirements in a PMA approval order or by 
regulation at the time of approval of the PMA or by regulation subsequent to approval. The focus of this 
guidance document is on PAS imposed by a PMA approval order at the time of approval of the PMA. 
However, the recommendations in this guidance document may also apply to PAS imposed at the time of 
approval of humanitarian device exemption (HDE) applications.  
2 The focus of this guidance is on clinical studies; however, the concepts and principles discussed in this document 
may also apply to non-clinical PAS. 
3 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/balancing-premarket-and-postmarket-
data-collection-devices-subject-premarket-approval. 
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  Contains Nonbinding Recommendations 
 
 
the overall benefit-risk profile of the device at the time of premarket approval.4 
 
The purpose of this guidance document is to assist stakeholders with understanding PAS 
requirements imposed as a condition of PMA approval by providing: 
 
  procedural information;  
  recommendations concerning the format, content, and review of PAS-related 
submissions;  
  recommendations to help facilitate FDAs review of a PAS protocol in a timely manner;  
  recommendations for study timelines including enrollment milestones and study 
completion;  
  revised definitions to PAS status categories that we believe better reflect progress of the 
PAS; and 
  revised FDA review time goals for PAS-related submissions.  
 
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 use of 
the word should in Agency guidance means that something is suggested or recommended, but 
not required. 
 
  Background 
FDA established an internal tracking system for the PAS Program in 2006, and since that time, 
has implemented initiatives to increase transparency, including the establishment of the webpage 
for the Post-Approval Studies Program Database.5 The PAS Program Database typically displays 
the following information for each PAS: general information, general and detailed PAS protocol 
parameters, interim or final data summary, the sponsors progress or study status, and 
reporting information.  
 
Additionally, FDA may provide updates on the status of certain PAS requirements during public 
meetings of a Medical Device Advisory Committee Panel (an Advisory Panel) and, in the past, 
has invited sponsors to provide PAS updates to help ensure Advisory Panels are kept current on 
 
4 See the following FDA guidance documents for additional information on balancing premarket and postmarket 
data collection and benefit-risk determinations: Balancing Premarket and Postmarket Data Collection for Devices 
Subject to Premarket Approval (available at https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/balancing-premarket-and-postmarket-data-collection-devices-subject-premarket-approval); 
Breakthrough Devices Program (available at https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/breakthrough-devices-program); Consideration of Uncertainty in Making Benefit-Risk Determinations 
in Medical Device Premarket Approvals, De Novo Classifications, and Humanitarian Device Exemptions 
(available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/consideration-uncertainty-
making-benefit-risk-determinations-medical-device-premarket-approvals-de); and Factors to Consider When 
Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications: 
Guidance for Industry and Food and Drug Administration Staff (available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/factors-consider-when-making-benefit-risk-determinations-medical-
device-premarket-approval-and-de).  
5 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma_pas.cfm.  
5 
  Contains Nonbinding Recommendations 
 
 
the progress of a certain PAS. FDA may also provide PAS updates through other public 
communications. 
 
These PAS program initiatives aim to help ensure that: 
 
  sponsors conduct PAS that use valid scientific methodologies in the study design;  
  least burdensome6 approaches, including use of relevant and reliable real-world data 
(RWD),7 are followed when designing and conducting a PAS, as appropriate;  
  sponsors provide PAS results at intervals specified in the approval order; 
  FDA provides timely notification to sponsors regarding their PAS status; and 
  FDA posts PAS information publicly and, in situations where the legal criteria are met, 
undertakes regulatory actions such as withdrawal proceedings in accordance with section 
515(e) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360e(e)) 
and 21 CFR 814.46. 
 
  Post-Approval Study Requirements in PMA Approval 
Orders  
When a PAS is required as a condition of approval, the PMA approval order specifies certain 
information about the requirement (i.e., the reason or purpose for such requirement, the number 
of patients to be evaluated, and the reports required to be submitted).8 For each required PAS, 
FDA intends to describe the following in the PMA approval order: study design, objectives, 
population, and endpoints to be collected; the length of follow-up and frequency of assessments; 
and a high-level description of the data analysis plan for the primary endpoints. Generally, FDA 
also intends to specify PAS timelines in the approval order, including enrollment milestones (or 
data accrual milestones for a nonclinical study, if applicable), report submission timelines, 
completion timeline (e.g., complete follow-up and data analyses), and expectations for any 
additional milestones or submissions, as necessary.  
 
When a PAS is likely to be required as a condition of approval, sponsors and FDA should work 
collaboratively to establish a PAS protocol, enrollment milestones, and study completion 
timelines prior to PMA approval to help ensure that the PAS achieves its objectives and is 
completed in a timely manner. Based on FDAs experience with PAS and the importance of 
timely postmarket data collection for ensuring continued device safety and effectiveness, the 
enrollment milestones below are recommended in developing your study protocol for clinical 
studies.   
 
