Intro: Pre-Determined Change Control Plans in medical device regulation

• Post-market updates to authorized medical devices may, or may not, require a new submission to the FDA. The core process for deciding whether a modification to a device needs to be submitted either through a new marketing application or a supplement (in the case of devices authorized under a Pre-Market Approval (PMA) application) is laid out in a series of three guidance documents. This includes final guidance from 2008 on “ The PMA Supplement Decision-Making Process” and two 2017 guidance documents informing modifications to devices under a 510(k) pre-market notification (one general modifications guidance and another on software updates). This trio of documents are known collectively as the Modifications Guidance documents.
• Pre-Determined Change Control Plans (PCCPs) represent another way of conducting updates. The general concept of a PCCP is for a device sponsor to submit a series of planned modifications to a medical device, including information on how it would validate, verify, implement and monitor the modifications, to the FDA as part of a marketing application. This would, theoretically, allow FDA to pre-authorize certain modifications to a device. PCCPs were first conceived of as a way to leverage artificial intelligence/machine learning (AI/ML) that would need to be updated over time. In 2019, the agency issued a Discussion Draft on a potential regulatory assessment framework for AI/ML devices that highlighted the specific issues raised by these technologies, including the use of PCCPs.
• In late 2022, the FDA gained new authority related to PCCPs. As part of the Food and Drug Omnibus Reform Act (FDORA), Congress clarified new statutory definitions related to the development and regulation of PCCPs for medical devices. Specifically, under section 3308 of the legislation, Congress clarified that changes authorized under a PCCP, which would represent the types of significant modifications to an authorized device that would otherwise necessitate a new regulatory submission to FDA, “shall not be required” if they are within the scope of the established PCCP.
• In March 2023, the FDA issued its initial draft guidance on PCCPs, and specifically PCCPs for machine learning-enabled device software functions (ML-DSF), or the function of a device that leverages ML. That draft guidance introduced the concept of PCCPs formally for the first time. It defined key terms and offered initial thinking on what would – or would not – be a good use case for modifications to a device under a PCCP. As would be expected, this draft guidance focused primarily on the use of PCCPs for AI/ML enabled product, but did offer an initial framework of what a PCCP would look like in practice, including how they should be designed and submitted, how they will be reviewed by the agency, and what the post-market expectations are for a device modified under a PCCP.
• Expansion of the concept of PCCPs has been a priority for the agency – and industry. As reflected in both the comments on the ML-DSF draft guidance and CDRH’s 2024 guidance agenda, there was a broad expectation that FDA should issue guidance on using PCCPs for more device types than ML-DSF. Per the CDRH guidance agenda, the agency expected to finalize the ML-DSF guidance in 2024, as well as issue draft guidance on PCCPs for medical devices that are not, specifically, AI/ML devices.

