FDA “PreCheck”? FDA Issues Draft Guidance on Predetermined Change Control Plans for Medical Devices

On August 22, 2024, the U.S. Food and Drug Administration (“FDA”) released a draft guidance entitled “Predetermined Change Control Plans for Medical Devices” (the “PCCP Draft Guidance”), which details FDA’s approach to implementing its statutory authority to clear or approve PCCPs as part of device premarket submissions. A PCCP authorized as part of a marketing submission provides device manufacturers with advanced clearance or approval for certain pre-specified modifications that would otherwise require a new marketing submission. The PCCP Draft Guidance discusses the types of modifications appropriate for PCCPs and the categories of information to include in a PCCP.

PCCPs are not a new concept. For example, FDA has previously addressed PCCPs for artificial intelligence/machine learning (“AI/ML”)-based software functions in a 2019 discussion paper and an April 2023 draft guidance (see prior Ropes & Gray Alert). In December 2022, as part of the Food and Drug Omnibus Reform Act, Congress granted FDA express authority to clear and approve PCCPs for all kinds of medical devices. Following this statutory reform, the PCCP Draft Guidance explains FDA’s approach to PCCPs for medical devices generally.

This Alert summarizes the key takeaways for manufacturers considering whether to include a PCCP in a future marketing submission, as well as notable issues for the industry to watch as FDA implements this program.

Guiding Principles for PCCPs

The PCCP Draft Guidance sets forth five guiding principles for PCCPs:

1. A PCCP should contain sufficient information to enable FDA to assess the reasonable assurance of safety and effectiveness or substantial equivalence of the device.
2. While PCCPs are optional, PCCPs may in some cases be the least burdensome means for bringing device modifications to market.
3. A PCCP becomes part of the marketing authorization of a device and will be included in FDA’s letter of authorization. Manufacturers must implement device modifications in a manner consistent with the authorized PCCP.
4. A PCCP “should include only a few, specific modifications that can be verified and validated” and not “a list of any/all modifications that a manufacturer may possibly make.” FDA cautions that it may not be able to authorize a PCCP that includes “numerous” modifications or modifications “that range across various aspects of the device.”
5. PCCPs are intended to harmonize with FDA’s existing guidance documents that address when a new marketing submission is required for device modifications—i.e., “Modifications to Devices Subject to Premarket Approval (PMA) – The PMA Supplement Decision-Making Process,” “Deciding When to Submit a 510(k) for a Change to an Existing Device,” and “Deciding When to Submit a 510(k) for a Software Change to an Existing Device” (collectively, the “Modifications Guidances”).

Establishing PCCPs and Labeling

A PCCP can be established along with the marketing authorization of a device and can be included in most types of PMAs and PMA supplements, traditional and abbreviated 510(k)s, and de novo requests. Following authorization of a PCCP, the manufacturer is later able to modify the device in accordance with the PCCP, rather than being required to obtain separate approval or clearance for the modifications. For devices authorized with a PCCP, publicly available device summaries, such as the PMA summary of safety and effectiveness and approval order, 510(k) summary, or de novo decision summary, should contain detailed descriptions of the PCCP.

As a general matter, apart from pure manufacturing changes, labeling for a device authorized with a PCCP should describe the PCCP and provide sufficient information for the user to understand the anticipated changes and continue to use the device safely and effectively following implementation of these changes. FDA generally recommends updates to PCCP information in the labeling to reflect any implemented modifications and the impact of such modifications on the device’s use.

Types of Modifications Appropriate for a PCCP

PCCPs should include only specific modifications that can be verified and validated and that are intended to maintain or improve the safety or effectiveness of a device. Modifications that do not require a new marketing submission in the first place are not appropriate for a PCCP and instead can be implemented directly in accordance with FDA’s Quality System Regulation. Furthermore, modifications described in a PCCP must not change the device’s intended use and must not result in the device no longer being substantially equivalent to the applicable predicate device (in the case of a 510(k)-cleared device). FDA cautions that PCCPs generally should not modify the indications for use of a device yet acknowledges there may be “certain” modifications to indications that may be appropriate for a PCCP, such as those specifying use with an additional device or component and those regarding home use.

Ultimately, whether a modification is appropriate for inclusion in a PCCP for a particular device involves a fact-specific analysis of, among other things, a device’s benefit-risk profile and the specific modification proposed. Certain modifications may be appropriate to include in PCCPs for some devices but not others, and some modifications may never be appropriate to include in a PCCP for any device. Although there are differences in the modifications that are permitted in a PCCP depending on the submission type, FDA states that PCCPs are generally not appropriate for the following types of modifications:

• Changes from general to specific use;
• Changes that may require new clinical data (though FDA notes that some changes requiring new clinical data such as method comparison data for in vitro diagnostics may still be appropriate for a PCCP);
• Changes that address recalls or safety issues; or
• Changes to a device constituent that impact the biologic or drug constituent part.