 
6 See FDA Guidance Least Burdensome Provisions: Concept and Principles, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/least-burdensome-provisions-concept-
and-principles. 
7 See FDA Guidance, Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices, 
available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-real-world-
evidencesupport-regulatory-decision-making-medical-devices. 
8 See 21 CFR 814.82(a)(2).  
 
6 
  Contains Nonbinding Recommendations 
 
 
  First subject enrolled within 6 months of the study protocol approval date9 
  20% of subjects enrolled within 12 months of the study protocol approval date 
  50% of subjects enrolled within 18 months of the study protocol approval date 
  100% of subjects enrolled within 24 months of the study protocol approval date 
 
These recommended milestones are intended to be reflective of those that are most likely to 
result in successful PAS completion in a timely manner. FDA expects for manufactures to meet 
PAS requirements outlined in the PMA approval order and FDA intends to use the milestones 
identified in the approval order to assess study status.  
 
For non-clinical studies, similar milestones for data accrual can also be used to track study 
progress. 
 
  Post-Approval Study Protocols 
In general, when a PAS is required as a condition of approval of the PMA, prior approval of the 
PAS protocol10 is included as part of the condition. Sponsors should engage with FDA as early 
as possible in the PMA review to discuss the need for and details of a PAS protocol. FDA 
intends to review the PAS protocol interactively with the sponsor during the review of the PMA. 
Section IV.B. and Section IV.C. describe the process for submission and review of PAS 
protocols and changes after PMA approval. 
 
 Recommended Elements in a Post-Approval Study Protocol  
FDA recommends you include the following elements in a PAS protocol: 
 
  background (e.g., devices regulatory history, brief description of device, indications for 
use) 
  purpose of study 
  study objectives 
  study design  
  study population (including subject inclusion and exclusion criteria and definition, 
source of comparator group, and targets for ensuring diversity with respect to sex,11 age, 
race, and ethnicity12, as appropriate) 
  enrollment and recruitment plan  
  sample size calculation that is statistically justified and based on study hypothesis, where 
 
9 The date of the PAS protocol approval is the date the PMA or PMA supplement, which includes the full PAS 
protocol, is approved. 
10 Use of the term protocol(s) throughout this guidance is intended to reflect the complete study plan which 
includes PAS protocol, data collection forms, informed consent forms, IRB documentation, and enrollment 
milestones/study timelines. 
11 See FDA guidance, Evaluation of Sex-Specific Data in Medical Device Clinical Studies (available at 
https://www.fda.gov/media/82005/download). 
12 See FDA guidance, Evaluation and Reporting of Age-, Race-, and Ethnicity-Specific Data in Medical Device 
Clinical Studies (available at https://www.fda.gov/media/98686/download). 
7 
  Contains Nonbinding Recommendations 
 
 
applicable 
  primary and secondary endpoints, when applicable, including definitions for study 
endpoints and list of adverse events/complications 
  procedures for a determination of adverse events/complications relatedness with device 
and/or the procedure 
  length of follow-up, follow-up schedule, plans to minimize losses to follow-up,13 and 
estimated follow-up rates 
  description of baseline and follow-up assessments 
  description of data collection procedures (including data management and quality 
control) 
  data analyses and statistical tests planned (such as a statistical analysis plan) 
  interim data release plan (include frequency of interim analyses, type of analysis, data 
endpoints that will be assessed, content (i.e., endpoints to be posted) and proposed 
frequency of posting on the FDAs PAS Program Database webpage), when appropriate  
  data collection forms 
  informed consent forms 
  Institutional Review Board (IRB) approval documentation 
  enrollment milestones and study timelines (see Section III) 
 
 Post-Approval Study Protocol Review  
When a PAS is likely to be required as a condition of approval of the PMA, FDA intends to 
review the PAS protocol interactively with the sponsor during the review of the PMA and 
concurrent with the review of the premarket data. FDAs goal is to complete the review of the 
PAS protocol and establish study enrollment milestones and completion timelines at the time of 
PMA approval, for inclusion as part of the conditions of approval within the PMA approval 
order. Accordingly, we recommend that the PMA include a discussion of potential postmarket 
evaluation needs, a proposed PAS protocol or PAS outline (including objective and general study 
design, study population, study endpoints, sample size, length of follow-up, frequency of 
assessments, and enrollment milestones), or the sponsors rationale as to why a PAS is not 
needed.  
 
If a PAS protocol has not been developed by the time of PMA approval, the PMA may be 
approved with a PAS outline. In these circumstances, FDA intends to require, as part of the 
condition of approval in the PMA approval order, that a PAS protocol must be submitted as a 
 
13 See FDA guidance Patient Engagement in the Design and Conduct of Medical Device Clinical Investigations: 
Guidance for Industry, Food and Drug Administration Staff, and Other Stakeholders (available at: 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-engagement-design-and-
conduct-medical-device-clinical-investigations) as a potential approach to minimize losses to follow-up.  
8 
  Contains Nonbinding Recommendations 
 
 
PMA supplement14 within 30 calendar days15 of the PMA approval date.16 Your PMA 
supplement should be clearly labeled as a PAS Protocol. If there are multiple PAS protocols 
being finalized after PMA approval, we recommend each protocol be submitted as a separate 
PMA supplement. FDA strives to finish its review of a study protocol within 60 calendar days of 
PMA approval17. To achieve this, FDA intends to complete the review of a PAS protocol (a 
PMA supplement) and respond within 30 calendar days of receipt. Sponsors should prioritize 
resolution of any protocol deficiencies and work interactively with FDA to help ensure that 
FDAs review of the protocol is completed within 60 calendar days from the PMA approval date.  
 
