In April of 2023, the FDA published the draft guidance, “Marketing Submission Recommendations for a Predetermined Change Control Plan for Artificial Intelligence/Machine Learning (AI/ML)-Enabled Device Software Functions.” In this preliminary guidance, the FDA presented a forward-thinking strategy rooted in scientific principles to guarantee the safe, efficient, and swift adaptation, enhancement, and refinement of AI/ML-powered devices.
Although all of this all sounds intimidating, our goal is to break down the most significant parts of the Predetermined Change Control Plan (PCCP) for manufacturers to better understand this complex guidance.
What is a Predetermined Change Control Plan (PCCP)?
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The Predetermined Change Control Plan (PCCP), is an innovative approach to address ML-related risk in premarket submissions for medical devices. This plan empowers manufacturers to refine and tune AI/ML algorithms through frequent deployments within the constraints of safety and effectiveness without the need to make an additional premarket submission. What does this mean in practical terms? It translates to a significant reduction in time and resources required by manufacturers and regulators in preparing and reviewing premarket submissions for software changes.
The utilization of PCCP is meant to reduce regulatory burden by providing the means for real-time improvements in devices - post-market. The flexibility to adapt and enhance without excessive bureaucratic hurdles is pivotal in enabling advancements in medical device technology.
The FDA has designated the acronym ML-DSF (machine learning-enabled device software function) to describe this specific AI use in the medical industry.
The focus on ML-DSF and the adoption of approaches like the PCCP represents a pivotal shift in the regulatory paradigm, fostering innovation and efficiency while maintaining the high standards of safety and efficacy in medical device development.
In order to understand the PCCP, first you need to understand why it is necessary in the AI/ML space.
To begin, artificial intelligence (AI), and more specifically, the AI subset of machine learning (ML), is a new and powerful tool companies around the world are beginning to integrate into their medical device systems in order to be more efficient and productive. The FDA recognizes the importance of AI/ML in the medical industry and is trying to create a process to allow companies to develop safe and effective medical devices that use ML models trained by ML algorithms.
Since, by definition, ML-DSF’s are constantly changing and improving themselves, the FDA has created the PCCP guidance to allow ML-DSF manufacturers to follow these guidelines instead of constantly creating new submissions for medical device modifications that would otherwise require a premarket approval supplement, such as a Special 510(k), De Novo Submission, or PMA supplement. In the FDA’s words, “This draft guidance proposes a least burdensome approach to support iterative improvement through modifications to an ML-DSF while continuing to provide a reasonable assurance of device safety and effectiveness.”
How to Create a PCCP
The PCCP draft guidance includes three main sections:
- Description of Modification: Itemization of the proposed device modifications, along with specific justifications for the ML-DSF modifications.
- Modification Protocol: Describes the means, methods, and manner to develop, validate, and implement these changes.
- Impact Assessments: Entails documenting the evaluation of benefits and risks associated with implementing a PCCP for an ML-DSF, along with strategies to mitigate those risks.
With the proper knowledge, team, and IT systems, manufacturers are able to create a compliant PCCP for their ML-DSF. Below, we will discuss each section of the PCCP.
PCCP Description of Modifications
Purpose of a Description of Modifications
This section is a description of each planned modification to a ML-DSF in the PCCP as either a stand-alone submission or in concert with a “new” premarket submission. For modifications to an approved PCCP, FDA recommends that a PCCP include “only a limited number of modifications that are specific, and that can be verified and validated.”
How to Complete Description of Modifications
Modifications to the PCCP that are difficult to verify and validate due to circumstances such as overly complex modifications, lack of specificity or clarity, or insufficient data or testing methods may impact the approval of the PCCP. By limiting the number of modifications, the FDA can concentrate their review efforts on a defined set of changes. This focused approach enables thorough scrutiny and assessment of each modification's impact on the device's performance, safety, and effectiveness.
The Description of Modifications should itemize the proposed device modifications, along with specific justifications for the ML-DSF modifications. To facilitate comprehension, labeling changes associated with these modifications should be detailed separately in a Modification Protocol. The details should be sufficient for understanding the nature of the planned changes and should link each modification to a specific performance evaluation activity.
It is essential to indicate if the modifications are automatic (implemented by software) or manual (requiring human intervention). This distinction becomes crucial in the FDA's assessment, especially concerning the substantial equivalence or safety and effectiveness of the modifications. Additionally, it should specify whether modifications will be uniform across all devices or differ based on unique clinical site conditions or individual patient characteristics.
