The new article describes in detail the aspects related to the applicability of recommendations provided in the guidance in terms of medical devices and regulatory pathways.

The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a draft guidance document dedicated to the regulatory requirements for a predetermined change control plan (PCCP) to be submitted in the context of medical devices utilising artificial intelligence/machine learning (ML) technologies. Once finalized, the document will provide additional clarifications regarding the applicable regulatory requirements, as well as recommendations to be followed by medical device manufacturers (software developers) and other parties involved in order to ensure compliance thereto. At the same time, provisions of the guidance are non-binding in their legal nature, nor are intended to introduce new rules or impose new obligations. Moreover, the authority explicitly states 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. 

In particular, the guidance describes the regulatory approach to be applied with respect to Machine Learning – Device Software Functions (ML-DSFs) that could be subject to changes in the course of further improvement and development of the device. According to the guidance, its scope covers ML-DSFs for which modifications to the ML model are implemented automatically (i.e., for which the modifications are implemented automatically by software), as well as for ML-DSFs for which modifications to the ML model are implemented manually (i.e., involving steps that require human input, action, review, and/or decision-making, and therefore are not implemented automatically). 

Scope: Key Points

The approach described in the guidance is considered to be the least burdensome and beneficial in terms of further development of the products based on innovative technologies while ensuring compliance with the applicable regulatory requirements in terms of safety and effectiveness when used for the intended patient population. In particular, the document provides additional recommendations regarding the information to be included in the PCCP being a part of a marketing submission for such devices. According to the guidance, the term “PCCP” refers to a plan that includes device modifications that would otherwise require a premarket approval supplement, De Novo submission, or a new premarket notification. The authority also mentions that a plan that contains only minor modifications that would not require a new submission is outside the scope of this guidance. With respect to the regulatory status of the changes to software-based products and the way it should be determined, the authority refers to the respective guidance documents dedicated to changes to existing software-based products and the decision-making process associated thereto. Once the PCCP included in the marketing submission has been reviewed by the authority, its status will be “authorized PCCP”. 

As explained by the authority, by including a PCCP in a marketing submission, manufacturers can proactively pre-specify and seek premarket authorization for intended modifications (and their method of implementation) to an ML-DSF without necessitating additional marketing submissions for each modification delineated and implemented in accordance with the PCCP. Thus, the main purpose of the said plan being included in the marketing submission is to describe the way modifications to the ML-based product would be implemented. 

Under the general rule, should modifications have the potential to affect the safety and effectiveness of a medical device, a premarket authorization will be required for such modifications to be implemented, unless they are initially covered by a PCCP. 

As it was mentioned before, PCCP could be submitted in the context of applications under 510(k), PMA, or De Novo pathways, being considered a part of the technological characteristics of the device. Since the comparison of technological characteristics constitutes an important element of the 510(k) process, including the determination of substantial equivalence, PCCP should be taken into consideration as well. In particular, the authority states that in making a determination of substantial equivalence where the predicate device was authorized with a PCCP, the subject device must be compared to the version of the predicate device cleared or approved before changes made under the PCCP. 

Specific Aspects

According to the guidance, recommendations provided therein should also be applied with respect to medical devices being constituent parts of combination products when they are themselves or contain ML-DSF. In such cases, the authority encourages manufacturers to get in touch with the relevant departments before submitting an application in order to obtain additional clarifications and ensure the submissions contain all the information the authority will need to complete its review. 

Early engagement will also be beneficial in case of high-risk, life-sustaining, life-supporting, or implantable devices placed on the market under one of the frameworks described herein. 

The authority also mentions that the recommendations provided in the present guidance are not exhaustive, while the description of the information to be included in a PCCP provided in this guidance should not be considered complete. Furthermore, the authority will review a PCCP submitted by the applicant and provide case-specific recommendations or requests based on the results of such a review. At this stage, the authority will also assess the nature of the changes described by the applicant in order to determine their eligibility for being included in a PCCP. 

In summary, the present guidance outlines the scope of information the authority expects applicants to include in a PCCP submitted when applying for marketing approval for the product containing a machine learning device software function. The document explains the approach to be applied when determining the details to be included and also provides additional recommendations to be considered. 

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