The new article highlights the aspects related to the updated procedures to be reflected in a Modification Protocol as a part of marketing submission for medical devices utilizing machine learning technology.

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Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a draft guidance document dedicated to a Predetermined Change Control Plan (PCCP) to be submitted with respect to medical devices utilizing Artificial Intelligence (AI) and Machine Learning (ML) technologies. In particular, the document provides recommendations related to marketing submissions, as well as additional clarifications to be taken into consideration by medical device manufacturers 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 they intended to introduce new rules or impose new obligations. Moreover, 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 approach described in the guidance is intended to reduce the regulatory burden for the parties interested in placing their AI/ML-based products on the market and introducing changes thereto while ensuring the proper performance of such products and their continued compliance with any and all applicable regulatory requirements. As explained by the authority, when applying for marketing approval, a party responsible for a medical device may submit the aforementioned PCCP describing the changes the device will be subject to in the future. Once the PCCP is authorized by the FDA, the changes described therein will not require additional prior approval before being implemented. 

The document describes, inter alia, the content of the Modification Protocol section.

Update Procedures: Key Points

According to the guidance, the Modification Protocol section of a PCCP should provide a description of the update procedures describing the way the changes will be implemented and also the way information about such changes will be communicated to all the parties involved in order to ensure the device in question is used in a safe and efficient manner. As further explained by the FDA, the update procedures in a Modification Protocol should describe how manufacturers will update their devices to implement the modifications, provide appropriate transparency to users, and, if appropriate, update user training about the modifications and perform real-world monitoring, including notification requirements if the device does not function as intended pursuant to the authorized PCCP. According to the guidance, the said plan shall provide information on any labeling changes to be introduced following the implementation of the modification described therein. Under the general rule, the labeling shall at any time provide detailed enough directions for use to be followed in order to ensure the safety and effectiveness of the device, including the details on site-specific modifications. The authority additionally emphasizes the importance of ensuring labeling does not provide information on modifications that are not in place in the present version of the device, as this could mislead customers and create confusion. Should such information be included, the authority will deem the product to be misbranded.

FDA’s Expectations

As further explained by the FDA, the information associated with update procedures introduced by the manufacturer will be necessary for the authority to understand 1) how risks from implementing modifications may be mitigated by the update process, 2) how communication regarding the device updates will be provided to users (e.g., so that updates in device output results will be correctly interpreted by users); 3) how the device operation will remain available after the update; and 4) how all stakeholders will be kept up-to-date about device functionality and performance. Apart from this, the authority should also understand how the risks arising from the update process could be mitigated.


The guidance also describes in detail the scope of information the authority expects medical device manufacturers to provide with respect to update procedures. For this purpose, the authority provides an appendix illustrating the way update procedures should be described in a Modification Protocol to be included in the submission. According to the guidance, such information should include:

  • Confirmation that the verification and validation plans for the modified version of the device are the same as those that have been performed for the version of the device before the implementation of the modifications or identification of any differences between the two plans;
  • A description of how software updates will be implemented;
  • A description of how legacy users will be affected by the software update (if applicable); and
  • A description of how modifications will be communicated to the users, including transparency on any differences in performance, differences in performance testing methods, and/or known issues that were addressed in the update (e.g., whether there is an improvement in performance in a subpopulation of patients).

Apart from the above, the authority additionally emphasizes the importance of ensuring the communication related to performance changes is in line with the respective evaluation described in the Modification Protocol. 

In summary, the present FDA draft guidance describes in detail the approach to be applied when providing information about the updated procedures implemented by the medical device manufacturer. The document outlines the scope of information the authority expects the applicant to include in the respective section and also highlights the key points to be considered in this respect.

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