The U.S. Food and Drug Administration (FDA or its agencies) recently issued draft guidance titled “Marketing Submission Recommendations for Predetermined Change Control Plans for Artificial Intelligence/Machine Learning (AI/ML) Enabled Device Software Capabilities.” has been issued. The draft guidance follows passage of the Food and Drug Administration Reform Act (FDORA) of 2022, which the FDA grants premarket approval (PMA) or premarket notice (510(k)).1 While the FDORA provision covers all devices covered by PMA or 510(k), the draft guidance does not address machine learning-enabled device software features (ML-DSF) that manufacturers expect to change over time. Especially applicable.
PCCPs are intended to include planned changes that require new marketing submissions under applicable FDA regulations if not otherwise included in the PCCPs.2 If a PCCP is approved, manufacturers of ML-DSFs are not required to submit new marketing applications before implementing changes described and made in accordance with the approved PCCP.
PCCP establishment and modification
A PCCP must be reviewed by the FDA and established as part of a marketing authorization before a manufacturer can implement changes under the PCCP.Therefore, a PCCP is a marketing application (i.e., a 510(k), PMA, or de novo classification request).
Manufacturers wishing to establish a new PCCP for previously approved devices must include the proposed PCCP in their marketing submission along with other appropriate marketing submission requirements for the device. Importantly, an approved PCCP applies only to the approved device version for which it was established. Therefore, if an approved device is substantially modified in a way that requires a new marketing submission, the original approved PCCP must be applied to the substantially modified device. must be reviewed and established as part of the new marketing submission for the device. .
Additionally, FDA anticipates that the modified PCCP will need to be reviewed and established as part of the new marketing application. Therefore, a manufacturer wishing to change his PCCP for a device previously approved using a PCCP will need to submit a new marketing application containing the proposed PCCP along with other appropriate marketing application requirements for the device.
Contents of PCCP
The PCCP should include a change description, change protocol, and impact assessment components.
• Change description
The PCCP change description section identifies “specific planned changes to ML-DSF that manufacturers intend to implement,” and provides detailed descriptions of “changes in device characteristics and performance resulting from implementation of the changes.” must be included. FDA recommends that “PCCPs should include only a specific, limited number of changes to allow for verification and verification.”
Types of modifications that may be acceptable for inclusion in a PCCP include:
- Changes related to quantitative measurements in the ML-DSF performance specification.For example, improving analytical and clinical performance by retraining ML models on new data within the intended population from the same type and range of input signals
- Changes related to device input to ML-DSF. For example, extension of algorithms to include new sources of the same signal type (such as different makes, models, or versions of data acquisition systems), or limited changes related to new types of signals.input
- Limited modifications related to device use and performance (e.g., for use within certain subpopulations that were not previously available)
The changes contained in the PCCP should keep the device within its intended range of use, and the FDA further states in the draft guidance:[a]At this time, FDA expects the changes contained in the PCCP to keep the device within its intended use.
• modified protocol
The change protocol should describe the methods (and pre-defined acceptance criteria) to follow when developing, validating, and implementing changes to maintain the safety and effectiveness of the device. The change protocol outlines the manufacturer’s data management practices, retraining practices, performance evaluation tools, and update procedures (including communication and transparency to users, and real-world monitoring plans) for each change to the PCCP. Contains components.
The PCCP should clearly explain which parts of the change protocol apply to each change within the change description. This can be achieved through traceability tables for PCCPs with multiple changes.
• Impact evaluation
Finally, the PCCP should include an impact assessment, or documentation of the benefits and risks of implementing PCCP in ML-DSF, and an assessment of the mitigation of such risks.
An impact assessment should:
- Compare the device version with each change implemented to the device version without the change implemented.
- Discuss the benefits and risks (including risks of social harm) of each change
- Discuss how the activities proposed within the modification protocol continue to provide reasonable assurance of device safety and efficacy
- Address the impact of implementing one change on implementing another change
- Address the overall impact of implementing all changes across devices, not just ML-DSFs
FDA recognizes that for some devices it may be appropriate to include impact assessment content within the modified protocol rather than as a separate section of the PCCP.
Additional points for manufacturers of ML-DSFs
Importantly, as FDA emphasized in its April 13, 2023 webinar, the draft guidance is not intended to be a complete description of what must be included in marketing submissions for ML-DSFs. Instead, the agency will allow the FDA’s Office of Review to determine “whether the scope of the amendment is appropriate for inclusion in the PCCP and what evidence and information is required to support the proposed amendment in the marketing application.” It says that
FDA encourages manufacturers to work early with FDA to discuss proposed PCCPs and utilize the Q-Submission process to obtain feedback from the agency.
Interested stakeholders may submit comments on the draft guidance to the docket (FDA-2022-D-2628) by July 3, 2023.
[1]Consolidated Appropriations Act of 2023, Pub. L. No. 117-328, § 3308 (2022).
[2]21 CFR § 807.81(a)(3) or 21 CFR § 814.39(a).
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