Contains Nonbinding Recommendations
Enforcement Policy for Certain 
Supplements for Approved Premarket 
Approval (PMA) or Humanitarian 
Device Exemption (HDE) Submissions 
Guidance for Industry and
Food and Drug Administration Staff
Document issued on November 2, 2023.
This document supersedes 
Supplements for Approved Premarket Approval (PMA) or Humanitarian 
Device Exemption (HDE) Submissions During the Coronavirus Disease 2019 
(COVID-19) Public Health Emergency, issued in May 2020 and updated in 
May 2022, and March 2023.
For questions about this document, contact the Office of Regulatory Policy/Division of 
Submission Support at 301-796-5640 or CDRHPremarketProgramOperations@fda.hhs.gov, or 
the Office of Communication, Outreach and Development (OCOD) at 240-402-8010, or 
ocod@fda.hhs.gov.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Devices and Radiological Health (CDRH)
Center for Biologics Evaluation and Research (CBER) 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-2023-D-4595. 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 email request to CDRH-
Guidance@fda.hhs.gov or ocod@fda.hhs.gov to receive a copy of the guidance. Please include 
the document number GUI00020028 and complete title of the guidance in the request. Contains Nonbinding Recommendations
Enforcement Policy for Certain 
Supplements for Approved Premarket 
Approval (PMA) or Humanitarian 
Device Exemption (HDE) Submissions 
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  
TheFood and Drug Administration (FDA or the Agency) plays a critical role in protecting the 
United States from threats such as emerging infectious diseases, including the Coronavirus 
Disease 2019 (COVID-19) pandemic and other public health emergencies (PHEs).  
 
Following approval of a PMA or HDE, an applicant generally must submit a PMA or HDE 
supplement for review and approval by FDA before making changes affecting the safety and 
effectiveness of the device unless FDA has advised that an alternative type of submission is 
permitted for a particular change (e.g., 30-day notice).1 Following the emergence of COVID-19, 
FDA first issued this guidance in May 2020 announcing a policy concerning manufacturing 
processes adjustments to accommodate manufacturing personnel safety relating to the emergency 
(i.e., social distancing), adaption of manufacturing or design modifications due to supply chain 
disruptions, and/or moving device production as a result of COVID-19 impacts. In May 2022, 
FDA updated this guidance to clarify the examples of circumstances, including changes made to 
microchips or other associated circuitry and/or software changes, where FDA believed a 
modification would generally not create an undue risk in light of the public health emergency 
and may be needed to address manufacturing limitations or supply chain issues. At the time, 
FDA stated that the policy described in this guidance was intended to remain in effect only for 
1See section 515(d)(5)(A) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 CFR 814.39, and 21 CFR 
814.108.
1 Contains Nonbinding Recommendations
the duration of the public health emergency related to COVID-19 declared by the Secretary of 
Health and Human Services (HHS) in accordance with section 319 of the Public Health Service 
Act (PHS Act). On March 13, 2023, FDA announced in the Federal Register notice Guidance 
Documents Related to Coronavirus Disease 2019 (COVID-19),2 that this guidance document 
was being revised to continue in effect for 180 days after the COVID-19 PHE declaration 
expires, and that, during that time, FDA intends to further revise the guidance.
The policy set forth in this guidance was initially intended to address certain manufacturing 
adjustments and adaptations that needed to be made expeditiously to avoid supply chain 
disruptions and device shortages or to ensure manufacturing personnel safety during the COVID-
19 PHE. Since first issuing the Supplements for Approved Premarket Approval (PMA) or 
Humanitarian Device Exemption (HDE) Submissions During the Coronavirus Disease 2019 
(COVID-19) Public Health Emergency guidance in May 2020, FDAs experience has generally 
demonstrated that the public health equities weigh in favor of exercising certain enforcement 
policies for submission of certain PMA and HDE supplements beyond a 180-day extension after 
the expiration of the COVID-19 PHE (which expired on May 11, 2023). More specifically, FDA 
has evaluated the benefits and risks to patients and healthcare providers of exercising certain 
enforcement policies including identifying certain device modifications for which enforcement 
policies might be appropriate, and assessing other lessons learned from implementation of 
COVID-19-related enforcement policies for certain device modifications. In addition, 
notwithstanding the expiration of the public health emergency, FDA has continued to observe 
supply chain challenges and shortages of medical devices remain widespread. Although this 
guidance has been revised to remove any expiration date for the enforcement policy, FDA 
intends to continue to monitor the situation and may make further revisions to the guidance, 
withdraw the guidance, or pursue other regulatory actions, as appropriate.
To provide a clear policy for all stakeholders and FDA staff, the Agency is issuing this guidance 
to describe FDAs general recommendations for limited modifications to devices required to 
have an approved PMA or HDE to help address manufacturing limitations or supply chain 
disruptions.