Modifications suitable for a PCCP are those aimed at maintaining or enhancing device safety or effectiveness. Acceptable modifications may include quantitative performance enhancements, expansions in device inputs, or limited changes for specific subpopulations. All modifications should align with the device's intended use and maintain its indications for use.
The FDA will assess PCCPs considering the specific device's benefit-risk profile, proposed modifications, and its experience applying these policies across different device types.
PCCP Modification Protocol
Purpose of Modification Protocol
The purpose of the modification protocol is to establish a comprehensive set of procedures, delineating the step-by-step process for implementing the aforementioned protocol modifications while ensuring continued device safety and effectiveness. This includes the documentation describing the methods that will be followed when developing, validating, and implementing modifications delineated in the Description of Modifications section of the PCCP. The Modification Protocol also includes V&V activities that shall be performed (including pre-defined acceptance criteria).
How to Complete Modification Protocol
While the Description of Modifications outlines planned changes, the Modification Protocol describes the means, methods, and manner to develop, validate, and implement these changes. The goals include identifying methods, acceptance criteria, and data used for modifications. This ensures generated information aligns with regulatory requirements, mitigating identified risks, and being efficient for both manufacturers and FDA review.
These goals include:
- Identify the methods and data used to develop, validate, and implement all proposed modifications
- Identify the test methods, data, statistical analyses, and specified acceptance criteria for all proposed modifications
- Ensure that the information that would otherwise be generated and submitted to the Agency (i.e., if the modifications were implemented on a device that did not have an authorized PCCP) will be generated by the manufacturer for each modification and maintained consistent with recordkeeping requirements and in accordance with the manufacturer’s QMS.
- Ensure that the risks that have been identified in the Impact Assessment as related to modifications detailed in the Description of Modifications (including the update process and communication to users) will be mitigated
- Be least burdensome for the manufacturer to develop and for FDA to review. This includes being traceable and specific to the modifications detailed in the Description of Modifications section and sufficiently comprehensive to support specific modifications.
PCCP Impact Assessment
Purpose of the PCCP Impact Assessment
The Impact assessment entails documenting the evaluation of benefits and risks associated with implementing a PCCP for an ML-DSF, along with strategies to mitigate those risks. The manufacturer conducts this assessment within the existing quality system (design control) framework.
The Impact Assessment, included in the marketing submission, is structured to:
- Compare modified versus unmodified device versions
- Discuss benefits and risks of each modification, including social harm risks
- Ensure that activities in the Modification Protocol maintain device safety and effectiveness
- Evaluate inter-dependencies among modifications and the collective impact of all modifications (and other device modifications or not)
How to Complete the PCCP Impact Assessment
Manufacturers should document how individual modifications affect not only the ML-DSF but also the device's overall functionality, including other software functions and hardware. Additionally, for multiple function device products, manufacturers should consider including relevant information following FDA guidance to assess impacts effectively. It is also necessary to account for the device's critical quality attribute to ensure the device is performing at the same, or a better metric with the ML-DSF modification.
What do Medical Device Companies Need to Know About PCCP Submissions?
The PCCP process involves a periodic regulatory review of the manufacturer’s plan for maintaining the safety and effectiveness of a device. These include:
- A first time PCCP approval
- For deviations from an approved PCCP
- When ML-DSF modifications or protocol changes significantly impact the device’s safety and effectiveness
The FDA says, “Premarket authorization for an ML-DSF with a PCCP must be established through the pathway, De Novo pathway, or PMA pathway, as appropriate, as a PCCP must be reviewed and established as part of a marketing authorization for a device prior to a manufacturer implementing any modifications under that PCCP.”
A big mistake medical device companies make with regards to a new PCCP submission is thinking all they need to do is create a new process. A new process is necessary, however, in order to create a compliant PCCP, companies also need the correct IT system that will allow the new process to be efficiently and effectively tracked and executed.
How Ketryx Can Help Manufacturers & Developers with their PCCP
Ketryx helps companies operationally comply and release software at the speed allowed by their PCCP by enabling developers to utilize modern development tools and practices while equipping quality teams with automated documentation and testing. Ketryx also automatically updates traceability and authorizes companies to use it as controls for change management to ensure they are following their PCCP. Our team empowers manufacturers to use the tools that are used by software professionals today to develop and update software.
FDA Predetermined Change Control Plan (PCCP) Template
Ketryx has built an in-depth PCCP template for manufacturers and companies looking to produce an FDA-compliant PCCP. This template explains the step by step instructions and procedures for each of the three components of the PCCP (Description of Modifications, Modification Protocol, Impact Assessment) along with an example product. It is designed for companies to easily replace text with their company specific information.
