AI-Enabled Device Software Functions: FDA’s Final Guidance for Predetermined Change Control Plans

­­­­On December 4, 2024, the U.S. Food & Drug Administration (FDA) released its Marketing Submissions for a Predetermined Change Control Plan (PCCP) for Artificial Intelligence-Enabled Device Software Functions (AI-DFS) final guidance document (“PCCP Guidance” or “final guidance”). The final guidance discusses the scope of applicability of PCCPs, policy behind PCCPs, and the major components necessary to include in submissions for PCCP approval.

Below are some fundamental questions answered by the PCCP Guidance:

What Are PCCPs?

PCCPs allow device manufacturers to implement preapproved modifications to their devices in lieu of obtaining separate authorizations for each significant change prior to implementation. A PCCP describes what modifications will be made based on the continued learning of AI-DFS and how those modifications will be implemented.

How Does the Final Guidance Align with the Draft Guidance? 

FDA’s final guidance recommendations largely align with draft guidance issued in April 2023 and build off input collected from multiple Advisory Committee Meetings, Public Workshops, and comments on the draft guidance. The PCCP Guidance is nonbinding and does not replace, modify, or expand on existing law. However, it offers insight into how the FDA considers regulation of AI-DFS, FDA’s current thinking on submission requirements, and how manufacturers and developers can best utilize PCCPs.

What is the Scope of Applicability of PCCPs?

Contrary to draft guidance, which focused only on machine learning (ML), a subset of AI-DFS that uses techniques to continually train algorithms to improve performance based on data, the final guidance applies to all AI-DFS. Despite this, the new final PCCP Guidance is still most applicable to ML-enabled devices that would benefit from preapproved modifications based on continued learning. Further, although the guidance is applicable to combination drug-device products, the final guidance emphasizes that PCCPs generally apply only to the device component of a combination product.  

The PCCP Guidance addresses how a premarket authorization for an AI-DSF with a PCCP can be established through many application pathways, including the Premarket Approval (PMA) pathway for high-risk devices, the traditional 510(k) pathway for lower risk devices, and the De Novo pathway for novel devices. Despite significant pushback from commentors, PCCPs are not permitted for use in special 510(k) applications, which is an optional pathway for certain well-defined device modifications where a manufacturer modifies its own legally marketed device, and where design control procedures produce reliable results that can form, in addition to other 510(k) content requirements, the basis for substantial equivalence. Further, although manufacturers are allowed and encouraged to discuss their PCCP plans with FDA through a pre-submission process, the PCCP Guidance clarifies that FDA does not authorize the PCCP during this stage. We strongly recommend that manufacturers discuss their PCCP plans with FDA to ensure that there is agreement on the requirements and regulatory pathway.

Components of PCCPs in Applications

PCCPs must include three essential components: (1) a description of the modification, (2) modification protocol, and (3) impact assessment.

The PCCP Guidance provides several core components of the description of a modification that should be included within a PCCP and the types of modifications that FDA anticipates will be appropriate for inclusion. The proposed description must address whether the modifications will be automatic or manual, meaning whether the modifications will be implemented automatically with a software update or whether the modifications require some human intervention, action, and/or decision-making. Further, the modification description should specify whether the modifications are “global,” meaning they apply uniformly to all devices or whether they are applied “locally,” meaning applied differently based on unique characteristics of patients or clinical sites. If the AI-DFS will be applied locally, the manufacturer must justify the heterogenous treatment. Finally, manufacturers must describe the expected frequency of updates or modifications.

The PCCP Guidance anticipates that the following three types of modification are appropriate for inclusion in a PCCP:

1. Modifications related to quantitative measures of AI-DSF performance specifications
2. Modifications related to device inputs to, and compatibility with, the AI-DSF
3. Certain modifications related to the device’s use and performance

The PCCP Guidance anticipates that modifications must generally maintain the device within its intended use and indications as is necessary to remain substantially equivalent to the predicate device. However, the PCCP Guidance specifies that there may be certain modifications to the indications that are appropriate for inclusion within a PCCP. The PCCP Guidance does not elaborate on which modifications to the indicated uses may be appropriate for inclusion, however.

In addition to a description of the modification, manufacturers must include a modification protocol in their PCCPs. A modification protocol describes the methods that will be implemented when developing, validating, and implementing proposed modifications. The PCCP Guidance notes that a modification protocol should include predefined acceptance criteria used to verify and validate modifications to ensure continued device safety and efficacy. To this end, the PCCP Guidance identifies four components of a modification protocol that should be included within a PCCP:

1. Data management practices
2. Retraining practices
3. Performance evaluation protocols
4. Updated procedures, including communication and transparency to users and real-world monitoring plans as applicable

Finally, documentation of PCCPs should include an impact assessment of the benefits and risks associated with implementing post-approval modifications as well as how the manufacturer intends to mitigate potential risks.

Additional Considerations

In addition to addressing key components of PCCPs, the PCCP Guidance highlights several additional components to consider when developing PCCPs. The PCCP Guidance discussed the importance of labeling to ensure that consumers are aware of the potential for post-market modifications of an AI-DSF. Labels for AI-DSF with approved PCCPs must explain that the device incorporates ML and has an authorized PCCP so that consumers are aware of the need for periodic software updates and how to ensure continued efficacy of their AI-DSF.  

The PCCP Guidance also discusses when it may be necessary to modify the PCCP if additional modifications are being considered for an AI-DSF. FDA anticipates that modifications to PCCPs will require a new marketing submission because of the risk that the modified PCCP may significantly affect the safety or efficacy of the device. In other words, changes to the PCCP would constitute a change to the underlying AI-DSF that would require subsequent FDA approval. Again, due to the nature of certain modifications, we recommend that before moving down the development pathway, it is a best practice to discuss the planned modifications with FDA staff.

Why the PCCP Guidance Matters

The final guidance is important because it outlines how manufacturers may implement preapproved modifications to their devices in lieu of obtaining separate authorizations for each significant change prior to implementation, which would be arduous and time consuming for manufacturers.

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