 How to Submit Changes to an Approved Post-Approval 
Study Protocol 
If you wish to propose a change to an approved PAS protocol (e.g., changes to sample size, 
endpoints, follow-up assessments) or to data collection forms, informed consent forms, and IRB 
documentation after PMA approval, you should submit a PMA supplement, clearly labeled as a 
PAS Protocol, for FDA review and approval. If multiple PAS protocols are revised, we 
recommend each be submitted as a separate PMA supplement.  
 
FDA understands that study delays sometimes may occur, however, FDA generally does not 
intend for sponsors to routinely modify the PAS protocols in order to adjust study milestones.  
Sponsors may request changes to the original enrollment milestones identified in the PMA 
approval order and FDA intends to consider these on a case-by-case basis.18 An example of 
where a change to the original study milestone could be appropriate might be when new 
information indicates that the original study enrollment milestones were impractical at the time 
of the PMA approval order. Based on past experience, FDA expects that it may be appropriate in 
limited circumstances to revise the original study milestones in the PMA approval order and 
intends to determine the study progress and to designate its status (e.g., as pending, ongoing, or 
delayed) based on the milestones specified in the PMA approval order. See Section V and 
Section VI.C. for recommendations regarding the communication of anticipated or occurring 
study delays in progress reports. See Section VII for considerations for mitigating study delays. 
   
 What Happens if the Sponsor and FDA Cannot Complete 
the Development of a Post-Approval Study Protocol 
FDA intends to facilitate timely discussions with sponsors concerning PAS protocol issues and 
 
14 PMA supplements containing only a PAS protocol should be submitted as supplements with no user-fee. See 
FDAs guidance 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) 
15 Use of the term calendar days throughout this guidance is intended to distinguish calendar days from working 
days. 
16 See 21 CFR 814.82(a).  
17 FDA intends to review study protocols within 60 calendar days of PMA approval but actual review times may be 
longer in certain cases, such as when there is a government shutdown or other disruptions to normal operations. 
18 Proposed changes to study enrollment milestones should be submitted as a PMA supplement. Such requests 
should not be combined with any other requests for changes to the PAS protocol. 
9 
  Contains Nonbinding Recommendations 
 
 
challenges. We believe that early and ongoing interactions should be the primary method to 
discuss PAS protocols and resolve any PAS issues. However, if FDA is unable to complete its 
review of the study protocol within 60 calendar days after PMA approval due to outstanding 
deficiencies that the sponsor needs to address, we intend for the PAS status to be categorized as 
Protocol Overdue on FDAs PAS Program Database webpage19 (see Section X for more 
information on study status).  
 
  When and How to Submit Post-Approval Study Reports 
FDA may impose post-approval requirements in a PMA approval order or by regulation at the 
time of approval of the PMA or by regulation subsequent to approval. Such requirements may 
include continuing evaluation and periodic reporting on the safety, effectiveness, and reliability 
of the device for its intended use.20 FDA tracks and evaluates the conduct of a PAS through 
review of study reports submitted to the Agency. An interim report is a written report to FDA on 
the status of the PAS prior to its completion. Generally, FDA recommends submitting two types of 
interim reports: Enrollment Status Report and PAS Progress Report. An Enrollment Status 
Report should provide the progress towards meeting the enrollment milestones per the approval 
order (see Section III). A PAS Progress Report should describe the status of the PAS prior to its 
completion, including subject accountability, as well as device performance, and safety and 
effectiveness data (see Section VI for additional report content details). When delays are 
anticipated or are occurring, sponsors should notify FDA in the next scheduled PAS Progress 
Report of the delays, reasons, and plans to address challenges and meet established milestones 
identified in the PMA approval order. A Final PAS Report is a written report of a completed or 
terminated PAS.  
   