New PCCP Draft Guidance: For all device types

• On August 21, 2024 the FDA released a new guidance document on PCCPs that outlined recommendations for all medical devices, and not just AI/ML-enabled devices.
• The scope of the new guidance: “This draft guidance recommends that a PCCP describe the planned device modifications, the associated methodology to develop, validate, and implement those modifications, and an assessment of the impact of those modifications,” FDA wrote. The guidance covers PCCP content and process for all device types and for all medical device marketing application types.
• The guidance does have some specific areas of focus, though. While the guidance applies broadly to all device types, the agency includes a couple of key use-cases for PCCPs in the guidance document, and in particular related to diagnostics. Still, “this draft guidance is not intended to delineate a comprehensive list of modifications FDA would consider appropriate for inclusion in a PCCP for a device,” FDA wrote.
• How does this new version compare to the guidance on PCCPs for ML-DSF? Many of the same concepts are represented in both guidance documents, and they’re structured similarly. However, as expected, this new draft guidance offers information on PCCPs that applies more broadly and is not specifically focused on AI/ML-related PCCPs. This means that it’s got broader applicability, with less language and content specifically focused on AI/ML issues (e.g., model drift). The overall idea of the PCCP and its consideration align between the two guidance documents – as do the definitions, process, and content expected in a PCCP.
• In short: Those familiar with the ML-DSF PCCP guidance should be generally familiar with the content of this new draft guidance.
• At a high level: What is a PCCP? PCCPs are plans, submitted with marketing authorization requests, to make certain changes or modifications to a product under the authorization. PCCPs are comprised of three main components (detailed more below): the Description of Modifications, Modification Protocol and Impact Assessment. In effect, a “PCCP includes those device modifications that generally would otherwise require a new marketing submission. These modifications include those that could significantly affect, or that otherwise affect, the safety or effectiveness of the device, unless those modifications are covered by an authorized PCCP.”
• The PCCP is authorized as a part of the marketing authorization, and a device sponsor “obtaining FDA authorization of a PCCP as part of a marketing submission… allows a manufacturer to modify its device over time in accordance with the PCCP instead of obtaining separate FDA authorization for each significant change prior to each implementation.” Like making a major modification without a new marketing submission or supplement, making changes outside of the scope of a PCCP could result in the device being adulterated and misbranded.
• How PCCPs would apply: A PCCP can be authorized through the PMA pathway, 510(k) pre-market notification pathway, or De Novo classification request pathway. For devices cleared under a 510(k) with a PCCP, the version of the device “cleared or approved prior to changes made under the PCCP” would be able to serve as a predicate for a 510(k). Similarly, once such a modification made in compliance with a PCCP is submitted and authorized under a modification application (which is not necessary for the purpose of implementing the change), then that version of the device can be used as a predicate.
• For combination products, the guidance would apply specifically to the device constituent part of a device-led combination product – a PCCP could not be authorized as part of a drug submission for a drug- or biologic-led combination product. Notably, trade association PhRMA had specifically asked in its comments on the ML-DSF draft PCCP guidance for the FDA to “specifically confirm that sponsors have the flexibility to submit a PCCP as part of the NDA or BLA for drug-device or biologic-device combination products and that a separate device marketing submission is not required in order to submit a PCCP for the device constituent part of such products.” However, this does not appear to be the case.
• Least burdensome: The agency notes that leveraging a PCCP “may be a least burdensome option” to support device modification. While the system remains voluntary and optional, the use of a PCCP may reduce the overall need for supplements or new submissions.