FDA has determined that this guidance document presents a less burdensome policy that is 
consistent with public health. This guidance is being implemented without prior public comment 
because FDA has determined that prior public participation for this less burdensome policy is 
neither feasible nor appropriate (see section 701(h)(1)(C) of the Federal Food, Drug, and 
Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2)) because delaying this policy is likely to 
exacerbate ongoing supply chain issues. This guidance document is being implemented 
immediately, but it remains subject to comment in accordance with the Agencys good guidance 
practices.
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 
2Guidance Documents Related to Coronavirus Disease 2019 (COVID-19) (88 FR 15417), available at 
https://www.federalregister.gov/documents/2023/03/13/2023-05094/guidance-documents-related-to-coronavirus-
disease-2019-covid-19[hereinafter referred to as the COVID-19 Guidance Transition Notice].
2 Contains Nonbinding Recommendations
the word should in Agency guidances means that something is suggested or recommended, but 
not required.
II. Scope 
This policy applies to limited modifications made to a device approved through the PMA 
program that triggers the requirement that a manufacturer submit a PMA supplement or 30-day 
notice to FDA per section 515(d)(5)(A) of the FD&C Act and 21 CFR 814.39.3 
 
This policy also applies to limited modifications made to a device approved through the HDE 
program that require a manufacturer submit an HDE supplement or 30-day notice to FDA per 21 
CFR 814.108.4
Examples of such modifications may include, but are not limited to:
 Design and manufacturing changes to address component unavailability due to supply 
chain disruptions
 Manufacturing changes to allow the establishment to maintain operations and to 
accommodate social distancing in appropriate situations based on local conditions
 Changes in manufacturing facility or establishment
 Changes to packaging procedures
FDA intends this policy to help address current manufacturing limitations, potential shortages or 
supply chain challenges that may be alleviated or mitigated by adding production lines or 
manufacturing at alternative sites. Such sites may have different manufacturing equipment that 
can increase manufacturing capacity and supply and/or reduce supply chain interruptions and 
manufacturing bottlenecks. The policy set forth in this guidance does not apply to design or 
manufacturing changes made for reasons other than addressing manufacturing limitations or 
supply chain challenges.
III. Policy 
In issuing this policy, FDAs intent is to help foster the continued availability of medical devices 
after the COVID-19 public health emergency where a potential shortage, supply chain 
interruption, or manufacturing limitation exists. FDA believes this policy achieves this objective 
3FDAs interpretation of this section of the FD&C Act is discussed in the guidance documents 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, and 30-Day Notices, 135-Day Premarket 
Approval (PMA) Supplements and 75-Day Humanitarian Device Exemption (HDE) Supplements for Manufacturing 
Method or Process Changes, available athttps://www.fda.gov/regulatory-information/search-fda-guidance-
documents/30-day-notices-135-day-premarket-approval-pma-supplements-and-75-day-humanitarian-device-
exemption.
4For additional information regarding HDE supplements, refer to the guidance document Humanitarian Device 
Exemption Program, available athttps://www.fda.gov/regulatory-information/search-fda-guidance-
documents/humanitarian-device-exemption-hde-program.
3 Contains Nonbinding Recommendations
by exercising enforcement discretion concerning certain requirements that manufacturers must 
follow when modifications within the scope of this policy are made.
At this time, based on our current understanding, FDA does not intend to object to limited 
modifications to the manufacturing of devices approved through the PMA program or the HDE 
program, without prior submission of the required PMA or HDE supplement or 30-day notice, 
where the modification is necessary to address current manufacturing limitations, potential 
shortages or supply chain issues. This policy also applies to limited modifications to address 
current manufacturing limitations, potential shortages or supply chain issues that also result in 
changes to the performance or design specifications, circuits, components, ingredients, or 
physical layout of the device that trigger the requirement to submit a 180-day or real-time PMA 
supplement5 or a 75-day HDE supplement. Manufacturers should still verify any changes to 
confirm that they do not negatively affect the safety or performance of the device. In lieu of prior 
submission of a required PMA or HDE supplement, FDA does not intend to object to these 
limited modifications being implemented where manufacturers include a retrospective update in 
their next periodic report per 21 CFR 814.84(b)(1). 
Outlined below are examples of circumstances where FDA currently believes a modification 
may be needed to address current manufacturing limitations or supply chain issues and that may 
be within the scope of this policy. 
Component and Device Material Changes6:
 Component changes due to supply interruption of the component and a necessary 
software or firmware modification to accommodate such component changes.  
Examples of such a change include: 
o Changes made to microchips or other associated circuitry that meet or exceed 
existing performance specifications and testing plans such as:
 One component on a printed circuit board assembly (PCBA) being 
replaced with another that is the same package size and meets or exceeds 
the specification of the original component.
 A necessary software or firmware change related to replacing a 
component that impacts the subassembly but does not impact the 
finished device performance.
 A necessary hardware change related to replacing a component with 
another that meets or exceeds the specification of the original component 
but that is of different physical dimensions. 