FDA intends for the PMA approval order to include a submission timeline for PAS reports. The 
timing of Enrollment Status Reports may be based on the deadlines identified for each 
enrollment milestone. There may be instances in which the timing for the submission of an 
Enrollment Status Report coincides with the timing for the submission of a PAS Progress Report. 
In such instances, a sponsor may decide to submit one report labeled as Enrollment Status and 
PAS Progress Report to address reporting requirements.21 If study enrollment milestones are 
missed, FDA may change the timing of your Enrollment Status Reports. Generally, FDA intends 
to require in the approval order that PAS Progress Reports are to be submitted every six (6) 
months until subject enrollment has been completed and annually thereafter; PAS Progress 
Reports for PAS without new subject enrollment (e.g., extended follow-up of premarket cohorts) 
are to be submitted every six (6) months for the first year of the study and annually, thereafter, 
from the date of the PMA approval letter or other negotiated starting date, unless a different 
reporting schedule is agreed upon. You must follow the reporting schedule, as required by the 
PMA approval order, until you have submitted the Final PAS Report. Generally, FDA intends to 
require in the approval order that the Final PAS Report is to be submitted no later than three 
months after study completion (i.e., last subjects last follow-up date), unless a different 
 
19 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma_pas.cfm. 
20  See 21 CFR 814.82(a)(2) 
21 FDA recommends the sponsor contact FDA if they wish to combine reports or submit one report for more than 
one PAS. 
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  Contains Nonbinding Recommendations 
 
 
reporting schedule post study completion is agreed upon.  
 
To help facilitate and triage review, FDA recommends that the sponsor indicate the type of PAS 
report and time span on the report cover letter in bold letters (e.g., Enrollment Status Report, 6-
Month PAS Progress Report, 12-Month PAS Progress Report, Final PAS Report). We also 
recommend that the sponsor identify the condition of approval for which the report is being 
submitted (i.e., refer to the condition of approval wording and the PAS number if more than one 
PAS is identified as a condition of approval in the approval order).  
 
FDA requires all applicants to provide one electronic copy (eCopy) of PAS submissions.22 The 
eCopy must be accompanied by a single paper copy of your signed cover letter. Submissions 
should be sent to the current address displayed on the website 
http://www.fda.gov/cdrhsubmissionaddress. 
 
  Content and Format of Interim and Final Post-
Approval Study Reports 
FDAs ability to adequately track and evaluate a PAS depends on the quality and timeliness of 
the information provided by the sponsor. The recommendations in this section are intended to 
help ensure the PAS reports that are submitted contain adequate information for FDA to identify 
the product being studied, the specific study being conducted, the status of that study, and, if 
applicable, the reasons for any delays or failures to complete the study in accordance with the 
timelines typically included in the approval order.  
 
FDA recommends that PAS reports (interim and final) include the information listed below, 
clearly identified, and in separate sections. All reports should contain the data listed below and 
submitted per the timeline in the approval order. For some studies (e.g., retrospective analysis of 
RWD,23 non-clinical studies), sponsors are encouraged to work with FDA to determine the 
applicability of the PAS Enrollment Status Report and content of any PAS reports.  
 
 General Information 
FDA recommends all reports include a section that contains the following general information: 
 
  PMA application number and, if applicable, the supplement number for which the PAS 
requirement was made a condition of approval in the PMA approval order 
  Sponsor name and contact information (name of the individual or entity holding the 
approved PMA): 
  Company Name/Institution Name 
o
 
22 See Section 745A(b) of the FD&C Act and FDAs eCopy guidance, eCopy Program for Medical Device 
Submissions, available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ecopy-
program-medical-device-submissions.  
23 See FDA guidance, Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices, 
available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-real-world-evidence-
support-regulatory-decision-making-medical-devices. 
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  Contains Nonbinding Recommendations 
 
 
  Street Address 
o
  City 
o
  State/Province 
o
  ZIP/Postal Code 
o
  Phone Number (include area code) 
o
  Contact name and title 
o
  Contact e-mail address 
o
  Report correspondent/contact information (if different from sponsor):24 
  Company Name/Institution Name 
o
  Street Address 
o
  City 
o
  State/Province 
o
  ZIP/Postal Code 
o
  Phone Number (include area code) 
o
  Contact name and title 
o
  Contact e-mail address 
o
  Date of the original PMA or, if applicable, of the PMA supplement approval  
  Date of PAS protocol approval and, if applicable, date(s) of approval of protocol 
revision(s) 
  Device trade name(s) 
  Device model number(s) 
  Date of report submission 
  Description of the data included in the report, including: 
  Enrollment data 
o
  Clinical study data 
o
  Non-clinical data (e.g., bench/laboratory)  
o
  Animal study data25 
o
  Other (specify) 
o
  Type of submission:  
  Enrollment Status Report 
o
  PAS Progress Report 
o
  Final PAS Report 
o
  Response to FDA report deficiency letter  
o
  Other (specify) 
o
 
 PAS Enrollment Status Reports 
FDA intends to specify the schedule for Enrollment Status Reports within the PMA approval 
order. Generally, sponsors should submit Enrollment Status Reports until enrollment is 
 
24 If the correspondent/contact information changes for a PAS submission, contact 
MandatedStudiesPrograms@fda.hhs.gov. 
25 FDA supports the principles of the 3Rs, to reduce, refine, and replace animal use in testing when feasible. We 
encourage sponsors to consult with us if they wish to use a non-animal testing method they believe is suitable, 
adequate, validated, and feasible. We will consider if such an alternative method could be assessed for equivalency 
to an animal test method.  
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  Contains Nonbinding Recommendations 
 
 
completed.26 The sponsors Enrollment Status Reports should include sufficient data for FDA to 
track progress towards the study enrollment milestones as specified in the PMA approval order, 
including (as applicable): 
 
