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FDA recently released its final guidance<\/a> for Predetermined Change Control Plans (PCCPs) for Artificial Intelligence-Enabled Device Software Functions (AI-DSF). The final guidance hasn\u2019t changed much from the draft guidance with respect to the type of modifications FDA considers applicable for a PCCP and the required components of a PCCP (see our prior blog post on the draft guidance here<\/a>).\u00a0 The most noteworthy change is the title, which has been broadened to include AI-DSF, not just the subset of AI known as machine learning (ML). FDA defines Artificial Intelligence (AI) as a \u201cmachine-based system that can, for a given set of human-defined objectives, make predictions, recommendations, or decisions influencing real or virtual environments.\u201d\u00a0 Machine Learning is defined as a \u201cset of techniques that can be used to train AI algorithms to improve performance at a task based on data.\u201d\u00a0 Consistent with the title change, the draft guidance\u2019s references to ML-DSF have been replaced with AI-DSF, \u00a0which is now defined as a \u201cdevice software function that implements an AI model\u201d and omits references to ML models and techniques.<\/p>\n As we\u2019ve previously blogged, a PCCP is a mechanism established by Congress under the Food and Drug Omnibus Reform Act (FDORA) to streamline post-market changes to medical devices. Sponsors can include a PCCP as part of their pre-market submission that describes an approach for making certain types of device modifications after the device is marketed. If FDA agrees to the PCCP, such changes can be made without a supplemental marketing submission.<\/p>\n While a PCCP can address many types of post-market device changes, FDA specifically recognizes that software development is an iterative process, and software developers continually try to improve and update devices. Therefore, this guidance builds on FDA\u2019s commitment to \u201cdevelop and apply innovative approaches to the regulation of [AI-enabled devices].\u201d<\/p>\n Scope of Permissible PCCPs<\/em><\/strong><\/p>\n The final guidance describes the scope of post market modifications to AI-DSF that are appropriate to include in a PCCP. In general, a modification must be within the device\u2019s intended use and maintain the indications for use in order to be included in a PCCP. The final guidance does leave some \u2018wiggle room,\u2019 stating that \u201ccertain modifications to the indications for use\u201d may be appropriate for inclusion in a PCCP. Examples of modifications to AI-DSF that may be appropriate for a PCCP include modifications to inputs, input sources, compatibility, and interoperability. However, the guidance states that FDA will evaluate a PCCP on a case-by-case basis, in light of the \u201cbenefit-risk profile\u201d of the specific device when deciding if the proposed modification can be authorized in the marketing application, noting that \u201ccertain modifications that may be appropriate for inclusion in a PCCP for one device may not be appropriate for inclusion in a PCCP for another device.\u201d The guidance encourages sponsors to engage with FDA using the Q-Submission Program prior to submitting a PCCP in order to obtain FDA feedback on if the proposed modification is suitable for inclusion in a PCCP and what information the PCCP will need to include.<\/p>\n Consistent with the draft guidance, the final guidance takes the position that PCCPs are only appropriate for the following submission types:<\/p>\n Unfortunately, the final guidance continues to exclude Special 510(k)s (see our prior blog post here<\/a>). In fact, eSTAR does not allow a PCCP to be included in a Special 510(k); attempting to do so results in the message \u00a0\u201cif you are establishing a PCCP this should not be done in a Special 510(k).\u201d\u00a0 Modifications to previously authorized PCCPs can be submitted via a Special 510(k), and eSTAR recommends that the manufacturer submit a clean copy and redline of the PCCP as an attachment.<\/p>\n The final guidance emphasizes the importance of having a quality system in place, stating that FDA \u201cmay under certain case-by-case circumstances withhold clearance of a PCCP submitted in a 510(k) based on findings in the regulatory history of the manufacturer that demonstrate failure to comply with [Quality System regulation (QSR)].\u201d \u00a0An analogous limitation is contained in the Special 510(k) guidance<\/a>, which states that a Special 510(k) should not be submitted if the manufacturer has received a violative inspection report following a recent QS inspection that identified \u201cobservations related to design controls that are relevant to the design changes.\u201d We wonder if the Agency will similarly reject a PCCP if a manufacturer has demonstrated a failure to comply with design controls, especially those related to design changes.