 Device material changes due to changes in manufacturing methods or supply 
interruption. Examples of such a change include: 
o Changes made to non-tissue-contacting materials that meet or exceed existing 
performance specifications and testing plans. 
 
5For more information, see the guidance Real-Time Premarket Approval Application (PMA) Supplements, 
available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/real-time-premarket-
approval-application-pma-supplements.
6See 21 CFR 814.39(a).
4 Contains Nonbinding Recommendations
Manufacturing Procedures or Methods of Manufacture7:
 Supplier changes to maintain continuity in manufacturing where specifications are 
unchanged
 Equipment changes or equipment moves, including moves between clean rooms, to 
allow for processes to perform in equivalent manner to previously approved processes 
within the same facility
 Changes to accommodate social distancing in appropriate situations based on local 
conditions, such as modification of manufacturing processes to maintain or promote 
social distancing practices among employees/operators.
 Automation of existing processes that are fully verified
 Automation of certain processes, such as packaging and labeling processes to 
accommodate social distancing
 Modifications to increase capacity (e.g., addition of manufacturing lines, equipment 
modifications to process multiple components, and continuous processing) to meet a 
shortfall in existing facilities approved as part of an original PMA or HDE application 
or a supplement 
Site-Changes8:
 Change in manufacturing facility or establishment to an alternative site with an 
established and acceptable history of good manufacturing practices (GMP). Factors 
for an established and acceptable history of GMP include:
o Compliance with 21 CFR Part 8209 or similar quality system standard (e.g., 
ISO 13485),
o No concerning inspection observations (e.g., no official action indicated 
(OAI) inspectional outcomes) in the most recent FDA inspection,
o No significant recall history related to production or quality issues,
o No concerning medical device reports (MDRs), and 
o No history of regulatory misconduct. 
Alternative sites that are part of the Case for Quality (CfQ) Voluntary 
Improvement Program (VIP) would also be considered as a proxy for established 
and acceptable GMP.
7See 21 CFR 814.39(e), (f).
8See 21 CFR 814.39(c). See also the guidance Manufacturing Site Change Supplements: Content and 
Submission, guidance document available athttps://www.fda.gov/regulatory-information/search-fda-guidance-
documents/manufacturing-site-change-supplements-content-and-submission.
9On February 23, 2022, FDA proposed to amend the device QS regulation, 21 CFR part 820, to align more closely 
with international consensus standards for devices (87 FR 10119; available athttps://www.federalregister.gov/ 
documents/2022/02/23/2022-03227/medical-devices-quality-system-regulation-amendments). Specifically, FDA 
proposed to withdraw the majority of the current requirements in part 820 and instead incorporate by reference the 
2016 edition of the International Organization for Standardization (ISO) 13485, Medical devices- Quality 
management systems for regulatory purposes, in part 820. As stated in that proposed rule, the requirements in ISO 
13485 are, when taken in totality, substantially similar to the requirements of the current part 820, providing a 
similar level of assurance in a firms quality management system and ability to consistently manufacture devices 
that are safe and effective and otherwise in compliance with the FD&C Act. FDA intends to finalize this proposed 
rule expeditiously. When the final rule takes effect, FDA will also update the references to provisions in 21 CFR 
part 820 in this guidance to be consistent with that rule.
5 Contains Nonbinding Recommendations
In contrast, examples of changes FDA believes are outside the scope of this policy include but 
are not limited to the following: 
 Changes to the intended use of the device, including new indications for use of the 
device
 Changes to the labeling of the device that are outside the scope of changes related to 
the modifications described above 
 Changes to the sterility assurance level (SAL) or sterilization method
 Changes to reduce or eliminate quality control testing
 Automation of a manufacturing process that is not fully verified
 A change that affects the performance of the device, but is not caused by component 
unavailability
Such modifications are not within the scope of this policy and generally require submission of 
the applicable PMA or HDE supplement or 30-day notice.
Manufacturing and design changes must be performed in accordance with 21 CFR Part 820. 
Manufacturers must document any changes to the device in their device master record and 
change control records and make this information available to FDA, if requested, consistent with 
21 CFR 820.30 and 820.180. Component changes must be documented in accordance with 21 
CFR Part 820. Such records may include (depending on the specific change):
 Applicable standards to which the component conforms
 Software/firmware verification and validation
 Functional testing
 Mechanical testing (e.g., drop, vibration)
 Temperature testing (e.g., minimum storage, maximum storage, transport)
In the next periodic report (i.e., PMA or HDE annual report10) that is due after the modification, 
and in accordance with the PMA or HDE approval order for the device, FDA expects that the 
PMA or HDE holder will identify and describe any such modification(s).
As always, FDA will make case-by-case decisions regarding the enforcement of legal 
requirements in response to particular circumstances and questions that arise regarding specific 
changes to a device or device type. 
10For more information, see webpage, Annual Reports for Approved Premarket Approval Applications (PMA) 
available athttps://www.fda.gov/regulatory-information/search-fda-guidance-documents/annual-reports-approved-
premarket-approval-applications-pma.
6