  Begin and end dates of period covered by the report  
  Start and completion dates for clinical site(s) recruitment 
  Number of IRB approvals and number of clinical sites at which the study was initiated 
  Subject-enrollment start date and expected completion date 
  Number of subjects enrolled (if applicable, this data should be presented for the entire 
subject population and for each subgroup, including sex,27 age, race, and ethnicity28, as 
appropriate) 
  Comparison of target versus actual enrollment dates based on enrollment milestones 
specified in the PMA approval order 
   
 PAS Progress Reports 
FDA recommends PAS Progress Reports include (as applicable): 
 
  Purpose of the study, including study goals, objectives, and primary and secondary study 
endpoints 
  Description of the study population, including: 
  specific illness or condition 
o
  whether the study targets subpopulations (e.g., pediatric, geriatric), and targets for 
o
ensuring diversity with respect to sex,29 age, race, and ethnicity30, as appropriate 
  total number of subjects to be enrolled 
o
  schedule of subject follow-up 
o
  Begin and end dates of period covered by the report 
  Date the sponsor used as cut-off for database for the analysis included in the report 
(should not exceed three months prior to the submission of report) 
  Subject accountability (e.g., enrolled, randomized, completed, withdrawn, lost to follow-
up) at each follow-up timepoint, for the entire population and broken down by 
subgroups, if applicable. To limit the potential bias in safety and effectiveness data, the 
sponsor should make every effort to reduce the number of subjects lost to follow-up. 
  An explanation for: 
  delays in enrollment and plans to address challenges and meet established 
o
milestones specified in the PMA approval order  
  subjects lost to follow-up, if known, as well as any measure to minimize such future 
o
 
26 For non-clinical PAS data, accrual milestone reports may be used to track progress. 
27 See FDA guidance, Evaluation of Sex-Specific Data in Medical Device Clinical Studies (available at 
https://www.fda.gov/media/82005/download). 
28 See FDA guidance, Evaluation and Reporting of Age-, Race-, and Ethnicity-Specific Data in Medical Device 
Clinical Studies (available at https://www.fda.gov/media/98686/download). 
29 See FDA guidance, Evaluation of Sex-Specific Data in Medical Device Clinical Studies (available at 
https://www.fda.gov/media/82005/download). 
30 See FDA guidance, Evaluation and Reporting of Age-, Race-, and Ethnicity-Specific Data in Medical Device 
Clinical Studies (available at https://www.fda.gov/media/98686/download). 
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events 
  subject and healthcare provider-initiated discontinuations 
o
  any deaths, including reports from post-mortem examinations 
o
  Summary of safety and/or effectiveness data and an interpretation of study results to date 
  Proposed interim summary data to be posted on FDAs PAS Program Database webpage 
31  
 
 Final Post-Approval Study Status Reports 
FDA recommends a Final PAS Report include (as applicable): 
 
  Purpose of the study, including goals, objectives, and primary and secondary endpoints 
  Description of the study population, including: 
  specific illness or condition 
o
  whether the PAS targets subpopulations (e.g., pediatric, geriatric), and targets for 
o
ensuring diversity with respect to sex,32 age, race, and ethnicity33, as appropriate 
  total number of subjects to be studied 
o
  schedule of subject follow-up 
o
  Begin and end dates of period covered by the Final PAS Report 
  Date of database closure for the Final PAS Report  
  Final accountability of enrolled subjects compared to target  
  Final accountability of number of subjects (e.g., enrolled, randomized, completed, 
withdrawn, lost to follow-up) at each study follow-up timepoint, for the entire 
population and broken down by subgroups, if applicable 
  An explanation for: 
  subjects lost to follow-up, if known  
o
  subject and healthcare provider-initiated discontinuations 
o
  any deaths, including reports from post-mortem examinations 
o
  assessment of potential bias introduced by losses to follow-up (e.g., are subjects lost 
o
to follow-up different from those that remained in the study? Is the loss to follow-
up differential by study group?) and potential impact on interpretation of results  
  Summary and interpretation of final safety/effectiveness findings 
  Proposed summary data to be posted on FDAs Post-Approval Studies (PAS) Database 
webpage34 
 
  Evaluation of Interim Post-Approval Study Reports 
 
Enrollment Status Report: FDA intends to review Enrollment Status Reports to assess progress 
 
31 FDA will make the final determination of what information is posted on the PAS Program Database webpage 
based on the totality of our review and consistent with applicable disclosure laws. 
32 See FDA guidance, Evaluation of Sex-Specific Data in Medical Device Clinical Studies (available at 
https://www.fda.gov/media/82005/download). 
33 See FDA guidance, Evaluation and Reporting of Age-, Race-, and Ethnicity-Specific Data in Medical Device 
Clinical Studies (available at https://www.fda.gov/media/98686/download). 
34 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma_pas.cfm  
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towards the study enrollment milestones identified in the PMA approval order (i.e., comparing 
study enrollment milestones to actual enrollment).  
 
