On October 24, 2023, the U.S. Food and Drug Administration (“FDA”), Health Canada, and the U.K.’s Medicines and Healthcare products Regulatory Agency (“MHRA”) jointly released a publication identifying five guiding principles for predetermined change control plans (“PCCP”) for machine learning-enabled medical devices (“MLMD Guiding Principles”).

The MLMD Guiding Principles are intended to help ensure the ongoing safety and effectiveness of devices in the face of change throughout the device’s total product lifecycle (“TPLC”) and promote international harmonization. FDA continues to issue guidance on health care technologies powered by artificial intelligence (“AI”) and machine learning (“ML”). The MLMD Guiding Principles draw upon the overarching Good Machine Learning Practice for Medical Device Development (“GMLP”) guiding principles, in particular principle 10, which states that deployed models are monitored for performance and re-training risks are managed. Recently, the FDA also issued draft guidance proposing Predetermined Change Control Plans to ensure that AI/ML-enabled medical devices can be safely, effectively, and rapidly modified, updated, and improved in response to new data.

The goal of the MLMD Guiding Principles themselves are not guidance for medical devices manufacturers; rather, they are intended to harmonize a framework on PCCPs for MLMDs among the FDA, Health Canada and MHRA and to establish policy considerations that will align across jurisdictions. Specifically, the MLMD Guiding Principles can help to align regulatory processes with the rapid and ongoing approach to change management in MLMDs; manage risks through monitoring, maintenance, and/or improving device performance; and uphold high regulatory standards to ensure device safety and effectiveness. FDA clarifies that the MLMD Guiding Principles refers to a PCCP proposed by a manufacturer, including one that specifies certain planned modifications to a device; the protocol for implementing and controlling those modifications; and the assessment of impacts from modifications.

The MLMD Guiding Principles are outlined below:

  1. Focused and Bounded: A PCCP describes specific changes that a manufacturer intends to implement. Such changes are limited to modifications within the intended use or intended purpose of the original MLMD. This characterization can include:
    • the extent of planned changes and scope of the MLMD with changes implemented
    • plans in place to safely modify the device within the bounds of the PCCP, including methods for verifying and validating the changes and mechanisms to detect and revert or stop implementation of a change that fails to meet specified performance criteria
    • the impacts of the planned changes
  2. Risk-based: The value and reliability of a PCCP is strengthened when the intent, design, and implementation of a PCCP are driven by a risk-based approach that adheres to the principles of risk management. This risk-informed perspective is relevant:
    • throughout the TPLC, from inception, through implementation and to use
    • to ensure that individual and cumulative changes remain appropriate over time for the device and its use environment
  3. Evidence-Based: Evidence generated throughout the TPLC of the device is important to:
    • ensure the ongoing safety and effectiveness of the device with a PCCP
    • demonstrate that the benefits outweigh the associated risks and
    • establish that the risks are adequately managed and controlled
  4. Transparent: For PCCPs, the best practice is to provide clear and appropriate information and detailed plans for ongoing transparency to users and other stakeholders. This helps ensure that stakeholders stay aware of the device’s performance and use before and after changes are implemented. Consider, for example:
    • characterization of data used in development and modifications, demonstrated to reflect the intended population
    • comprehensive testing for planned changes characterization of the device before and after implementation of changes
    • monitoring, detection, and response to deviations in device performance
  5. Total Product Lifecycle (“TPLC”) Perspective: Creating and using a PCCP from a TPLC perspective can:
    • elevate the quality and integrity of a PCCP by continually considering the perspectives of all stakeholders as well as risk management practices throughout the TPLC
    • use and support existing regulatory, quality, and risk management measures throughout the TPLC to ensure device safety by monitoring, reporting and responding to safety concerns

Takeaways

FDA’s publication of the MLMD Guiding Principles demonstrates the agency’s interest in stakeholder consensus on the core concepts of PCCPs. According to a press release, FDA is issuing these guiding principles to collaborate with international agencies and harmonize regulatory considerations of AI/ML technologies across jurisdictions. Device manufacturers, particularly those developing and deploying AI/ML-enabled devices globally, should consider how the principles align with their PCCPs for ML-enabled medical devices. They should also continue to follow updates on the PCCP draft guidance.

For more information, please contact the professionals listed below, or your regular Crowell Health Solutions contact.