For 510(k) and de novo devices, FDA states that modifications that may significantly modify an existing risk can be included in a PCCP whereas those that may introduce a new risk are not appropriate for a PCCP. Manufacturers should evaluate modifications to be included in a PCCP in accordance with FDA’s Modifications Guidances, which will be updated based on the draft guidance, as applicable.

Contents of a PCCP

The PCCP Draft Guidance details the information that should be included in the three primary sections of a PCCP, which are generally consistent with the April 2023 draft guidance on PCCPs for AI/ML-enabled device software functions.

• In the Description of Modifications, manufacturers should enumerate with sufficient detail each individual modification that a manufacturer intends to make to a device and, for each modification, the rationale for the modification.
• The Modification Protocol should describe the methods, steps, and pre-defined criteria that manufacturers will use when developing, validating, and implementing the modifications identified in the Description of Modifications. The Modification Protocol should also clearly delineate which parts apply to each modification; FDA recommends using a traceability table for a PCCP with multiple modifications.
• The Impact Assessment documents the assessment of the benefits and risks of implementing the device modifications and how risks will be mitigated to assure the safety and effectiveness of the device in the intended population.

Key Takeaways and Issues to Watch

By enabling manufacturers to obtain pre-authorization for certain defined modifications to their devices, PCCPs present a valuable opportunity for manufacturers to deploy innovative modifications to devices more quickly while continuing to ensure the safety and effectiveness of marketed devices. Conversely, PCCPs also have the potential to increase submission complexity, which in some cases could delay an initial marketing authorization and potential launch. Disclosure of PCCPs in public documents could also have implications for manufacturers vis-à-vis competitive positioning and awareness in the marketplace of potential future product changes. Outlined below are key considerations for manufacturers in helping determine whether to pursue a PCCP.

PCCPs must be well tailored and specific; however, there remains considerable ambiguity regarding the appropriate number and type of modifications to include. The PCCP Draft Guidance acknowledges that PCCPs do not offer a one-size-fits-all approach for proposed device modifications and that PCCPs should “include only a limited number of modifications that are specific, and that can be verified and validated.” The draft guidance underscores that the number of specific modifications in a PCCP should be limited but does not set forth a maximum number of modifications permitted nor address whether the relatedness of the modifications would impact the number of modifications that are appropriate to include. Manufacturers will likely have to figure this out over time through discussions with FDA about specific PCCPs they are considering (e.g., Q-Submission meetings) or trial-and-error through actual PCCP submissions.

FDA’s implementation of PCCP reviews—and industry’s willingness to pursue PCCPs—remain open questions. Although the Agency has to date authorized several dozen devices with PCCPs based on an analysis by a former FDA official, FDA and industry are still determining how to best leverage PCCPs. The development, review, and authorization of PCCPs as a part of marketing submissions for new devices will require significant effort from both FDA and manufacturers prior to submission. This upfront work will hopefully result in the ability to implement modifications more expeditiously, but time spent preparing and reviewing a PCCP could mean that submissions are filed later than planned. As a cautionary note, other regulatory programs that were intended to expedite the premarket review process such as FDA’s 510(k) Third Party Review Program have not been widely used to date. It remains to be seen whether PCCPs will become a commonplace pathway for introducing device modifications and, if so, which modifications and device types for which they will most often be used.

Using a predicate device in a 510(k) that was cleared with a PCCP may pose practical challenges. For 510(k) submissions that use a predicate device that has been cleared with a PCCP, FDA’s substantial equivalence analysis will compare the subject device to the predicate device without any of the modifications specified in the PCCP. Manufacturers will therefore need to ensure that the version of the predicate device used in support of a 510(k) substantial equivalence determination does not include any PCCP modifications. This could be difficult in practice, depending on the extent to which the PCCP for the predicate device is described in the device labeling or the publicly available 510(k) summary. To date, PCCPs have not been consistently described in either such that they could be easily identified.

FDA engagement regarding PCCPs is strongly encouraged. FDA encourages manufacturers to engage with the applicable FDA review division through the Q-Submission Program early in development regarding their proposed PCCPs such that feedback can be incorporated prior to submission. Early engagement with FDA is especially encouraged for manufacturers proposing PCCPs for combination products and high-risk, life-sustaining, life-supporting, or implantable devices.

Comments to the PCCP Draft Guidance are due by November 20, 2024. If you have any questions regarding this Alert or would like assistance in preparing comments, please contact any member of the Ropes & Gray FDA Regulatory practice or your usual Ropes & Gray advisor.