PAS Progress Report: FDA intends to consider several factors when evaluating the PAS 
Progress Report, including: 
 
  the completeness of the report content (especially in regard to progress towards 
achieving primary and secondary endpoints and performance goals, or sufficient 
individual endpoint data to infer progress in the case of composite endpoints); 
  protocol adherence and reasons for deviations from the methodology;  
  the performance and postmarket safety and effectiveness of the device; 
  whether study enrollment milestones are met (see Section X); 
  causes for delays in PAS progress or failure to meet enrollment milestones and plan to 
address challenges and meet established milestones; 
  When a sponsor fails to meet enrollment milestone requirements, FDA expects 
o
sponsors to act with due diligence to mitigate continued study delays. FDA intends 
to consider the sponsors mitigation efforts to address study delays. Mitigation 
efforts may include, but are not limited to, the following: 
-  current and past enrollment recovery efforts; 
-  evaluation of slow enrollment; 
-  device availability on the market; 
-  measures taken to initiate study sites; 
-  measures taken to incentivize study subjects; 
-  outreach to study investigators and potential subjects; and  
-  plans to remove barriers to site and subject participation. 
Although it is recommended that the sponsor identify any missed milestones as part of PAS 
reports, the sponsor should communicate circumstances which are impacting their ability to meet 
PAS requirements to FDA as soon as possible. 
 
FDA intends to review interim PAS reports within 30 calendar days of submission receipt date. 
If we have questions regarding the data provided in the report, or if we believe the data are 
incomplete or insufficient, we may request additional information interactively and/or through a 
deficiency letter. If an interim report includes insufficient data or the sponsor failed to meet 
enrollment milestones or study timelines, FDA ultimately may take enforcement actions to 
ensure compliance with PAS requirements, as appropriate (see Section XI). Additionally, if the 
PAS results identify new safety and/or effectiveness concerns for a device, FDA may consider 
taking actions, which may include issuing a Safety Communication to provide recommendations 
on patient management, as appropriate.  
 
   Evaluation of a Final PAS Report 
The Final PAS Report should describe the study methodology and results. If the Final PAS 
Report is for a completed study, it should also explain how the study fulfills the PAS 
requirement identified in the PMA approval order. If the Final PAS Report is for a terminated 
study, it should include the data captured prior to termination. See Section VI for additional 
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recommendations on the content and format of PAS reports. 
 
FDA intends to consider multiple factors when evaluating a Final PAS Report, including: 
 
  the completeness of the report content; 
  adherence to methodology in the PAS protocol and reasons for deviations from the 
methodology; 
  evaluation of data in the report to assess the performance, safety and effectiveness of the 
device; and 
  evaluation of fulfillment of the condition(s) of approval identified in the PMA approval 
order. 
 
FDA intends to review final PAS reports within 60 calendar days of submission receipt date. If 
we have questions regarding the data provided in the Final PAS Report, or if we believe the data 
are incomplete or insufficient to address the PAS requirement(s), we intend to request additional 
information interactively and/or through a deficiency letter. Additionally, if the PAS results 
identify new safety and/or effectiveness concerns for a device, FDA may consider taking action, 
which may include issuing a Safety Communication, as appropriate. 
 
If we conclude the sponsor has fulfilled the PAS requirement(s), we intend to send the sponsor a 
letter stating the PAS requirement(s) has been fulfilled. Generally, submission of additional PAS 
reports to FDA is not necessary after FDA determines that the PAS requirement is satisfied. If 
the PAS results affect device labeling, the labeling change will generally trigger the need to 
submit a PMA supplement (21 CFR 814.39).35  
 
   Sponsors Reporting Status 
Upon receipt of a PAS Progress Report or a Final PAS Report, FDA intends to assess the 
sponsors reporting status based on the schedule specified in the PMA approval order and post 
the reporting status on the webpage for the PAS Program Database36 for each PAS Progress and 
Final Report submission. The reporting status categories are described in Table 1 below. 
 
 
 
 
 
 
   
 
35 PMA supplements that include only labeling changes reflecting the results from a PAS should be submitted as 
supplements with no user-fee. See FDAs guidance 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) 
36 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma_pas.cfm 
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Table 1. Reporting Status Categories 
 
Status    Definition 
Report on Time  FDA has received the PAS Progress Report or Final PAS Report per 
the PMA approval order. 
Report Overdue  FDA has not received the PAS Progress Report or Final PAS 
Report per the PMA approval order. 
Report  FDA has received the PAS Progress Report or Final PAS Report, 
Overdue/Received  although receipt was after the due date set in the PMA approval 
order. 
 