Building a PCCP and maintaining it over time

• “PCCPs are specific,” the agency clarifies. PCCPs should “include specific modifications that the manufacturer intends to make over time” but should not list all the modifications that a manufacturer “may possibly make.” Per the agency, sponsors should include “only a few, specific modifications that can be verified and validated” in a PCCP; it goes on to note that the FDA “may not be able to make” an authorization decision if the PCCP includes “numerous modifications, or modifications that range across various aspects of the device.”
• What application types can sponsors use to establish a PCCP? As described above, PCCPs may be appropriate for devices under a PMA, 510(k) or De Novo classification request. However, it does not need to be an original PMA – PCCPs can also be established through a variety of PMA and supplement submission types (including Modular PMAs, in which a PCCP would be a module, and different supplements). For example, a PCCP comprising a manufacturing change could be submitted as a 135-day supplement, while a minor change that FDA agrees can be achieved in real-time review can be submitted via a Real-Time PMA supplement. For 510(k)s, PCCPs can be established through either the Traditional or Abbreviated 510(k) submission pathways. Only original De Novo requests can be used, however (which makes sense, because there is no other De Novo type).
• A quick note about following a PCCP – or not. As noted above, implementing changes outside of the scope of a PCCP would be considered the same, in a regulatory sense, to implementing a modification without authorization (i.e., the product as modified would be adulterated or misbranded). However, the agency notes that simply not implementing a change under a PCCP is fine: “FDA would not consider it to be a deviation from the authorized PCCP in situations where a manufacturer chooses not to implement modifications in their authorized PCCP or where a manufacturer chooses to submit a new marketing submission for a device modification in lieu of using their authorized PCCP” (footnote 34).
• As the PCCP is a technological characteristic, how is this considered in a review of substantial equivalence? For products submitted with a PCCP under a 510(k): “In general, FDA anticipates that the PCCP will primarily be reviewed after FDA finds that the intended use of the subject device and the predicate device are the same, to help determine whether the devices have different technological characteristics that do not raise different questions of safety and effectiveness.”
• The PCCP in a marketing submission: A focus on labeling. PCCPs should be “a standalone section within the marketing submission” and be “prominently included and discussed in the cover letter” and table of content. It should also be discussed throughout the application – including in the labeling. The new draft guidance offers some additional information about how PCCPs should be addressed in labeling, noting that “information on the device’s authorized PCCP may be necessary for a user to understand changes in the device and to continue to use the device safely and effectively across the intended use populations and intended environments as the device changes pursuant to the authorized PCCP.” Information on PCCPs should also be available, “in sufficient detail,” in public-facing information about the device (e.g., device summaries).
• The FDA has some specific asks for PCCP-related labeling, including that labeling should include a statement disclosing the PCCP and the PCCP itself include labeling updates that would be implemented as modifications to the device are made under the PCCP. This includes information on the implemented modifications (“including a summary of current device performance, associated inputs/outputs, validation requirements, and related evidence”), how the modifications were implemented, and a description of how users will be informed of the modifications (e.g., updated instructions for use or version history).
• Using an authorized PCCP to make a modification: In general, “FDA would consider it to be a deviation from the authorized PCCP in circumstances where the PCCP is not followed or cannot be followed”; this includes circumstances in which a modification is not included in their PCCP (in which device modifications guidance should be followed) or a change that is within scope is implemented using a process (methods and specifications) outside of what was described in the Modification Protocol of the authorized PCCP. In these circumstances, the sponsor can either request a modification to the PCCP or they can seek a device modification. If going the second route (i.e., new marketing submission with a modification), then “the manufacturer must also submit the proposed, modified PCCP for the device.”
• Modifying an authorized PCCP: As with the original authorization of a PCCP, modifications to an authorized PCCP “will generally constitute changes to the device that would otherwise require a new marketing submission” – typically a 510(k), special 510(k) or a PMA supplement. As in the ML-DSF guidance, the agency would want to see a new marketing submission that includes “a summary of the changes to the authorized PCCP, and where practicable, a tracked changes version compared to the authorized PCCP.” Further, (see footnote 70), when the primary change leading to the need for a new marketing submission is to modify a PCCP, “in general, manufacturers may provide references in the marketing submission to prior marketing submissions for content that remains unchanged, as appropriate.” Again, as in the ML-DSF guidance, the agency notes it will “focus its review on the aspects of the device that are most significantly modified.”
• Version control and maintenance: The FDA seems to be expecting a bit of a learning curve with PCCPs, stating that it expects “interactive” reviews of marketing submissions with a PCCP “as manufacturers gain experience developing and implementing PCCPs.” For now, the agency says it will leverage its existing processes for interactive reviews – or, potentially, through issuing a deficiency letter. This means that PCCPs might be modified while they’re under review, and the agency notes that “a final, revised version of the PCCP should be submitted as a clean copy to FDA” with titles and version numbers. The PCCP (and specific version) are authorized with the device, so “a manufacturer should only have one version of an authorized PCCP for their device” – but new versions can be authorized over time.
• This section of the guidance also describes some practical information, like how the FDA intends to look at new marketing submissions for products modified under a PCCP (it does not intend to re-review the adequacy of modifications made under a PCCP), and that modifications made under a PCCP authorized in a PMA should be reported under the PMA Annual Report (and include any updated labeling, as applicable).

