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Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a draft guidance document dedicated to the requirements for a Predetermined Change Control Plan (PCCP) for medical devices utilising Artificial Intelligence/Machine Learning (AI/ML) technologies. In particular, the document provides recommendations to be considered in the context of marketing submissions, as well as additional clarifications regarding the regulatory requirements set forth under the existing legal framework. At the same time, the authority explicitly states that provisions of the guidance and recommendations provided therein are non-binding in their legal nature, nor are intended to introduce new rules or impose new obligations. Moreover, an alternative approach could be applied, provided such an approach is in line with existing legislation and has been agreed with the authority in advance.
The scope of the guidance covers the most important aspects related to AI/ML-enabled device software functions (ML-DSFs). The concept of a PCCP described in the guidance is intended to reduce the regulatory burden for the parties involved in operations with innovative products. In particular, existing legislation prescribes that for the changes included in a PCCP reviewed and authorized by the FDA additional marketing approval will not be required.
Identifying a PCCP
In accordance with the guidance, when an application for marketing approval is submitted, a plan described therein should be included as a standalone section. Apart from that, it should be also referred to in the table of content and cover letter accompanying the submission. As further explained by the FDA, the PCCP should be discussed in the marketing submission as part of the device description, labeling, and relevant sections used for determining substantial equivalence or reasonable assurance of safety and effectiveness. Should any information related to the said plan be provided in other sections of the submission, the appropriate references should be added accordingly.
Under the general rule, labeling used for a medical device should meet any and all applicable requirements set forth by the respective regulations. In particular, the authority additionally emphasizes the importance of including the directions for use to be considered in order to ensure the safety and proper performance of a medical device. In certain cases, the authority may require a PCCP to address the matters related to labeling and information to be included therein. According to the guidance, for ML-DSFs with an authorized PCCP, the labeling should explain that the device incorporates machine learning and has a PCCP so that users are aware that the device may require the user to perform software updates and that such software updates may modify the device’s performance, inputs, or use. It is also mentioned that the information included in the labeling should be sufficient for potential users to understand the changes and the impact they could have.
Authorized PCCP and Change Implementation
The document further explains how an authorized PCCP should be used when implementing modifications to a medical device. Under the general rule, a PCCP reviewed by the authority as a part of a marketing submission becomes a part of marketing authorization for the respective product. Under the general rule, a PCCP should be evaluated within the existing risk management framework of the device and implemented in accordance with the manufacturer’s quality system.
In order to assist medical device manufacturers (software developers) with interpreting provisions of the applicable legislation and following the requirements set forth therein, the authority provides a flowchart describing the way modifications to a medical device should be implemented based on a PCCP already authorized by the FDA. According to the said flowchart, as the very first step, medical device manufacturers should consider whether the planned changes are in line with the respective authorized PCCP and covered by the Description of Modification being a part of it. Should it be determined that the changes are consistent with the authorized PCCP, such changes could be implemented without additional marketing authorization required. In such a case, these changes should be implemented in accordance with the Modification Protocol, and also be duly documented.
At the same time, should it be determined that the proposed changes are falling outside the scope of an authorized PCCP, a new marketing submission will be required before such changes will be allowed for implementation. Consequently, if the modification is not consistent with the authorized PCCP – including if the specific modification is not included in the authorized PCCP or if the modification is included in the authorized PCCP but is not implemented in accordance with the methods and specifications described in the Modification Protocol – the manufacturer should then proceed to evaluate the modification in accordance with applicable laws and regulations and the device modifications guidances, if applicable, and proceed accordingly. Hence, should it be determined that the new marketing submission is required, it should be submitted by the party responsible for the device in question before the modified version will be placed on the market. According to the guidance, a marketing submission associated with the planned modifications could include information on the changes themselves, and also on the way they are to be implemented. It is also mentioned that for the original authorized PCCP to apply to the modified device, the manufacturer must include the proposed PCCP in the marketing submission for the device modification; the PCCP is reviewed and established as part of the review of the modified device.
In summary, the present guidance document issued by the FDA describes in detail the approach to be applied when implementing changes to an AI/ML-based product in order to comply with the respective regulatory framework. The document pays special attention to the information to be included and the way it should be provided.
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