  Study Status 
FDA intends to determine the PAS status after reviewing a PMA supplement (i.e., a protocol for 
a new PAS or modifications to a PAS protocol), an Enrollment Status Report, a PAS Progress 
Report, and a Final PAS Report. Factors in considering the PAS progress and status include, as 
applicable: 
 
1.  Assessing the status of protocol approval;  
2.  After PAS protocol approval, assessing the following:  
a.  Whether the study enrollment milestones are met  
b.  Progress with data accrual  
c.  Submission of a Final PAS Report  
 
Based on the above, FDA intends to consider the appropriate status category to be posted on the 
webpage for the PAS Program Database.37  Of note, there may be circumstances in which a PAS 
may be put on a hold temporarily, be redesigned/replaced, or be terminated. A sponsors 
progress status is considered based on currently available information and may be revised 
accordingly based on the availability of new information. FDA generally intends to use the 
original study schedule identified in the PMA approval order to assess the study progress and to 
designate its status (see Section IV.C.). Each of these status categories are described in Table 2 
below.  
 
Table 2. PAS Status Category 
 
Status  Definition 
Protocol Pending  This category is used when a protocol was not approved at the time of 
the PMA approval order and it has been less than 60 calendar days 
since issuance of the PMA approval order.  
Protocol Overdue  FDA is unable to complete its review of the study protocol due to 
outstanding deficiencies that the sponsor needs to address and it has 
been more than 60 calendar days since issuance of the PMA approval 
order. 
 
37 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma_pas.cfm. 
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Study Pending  This category is used from the time the PAS protocol has been 
approved to the initial status assessment based on the data in the first 
Interim PAS report. 
Ongoing  The study is proceeding according to, or is ahead of, the study 
timelines specified in the PMA approval order. The FDA considers the 
study to be ongoing until a Final PAS Report is submitted to the FDA, 
as long as the activities are proceeding according to the approved PAS 
protocol. 
Delayed  The progression of the study is behind the study timelines specified in 
the PMA approval order. For example, the enrollment of subjects (or 
data accrual) may or may not have started but the projected date for 
completion of that milestone has passed. Delays can occur in any 
phase of the study, including subject enrollment, analysis of data, or 
submission of the Final PAS Report to the FDA. While the enrollment 
milestones specified in the PMA approval order serve as the basis for 
defining the study as delayed, each phase of the study will be 
considered on its own right. If the sponsor has one delayed phase, but 
gets back on schedule during the next phase, the delayed status will no 
longer apply. 
 
Completed  The sponsor has fulfilled the post-approval requirement identified in 
the condition(s) of approval (PAS requirement) in the PMA approval 
order, and FDA considers the PAS requirement to be satisfied.  
 Redesigned/Replaced  The sponsor has not fulfilled or cannot fulfill the post-approval 
requirement identified in the condition(s) of approval (PAS 
requirement) as originally designed. All reasonable efforts to fulfill the 
PAS requirement have been exhausted, and FDA has agreed to allow 
the sponsor to redesign and replace the original PAS protocol with a 
new PAS protocol to fulfill the post-approval requirement. The new 
PAS protocol supersedes the previous protocol.  
Terminated  The sponsor has not fulfilled or cannot fulfill the post-approval 
requirement identified in the condition(s) of approval (PAS 
requirement), e.g., postmarket questions are no longer relevant, device 
is not currently being sold and sponsor withdraws premarket 
submission that received the PAS as condition of approval. If FDA 
determines that all appropriate efforts to fulfill the condition of 
approval have been exhausted, FDA intends to terminate the study.  
Hold   This status reflects when a study has been placed on a hold 
temporarily. Examples of situations when a PAS might be temporarily 
paused include the following examples:  
  while a change in ownership is completed, a pending separate 
study is being used to address condition of approval, or 
  ceased device sales, but the premarket submission associated 
with the PAS is not withdrawn.  
When the circumstances necessitating the hold have resolved, the 
sponsor is responsible for resuming the PAS. The progress is assessed 
against approved study milestones.  
 
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  Failure to Complete a Post-Approval Study 
Requirement 
There may be circumstances that make it impossible or inappropriate for the sponsor to complete 
a PAS requirement. For instance, the sponsor may have instituted a voluntary withdrawal or 
recall of the device from the market that impacts the sponsors ability to complete the PAS.   
 
In addition, if FDA believes the PAS cannot be completed as designed or can no longer address 
the study questions, FDA intends to discuss with the sponsor the need to redesign the PAS and, 
establish a new PAS protocol and timelines to fulfill the PAS requirement. We recommend that 
the sponsor initiate early communication with FDA if they encounter barriers that limit the 
ability to fulfill their PAS requirement. 
 
If FDA concludes the sponsor has not complied with a PAS requirement and the sponsor has not 
provided a valid justification for doing so, we may take a variety of actions. Under certain 
circumstances, we may initiate withdrawal of approval of the PMA under section 515(e) of the 
FD&C Act. In appropriate instances, FDA may order postmarket surveillance under section 522 
of the FD&C Act. Note that the failure or refusal to comply with section 522 is a prohibited act 
under section 301(q)(1)(C) of the FD&C Act, 21 U.S.C. 331(q)(1)(C). Further, under section 
502(t)(3) of the FD&C Act, 21 U.S.C. 352(t)(3), a device is misbranded if there is a failure or 
refusal to comply with any requirement under section 522 of the FD&C Act. Please note that 
violations of sections 301(q)(1)(C) or misbranding under section 502(t)(3) may lead to 
enforcement actions including seizure, injunction, prosecution, or civil money penalties. 
 