PCCP Policy: Types of modifications under a PCCP

• Not all modifications are appropriate for a PCCP. In general, those that are “intended to maintain or improve the safety or effectiveness of the device” and can be “verified and validated” are a good fit for a PCCP. Further, modifications that would alter a device’s intended use, or its indications for use, are likely not appropriate for a PCCP as “FDA believes that most modifications to the indications for use included in a PCCP would be difficult for FDA to assess prospectively to determine whether the device would remain safe and effective.” The agency urges sponsors to submit a Q-submission to discuss potential modifications.
• Notably, there are some exceptions to the general idea that PCCPs can’t be used to change the labeling or indications for use, clarified in a list of potentially appropriate PCCP use cases later in the document (and again for devices under PMA). These include potential changes to the labeling that focus on “a specific subset of patient population within the originally indicated patient population” (emphasis added), adding information in the labeling/indication for use to specify use of the device with an additional “device, component, or human genetic variant” or updating the device specifically for home use settings.
• The guidance describes both general recommendations for manufacturers to consider whether their planned modifications are appropriate for a PCCP, and provides some examples. These are intended to work with the guiding principles (outlined above) – but does note that “Ultimately, decisions about the types of modifications to be included in a PCCP are generally fact-specific for each device.”
• For a 510(k) or De Novo device: In general, modifications under a PCCP for these devices should maintain the device’s intended use. However, “a significant change or modification in design, material, chemical composition, energy source, or manufacturing process may be appropriate for inclusion in a PCCP,” the agency describes, and refers sponsors back to the 510(k) Modifications guidances (for both general changes and software changes). The agency aligns its policy on PCCP-appropriate modifications with those guidance documents, recommending the same general process (see, for example, this flowchart from those guidance documents carried over to this guidance). Specifically, it asks sponsors to conduct a risk-based assessment to determine if a marketing submission would be necessary. For the purposes of a PCCP, a modification that could introduce new risk “are generally not appropriate for inclusion in a PCCP,” but modifications that might modify existing risks “generally may be appropriate for inclusion in a PCCP” when there is adequate risk mitigation between the device’s risk management framework and the manufacturer’s Quality System.
• The agency offers a list of “certain high-level modifications that generally may be appropriate or are not appropriate for inclusion in a PCCP.” Those that might be appropriate include changes to design (dimensions, performance specifications, wireless communication, components/accessories, user interface), sterilization, transport, expiration dating or packaging (using well-established methods), materials or components (including reagents), software changes related to compatibility or interoperability, software changes to improve device performance, “certain changes to the labeling” to discuss “a specific subset” of the patient population, changes to the labeling or indication for use to specify device use with another device (or component, or human generic variant), or indications for use to allow the device to be used in the home setting. Those that are not appropriate include changes to control mechanisms, design changes that alter the intended use, changing a device from single use to reusable, change or remove contraindications, change from prescription to over-the-counter (OTC) use, changes in indication from general to specific, adding a new patient population, those updates that might need clinical data, changes to address safety issues or changes to a device constituent part that “impacts” a drug or biological part.
• Quick note: There’s a brief carve out specifically for IVDs. While the list above states that changes requiring clinical data are generally not appropriate for inclusion in a PCCP, “Certain changes that may need new clinical data, such as method comparison data for IVDs, may be appropriate for inclusion in a PCCP” (footnote 90).
• PCCP modifications appropriate in a PMA Application or Supplement: Similar to the process for 510(k)s, “modifications included in a PCCP must maintain the device within the device’s intended use” although “other modifications that could affect the safety or effectiveness of the device may be appropriate for inclusion in a PCCP.” Per the guidance, these types of changes can include minor changes and manufacturing changes, which “generally may be appropriate for inclusion in a PCCP when the risks of implementing the modification” are mitigated by the risk management framework and the manufacturer’s QS. Again, the agency pulled some of this content from its guidance on modifications for devices subject to PMA (including this flow chart).
• It also provides a list of examples, differentiating between what is a minor change and what is a manufacturing change. This list generally reflects those that are outlined above, repeated for content on PMAS – minor changes related to materials/components (e.g., new sources for reagents), labeling changes that describe a specific subset of patients within the original indication, or software updates to improve device performance or update interoperability. Manufacturing changes would include those to sterilization, joining or cleaning, changes that can automate existing processes, changes to the “environmental conditions” or “certain changes in methods of manufacture.” Changes that are not appropriate would be those that are significant changes, changes to add new patient populations to the indication/intended use, changes that may need clinical data (except IVDs, see above), to address a safety issue, or to “add, expand, or move the manufacturing or sterilization site of a finished device.”

