The new article highlights the aspects related to the applicable policy and outlines the key points to be taken into consideration.
The Food and Drug Administration (FDA), the US regulating authority in the sphere of healthcare products, has published a draft guidance document dedicated to the content of a Predetermined Change Control Plan (PCCP) for artificial intelligence/machine learning (AI/ML) – based medical devices. In particular, the document provides additional recommendations to be considered in the context of marketing submissions for ML-enabled device software functions (ML-DSFs). Once finalized, the document will provide non-binding clarifications and recommendations based on the existing regulatory framework in order to assist medical device manufacturers (software developers) in ensuring compliance with the applicable regulatory requirements. The authority also mentions that an alternative approach could be applied, provided such an approach is in line with the existing legislation and has been agreed with the authority in advance.
The guidance describes, inter alia, a policy to be applied with respect to the said plans, and also highlights the key points to be addressed therein.
The authority acknowledges that due to the specific nature of ML-based products, they should undergo certain changes when used. In this respect, it is vitally important to ensure their continued safety and proper performance, while the applicability of the standard change control policy is limited due to the way ML products evolve.
As it was previously mentioned, by using a PCCP, medical device manufacturers may utilize the least burdensome approach – according to the applicable regulatory requirements, the changes described in a PCCP will not require separate approval.
In certain cases, deviations from a PCCP approved by the authority (authorized PCCP) could take place. The FDA mentions that in case such deviations could potentially affect the safety or effectiveness of the product, they would most likely require a new marketing submission. The authority additionally emphasizes that in such cases, further distribution of a product without a new marketing submission filed would be considered adulteration and misbranding, which are prohibited acts under the applicable legislation, creating grounds for legal or regulatory actions to be initiated against the parties responsible for a medical device in question.
The document further describes in detail the key components of a PCCP and highlights the key points associated thereto. According to the guidance, the said plan should consist of:
- a detailed Description of Modifications;
- A Modification Protocol; and
- An Impact Assessment.
As explained by the authority, these components would provide the informant sufficient for it to complete the review of modifications proposed, including the assessment of their potential impact on the safety and effectiveness of a medical device. According to the guidance, the detailed Description of Modifications should outline the modifications that will be made to the ML-DSF, and the Modification Protocol should describe the verification and validation activities (including pre-defined acceptance criteria) that will support those modifications; while the Impact Assessment helps to tie the Description of Modifications to the Modifications Protocol in that the Impact Assessment identifies the benefits and risks introduced by the specified, planned modifications and how the verification and validation activities of the Modification Protocol will continue to assure the safety and effectiveness of the device. The FDA further states that all the three abovementioned components of a PCCP should coexist.
Establishing a PCCP
In accordance with the existing regulatory requirements, a PCCP could be included in a submission under one of the frameworks being 510(k) premarket notification, De Novo, or PMA pathways. Furthermore, it should be subject to review by the authority before the medical device manufacturer will take any actions based on it, implementing changes to the products. In the case of a 510(k) pathway which requires establishing a substantial equivalence, the comparison should be made to the version existing before the changes have been implemented.
The manufacturer may also introduce a new PCCP for a product already placed on the market with the respective PCCP being reviewed by the FDA. Should it be the case, a new PCCP should be included in a marketing submission. When reviewing the information provided, the authority will pay the most attention to the significant changes in comparison to the initial version. For instance, should the product itself remain relatively intact with a new plan being submitted, the authority will pay attention to the new plan.
According to the guidance, since an authorized PCCP is a technological characteristic of the authorized device with which it was established; if the authorized device is significantly modified other than as specified in the authorized PCCP, a new marketing submission is required for the significantly modified device. Thus, in order for the initial plan to be applied to a medical device subject to changes, such a plan would require an additional review.
The authority also encourages the parties responsible for medical devices to apply for feedback before filing a new submission. In particular, for this purpose, the Q-Submission pathway could be utilized. At the same time, the FDA additionally emphasizes that while manufacturers are encouraged to discuss their plans through a Pre-Submission, PCCPs are not authorized in Pre-Submissions.
In summary, the present FDA guidance outlines the content of a PCCP to be included in an application for marketing approval related to a medical device containing ML-enabled device software functions. The document also pays special attention to situations when there is an intent of a medical device manufacturer to make changes to a PCCP already authorized by the FDA.
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