<\/p>\n Components of a PCCP <\/em><\/strong><\/p>\n The guidance identifies the following elements for inclusion in a PCCP:<\/p>\n Modification Description <\/em><\/p>\n The Modification Description should describe the planned modification and the performance specifications. FDA recommends including only a \u201climited number\u201d of modifications in the PCCP. The description should be sufficiently specific to allow verification and validation as defined in the Modification Protocol. The manufacturer should, in addition to stating whether the modification will be implemented manually or automatically, include details such as:<\/p>\n Modification Protocol<\/em><\/p>\n The Modification Protocol should describe the methods for developing, verifying, validating, and implementing the modifications described in the Modification Description. Manufacturers should develop the Modification Protocol consistent with their quality system and should follow their risk management processes. FDA expects four elements to be included in a Modification Protocol:<\/p>\n FDA may request additional information during the review of the PCCP.<\/p>\n For most manufacturers, verification and validation protocols may only cover performance evaluations against pre-determined acceptance criteria, and they may need to pull data management practices and re-training practices from their development plans. Verifying and validating update procedures may be in a separate protocol from performance testing and should be included in the Modification Protocol section of the PCCP. Update practices and training of end users also need to be addressed.<\/p>\n Data management practices should include how the manufacturer plans to obtain and use training, tuning, and test data to support each AI-DSF modification. FDA provides definitions for the three datasets. Although data scientists sometimes refer to the tuning dataset as the \u2018validation dataset,\u2019 FDA encourages using terminology consistent with the Agency\u2019s Artificial Intelligence Glossary<\/a>.\u00a0 Test data should be independent of the training and tuning data and come from multiple sites representing the intended use population.<\/p>\n Re-training practices should identify the \u201cobjective of the re-training process,\u201d describe the AI model and the AI-DSF modification, and identify any \u201ctriggers for re-training.\u201d<\/p>\n Performance evaluation protocols should include the planned verification and validation activities for each AI-DSF modification separately and, in total, including all planned modifications. This will ensure each AI-DSF modification does not have an adverse impact on the overall device performance. The Modification Protocol should \u201caffirmatively state that if there is an unresolvable failure<\/em> in performance evaluation for a specific modification (e.g., the predefined acceptance criteria for a specific modification are not met), the failure(s) will be recorded, and the specific modification(s) will not be implemented.\u201d The final guidance clarifies that only an \u201cunresolvable failure\u201d should preclude implementation; if the failure is resolvable the modification may be implemented after retesting. Additionally, a failure is NOT considered unresolvable \u201cif a root cause analysis of the failure reveals it is not related to specific aspects of the PCCP.\u201d\u00a0 In such cases, performance testing may be conducted again.<\/p>\n The update procedures should include how the AI-DSF modifications will be implemented and communicated to end users. The update procedures should include plans for required labeling changes and training provided to end users. The final guidance added information on updating the UDI as part of the planned labeling changes when there is a new version of the device. In addition, the final guidance recommends the Modification Protocol include the manufacturer\u2019s \u201cpost-market surveillance plans and procedures,\u201d\u00a0 which reflects a change from the draft guidance\u2019s recommendation for \u201creal-world monitoring.\u201d The final guidance adds that such post-market surveillance plans \u201cmay include real-world monitoring and notification requirements if the device does not function as intended pursuant to the authorized PCCP.\u201d Post-market surveillance plans and procedures (PMS) are a requirement under ISO 13485 which will be adopted into FDA\u2019s Quality Management System Regulation in 2026. PMS requires manufacturers to gather information from various sources, evaluate the data for trends, and integrate the data into product development, risk management and design updates. This change in language seems to suggest a more formal approach to monitoring to ensure the modified AI-device remains safe and effective.