PCCP Policy: Content

• As noted above, there are three main components of a PCCP: the Description of Modifications, the Modification Protocol, and the Impact Assessment.
• Description of Modifications: A PCCP will need to describe “each planned modification” – including information the “specific changes to the device characteristics and performance” from the modifications. This should describe and enumerate the, as previously mentioned, specific individual proposed modifications, the justification for each modification, and “presented in the level of detail that permits understanding of the specific modifications that will be made to the device.”
• Modification Protocol: This is the component of the document that will describe the methods for “developing, validating, and implementing the modifications” as planned, including full descriptions of the verification and validation activities. “Documentation of modifications verified and validated per the Modified Protocol must be compliant with the Quality System Regulation (QSR), including that the manufacture must document the change in accordance with the manufacturer’s quality system.” The protocol should describe the specifics of modifications, including “appropriate and applicable data, test methods, analysis methods, and specified acceptance criteria used to develop, validate, and implement all proposed modifications” and the process by which they would be implemented (including plans for communication and training on users). It should also include a plan for recordkeeping, risk mitigation strategies, and “be least burdensome” for review. The agency describes the different components of the protocol, including both performance evaluation methods (how to ensure the device will stay within the device’s specifications) and update procedures (the actual plan for implementing a modification). There should also be traceability in the submission, with each part of the Protocol mapped to the Description of Modifications.
• Impact Assessment: “An Impact Assessment in a PCCP is the documentation of the assessment of the benefits and risks of implementing a PCCP for a device, as well as the mitigations of those risks,” the FDA wrote. It should be based around the manufacturer’s existing quality system. The documentation in a PCCP should include a comparison between the versions of the device (original and under every modification), the benefits and risks of each modification, the verification and validation activities’ ability to reasonably ensure safety and effectiveness, how individual modifications might impact each other and the cumulative impact. In effect, this is the section of the PCCP that should contextualize what each modification will do, how they might interact, and how each modification will impact the overall functionality of the device.