   Public Disclosure of Post-Approval Study Information 
 FDA Website 
To increase transparency to FDA stakeholders, including consumers, patients, healthcare 
providers, and industry, FDA posts certain information about PAS (e.g., study description and 
interim or final study results, see details below) on the webpage for the PAS Program 
Database.38 This information will be posted in compliance with the requirements of 21 CFR 
814.9 on the confidentiality of data and information in the PMA file and 21 CFR Part 20 on the 
public disclosure of information.  
 
PAS-related information that may be posted includes: 
 
General Information 
  PMA number 
  sponsor name 
  device name 
  medical specialty (e.g., cardiovascular, orthopedic) 
  date of issuance of PMA approval order 
 
38 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/PMA_pas.cfm. 
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  PAS name 
  PAS protocol approval date 
  PAS status  
 
General PAS Parameters 
  study design  
  data source(s) 
  comparison group, if applicable 
  analysis type (i.e., descriptive, analytic)  
  study population 
 
Detailed PAS Parameters 
  detailed description of the study design 
  study milestones (in the PMA approval order) 
  required sample size (number of subjects and sites) 
  description of study population 
  description of study endpoint(s) 
  follow-up visits and length of follow-up (when applicable)  
 
Interim PAS Report Data 
 
FDA intends to post on its website, or otherwise make public, PAS interim results consistent 
with the interim data release plan (included as part of the PAS protocol) and may post additional 
information that may be beneficial for public awareness. If the PAS protocol does not include an 
interim data release plan, FDA intends to post PAS interim summary data and/or FDA analyses 
thereof when appropriate to protect the public health, such as in cases where interim results raise 
safety concerns, serve to provide critical device performance information, or may otherwise 
impact treatment. FDA generally considers such data to be publicly releasable in accordance 
with applicable disclosure laws, such as the Freedom of Information Act. When sharing 
information appropriate to protect public health, FDA will consider the benefits of sharing the 
information, as well as other considerations on the study conduct. Examples of interim report 
data that FDA may publicly disclose includes: 
 
  number of subjects enrolled 
  number of sites enrolled 
  interim safety/effectiveness findings. 
 
However, if a sponsor believes in a particular instance that interim results are restricted from 
public release; for example, because they constitute personal identifying information, trade 
secrets, or confidential commercial information, they should notify FDA of this in the interim 
report containing the results and explain why they believe disclosure of the data is restricted. 
 
Final PAS Report Results (where applicable) 
 
FDA intends to post on its website or otherwise make public PAS final summary data and/or 
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FDA analyses when studies are completed. FDA generally considers such data to be publicly 
releasable in accordance with applicable disclosure laws, such as the Freedom of Information 
Act. Final PAS data that is posted may include: 
  
  final number of study subjects enrolled 
  final number of study sites enrolled 
  subject follow-up rate 
  final safety/effectiveness findings and results 
  FDAs interpretation and summation of the study strengths/weaknesses and if a labeling 
update is recommended. 
 
Reporting Information 
 
  PAS Progress Report and Final PAS Report schedule 
  due date(s) for interim and final reports (based on schedule in the PMA approval order) 
  FDA receipt date(s) of PAS Progress Report and Final PAS Report 
  receipt status category for PAS Progress Report and Final PAS Report 
 
 Advisory Panels 
FDA may seek the advice of an Advisory Panel when considering the initiation or progress of a 
PAS, or for input on data that raise concerns regarding the safety and/or effectiveness of a 
device. These Advisory Panels are composed of experts outside FDA who independently review 
information and make recommendations to FDA.39 Although not always part of an Advisory 
Panel meeting, in order to, for example, help ensure the Advisory Panel is kept current on the 
progress of a certain PAS, FDA may present or request that the sponsor present the status or 
outcomes of a PAS during a scheduled public meeting. When asked to present at such meetings, 
we recommend that the sponsors presentation contains the report contents described in Section 
VI. FDAs presentations at such meetings are anticipated to include our analysis and evaluation 
of the PAS. 
 
39 See FDA Guidance Preparation and Public Availability of Information Given to Advisory Committee Members, 
issued August 1, 2008, available at https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/preparation-and-public-availability-information-given-advisory-committee-members. See also FDA 
Guidance Procedures for Meetings of the Medical Devices Advisory Committee, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/procedures-meetings-medical-devices-
advisory-committee. See also the Medical Devices Advisory Committee Charter, available at 
https://www.fda.gov/advisory-committees/medical-devices-advisory-committee/charter-medical-devices-advisory-
committee.  
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