<\/p>\n FDA recommends that the PCCP include a traceability table containing each proposed AI-DSF modification and the location within the Modification Protocol for each of the four elements described above.<\/p>\n Impact Assessment<\/em><\/p>\n The Impact Assessment documents the benefits and risks of implementing the AI-DSF and the mitigations for the identified risks. The Impact Assessment should:<\/p>\n The final guidance goes beyond considerations of harm and includes unintended bias when discussing the benefits and risks of the modification. The guidance states that the Impact Assessment can be a stand-alone document, incorporated into the manufacturer\u2019s Risk Assessment, or included in the Modification Protocol.<\/p>\n The final guidance includes references to combination products and indicates the Impact Assessment should address the impact of the device modification to the biologic or drug constituent part. In fact, the final guidance includes an example of a combination product in Appendix B.<\/p>\n Post Authorization<\/em><\/strong><\/p>\n When FDA grants marketing authorization for a device that includes a PCCP, the PCCP will be referenced by title and version number in the authorization letter. Details of the PCCP will be publicly available (i.e., PMA summary of safety and effectiveness document (SEED) and approval order, 510(k) Summary, De Novo decision summary). FDA recommends that the following information be made public regarding the PCCP as appropriate: planned modifications, testing methods, validation activities and performance requirements to meet before implementation, and means by which users will be informed of the implementation of the modification.<\/p>\n Modifications that deviate from the authorized PCCP and are implemented without a market authorization may render the device \u201cadulterated and misbranded\u201d and result in enforcement action by FDA, including \u201cseizure on injunction.\u201d<\/p>\n If you need to modify the PCCP, you must submit a revised PCCP to the FDA for authorization prior to implementing the modification. As stated previously, when submitting a revision to an authorized PCCP, you should provide both a clean copy and redline of the revised PCCP and also include a reference to the submission that authorized the prior version of the PCCP.<\/p>\n The final guidance hasn\u2019t changed much from the draft guidance with respect to the type of modifications eligible for a PCCP or the required components of a PCCP. Consistent with the draft guidance, it contains a significant level of detail on the fundamental principles that should govern the design and development of AI-based software. The placement of this information is odd and would seem to fit better in the recently released draft guidance<\/a> on AI-DSFs: Lifecycle Management and Marketing Submission Recommendations (Lifecycle Management guidance), which we blogged about here<\/a>. Unlike the PCCP guidance, which is focused specifically on post-market changes, the ostensible focus of the Lifecycle Management guidance should be a comprehensive foundation for the design and development of AI-enabled devices. Manufacturers of AI-based software would expect to find this level of detail in the Lifecycle Management guidance would not think to look for additional details in the PCCP guidance. Ideally, the Lifecycle Management guidance would have been finalized before the PCCP guidance, however since that is not the case, it would seem to make sense to transfer design and development information from the PCCP guidance into the Lifecycle Management guidance or, at the very least ensure the Lifecycle Management guidance cross-references the PCCP guidance, where applicable. In HPM\u2019s next blog we will take a deep dive into setting up a successful data management strategy, which is critical to achieving market authorization for both the device and any associated PCCPs.<\/p>\n<\/div>\n\n","protected":false},"excerpt":{"rendered":" FDA recently released its final guidance for Predetermined Change Control Plans (PCCPs) for Artificial Intelligence-Enabled Device Software Functions (AI-DSF). The final guidance hasn\u2019t changed much from the draft guidance with respect to the type of modifications FDA considers applicable for a PCCP and the required components of a PCCP (see our prior blog post on […]<\/p>\n","protected":false},"author":1,"featured_media":4302,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[97],"tags":[12908,7001,35796,2408,6897,44462,15878,39807,3824,13319,44461,10933,44460,10766],"dealstore":[],"offerexpiration":[],"class_list":["post-92811","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-legal","tag-adds","tag-change","tag-closely","tag-control","tag-details","tag-ditches","tag-draft","tag-fdas","tag-final","tag-guidance","tag-pccp","tag-plan","tag-predetermined","tag-sticks"],"yoast_head":"\n\n
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