Analysis and what’s next

• The guidance concludes with a list of illustrative examples related to situations in which a PCCP might be appropriate for certain devices – including for diagnostics. These include adding new sample types or extending stability claims for a test, or changing sterilization methods from an established category A to an established category B. While the list is certainly more comprehensive than was available in the ML-DSF guidance, it’s likely that manufacturers will seek more, and more detailed, information on illustrative examples.
• When this guidance is final, it will update the considerations on whether to submit a new 510(k) or PMA supplement. When the PCCP policy is fully implemented, it will represent a significant change to the currently available avenues to modify a medical device. The FDA’s assertion is that PCCPs will be the least burdensome option for device modifications, which typically require a new marketing application. However, we’ll likely need to see the full implementation of this policy to understand if, and when, that’s the case – or whether certain types of modifications (e.g., sterilization changes, shelf life or stability claim updates, cybersecurity updates, digital health updates, IVD kit updates) lend themselves better to PCCPs than other types of modifications.
• FDA leadership has touted the idea of PCCPs for IVDs updates or sterilization changes – both areas facing upheaval after recent policy changes. For IVDs specifically, it’s likely that the diagnostic test industry will seek more nuanced, specific guidance related to IVDs. As the guidance is currently drafted, IVD-specific considerations are sometimes pulled out of the recommendations in the guidance (e.g., some PCCP-appropriate modifications can include clinical data), but additional guidance on the specifics of how the policy can be leveraged for IVD use cases would likely be helpful. For example, guidance specifically on adding sample types, swapping out reagents or requesting a shelf life extension for a test under a PCCP.
• Process wise: CDRH will need to make Level 2 (clarifying existing process) updates to its existing guidance on “Deciding When to Submit a 510(k)” for a device or for a software change to a device, as well as its guidance on “The PMA Supplement Decision-Making Process” – and “we may also make Level 2 updates” to the PCCP for AI/ML guidance document “and other device-specific guidance documents containing information on PCCPs for consistency.”
• The FDA is expecting a learning curve here, indicating in the guidance that it expects this to be an “interactive” process while developers and sponsors are still building experience with the PCCP process. Industry has been actively seeking more information about how they can use PCCPs, but the actual implementation of the policy is likely to be a challenge for device developers navigating the new modification process – including both submitting PCCPs and tracking them over time once the device is on the market and in distribution, and under a modification. For example, the guidance notes that “if the labeling states that a modification to the device has been implemented when it has not, the device might be deemed misbranded” (footnote 109). While industry had specifically touted the potential use case for electronic labeling in feedback on the ML-DSF draft guidance (see AdvaMed’s comments), the new draft guidance does not address this issue, despite it being a high priority for industry.
• Further, the intricacies of reviews with PCCPs going forward are likely to be challenging. FDA says it “does not intend to re-review the adequacy of modifications implemented consistent with an authorized PCCP” but the specifics of a review for a device that is several versions from its originally authorized version, with multiple PCCPs/supplements, will be an organizational challenge down the line.
• Also: what is a good or a not good fit for a PCCP still needs to be worked out. While the agency provides some principles and a list of examples, it also says that “Ultimately, decisions about the types of modifications to be included in a PCCP are generally fact-specific for each device.” The agency notes that if PCCP review is what’s holding up an application’s authorization, it may authorize the submission if the PCCP is withdrawn, but a better understanding of what types of modifications, and how they’re expected to be appropriate tracked, documented and monitored over time will be critical to the success of this policy.
• A quick note: Q-sub reliance. The draft guidance is, like the ML-DSF version of the PCCP guidance, highly reliant on the Q-submission process. Multiple times throughout the guidance, the agency urges sponsors to submit a Q-submission to flag their approach in developing their PCCP for regulators. Notably, this is a common refrain from the FDA when implementing a new policy, or when the foundation of a policy relies on “case-by-case” determinations. However, this is not a particularly efficient system; As ThermoFischer Scientific noted in its comments on the ML-DSF draft guidance, “too much flexibility within the review process leads to a lack of transparency and consistency during the decision-making process from the agency,” citing their concerns about “overdependence on Q-submissions” in that guidance.
• And a final quick note: eSTAR. As many commenters noted in the ML-DSF draft guidance docket, CDRH is moving towards requiring submissions in its electronic submissions template and resource (eSTAR). On August 22, FDA finalized guidance that would require all De Novo applications to be provided in eSTAR format as of October 2025. Many commenters had flagged concerns about navigating the new content type of PCCPs in eSTAR – which will need to be addressed going forward as it becomes mandatory for more submission types.

To contact the author of this item, please email Laura DiAngelo ( ldiangelo@agencyiq.com).
To contact the editor of this item, please email Alexander Gaffney ( agaffney@agencyiq.com)

Key Documents and Dates

• Predetermined Change Control Plans for Medical Devices: Draft Guidance for Industry and FDA Staff
• FDA guidance webinar: September 3, 2024
• Electronic Submission Template for Medical Device De Novo Requests: Guidance for Industry and Food and Drug Administration Staff
• AgencyIQ Analysis: FDA’s Pre-Determined Change Control Plan draft guidance: Terminology, content and policy