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A Predetermined Change Control Plan (PCCP) is a regulatory framework that manages how modifications are made to medical devices and software that use artificial intelligence (AI) and machine learning (ML). PCCPs are commonly used in the medical device, pharmaceutical, and biotechnology industries. The documents submitted by manufacturers during regulatory approval detail any modifications to the device or software and how those modifications will be assessed. Examples of potential changes include algorithm updates and performance enhancements. The PCCP must include how these changes are validated, tested, and implemented to maintain safety and compliance. PCCPs also include:
The benefit of PCCPs is that they allow manufacturers to plan and validate future changes to a relevant product or process without resubmitting a new marketing application to the U.S. Food and Drug Administration (FDA). This approach is key in life sciences, as AI and ML-backed devices often evolve at a rapid pace. PCCPs allow for important regulatory oversight and product innovation.
PCCPs also drive agility because life sciences manufacturers can define and validate potential scenarios before moving forward with modifications. PCCPs are part of an ecosystem of global quality and regulatory frameworks. These include:
ISO 13485 (outlining quality management systems for medical devices).
The FDA Quality Management System Regulation (QMSR) (regulating design control, risk management, and post-market surveillance for medical devices and software as medical devices).
ICH Q10 (a pharmaceutical quality system model for product lifecycle quality).
The frameworks are designed to integrate continuous improvement, product innovation, and quality, particularly for AI-driven devices and products. In the past, regulatory control relied heavily on static submissions. These submissions often required full premarket approval or additional submissions for even minor modifications. They hindered the development of devices and software products leveraging emerging technology. As a result, agencies worked to align regulatory requirements with the pace of these cutting-edge products. The PCCP framework is an example of these efforts to create a more proactive, adaptive governance model.
In Europe, the European Medicines Agency (EMA) and the European Commission have taken a similar approach with the Medical Device Regulation (MDR) and the In Vitro Diagnostic Regulation (IVDR). These regulations emphasize transparency, clinical evidence, and preplanned modifications. Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) has published its own framework, the SaMD Change Management Plan, for preapproved postmarket changes. Through this framework, manufacturers outline planned modifications in advance. All of these frameworks are indicative of a larger shift to align innovation, safety, compliance, and technological advancements.
For a PCCP to be accepted by regulators, the document must demonstrate that all modifications can be made safely and effectively within the predefined boundaries. Predefined boundaries refer to specific permissible changes that can be implemented without additional regulatory approval. These boundaries include the type of changes, performance limits, risk thresholds, and operational conditions. Furthermore, PCCPs must align with the ISO 13485 and the 21 CFR Part 820 (QSR).
Key elements of a PCCP include:
Description of changes: Clearly outlined specific modifications (e.g., systems, components, or processes) and the scope, such as an affected device function.
Predefined boundaries: Limits for changes and operational conditions (e.g., patient population).
Risk assessment: A risk analysis consistent with ISO 14971 risk management principles to identify potential hazards that the proposed modifications may cause. Document mitigation strategy to address these hazards and risks.
Verification and validation protocols: Include test methods, acceptance criteria, and performance metrics used to ensure changes meet specifications around quality and safety.
Change protocol and documentation: Outline steps for design updates, manufacturing adjustments, or analytical changes and ensure all are recorded in an electronic change control system.
Implementation plan: Detail relevant procedures for executing changes, such as timelines and responsible parties. Include updates to labeling, user training, and documentation. Note responsibility for approval, execution, and review across quality, regulatory, and engineering teams.
Postmarket surveillance: Plan for monitoring real-world performance and meet requirements for ISO 13485 and QSR compliance.
Reporting mechanism: Include a reporting mechanism to regulators, meaning how the manufacturer plans to notify regulators once the modification occurs.
The step-by-step process of creating a PCCP includes drafting the document and defining verification methods. After internal review, the document is then submitted for regulatory review. Once the document is approved, the modifications can be implemented. Be sure to document outcomes and report to the FDA as required.
PCCPs allow medical device manufacturers to make important software updates and material changes without repeated regulatory approvals. For example, a medical device manufacturer can use a PCCP to predefine how they will retrain an AI algorithm as new datasets are made available for a diagnostic tool. This framework balances innovation with FDA and EU MDR compliance. PCCPs do not apply to major design changes, which would require a new regulatory submission.
PCCP for medical devices should include traceability between the proposed modifications, supporting data, and validation results. This means manufacturers must link the path from the proposed modification to the data supporting why the change is needed or justified to validate results that provide the change works without introducing new risks. Doing so allows regulators to verify that each modification is justified, tested, and documented in accordance with quality and safety requirements.
MasterControl’s connected quality management system (QMS) syncs PCCP activities with document control, training, and corrective action/preventive action (CAPA) records.
Similar to medical device manufacturers, pharmaceutical manufacturers can improve and adjust processes and analytical methods without the need for repeated regulatory submissions. This allows for continuous manufacturing, process analytical technology (PAT), and digital quality control initiatives. As an example, a pharmaceutical manufacturer can adjust a formulation mixing step as new available data. Or a company could adjust its tablet coating process to enhance stability. With a PCCP, these modifications can be made within the predefined boundaries.
The PCCP framework aligns with the principles of ICH Q12. The ICH Q12 is a global framework that helps pharmaceutical companies manage product and process changes across the lifecycle. Similarly, it does not require regulatory submissions for minor modifications.
PCCPs help drive continuous monitoring. They allow for process improvements in real-time within predefined boundaries. Pharmaceutical manufacturers can ensure innovation in their design while meeting patient safety and product quality requirements.
PCCPs help manage complex production environments found in biotechnology manufacturing environments. Examples include biologics, vaccines, and gene therapies. These environments rely on living cells and biological systems and demand strict control across all process parameters to maintain safety and consistency. As a result, any process change could have a significant impact on the quality and consistency of related products. With PCCPs, biotechnology manufacturers can plan for these process modifications in advance. The framework establishes clear boundaries, testing protocols, and validation methods.
For example, a biotech manufacturer could predefine plans to optimize cell culture temperature based on process analytics data as it becomes available. Or a company could use a PCCP to pre-approve parameter ranges for temperature adjustments during fermentation to improve yield. This framework drives process improvements and good manufacturing practice (GMP) compliance. It also ensures consistent performance and quality as processes and innovations evolve. Biotech manufacturers benefit from less regulatory burden and faster development timelines.
You can integrate PCCPs directly into a quality management system (QMS) to create a central view of approvals, documentation, and validation activities. Be sure to use automated workflows to track any proposed modifications. This will allow you to continuously monitor everything from initiation to implementation and maintain traceability as well as audit readiness. The end goal is to ensure every modification is documented, compliant, and aligns with the related regulatory requirements.
To demonstrate the effectiveness of your PCCP processes, monitor metrics such as approval turnaround time, deviation frequency, and post-change performance stability. These metrics will provide supporting evidence about whether your PCCP is leading to measurable efficiency and product quality. Consider means of validating that your process consistently delivers controlled, compliant innovation. You may track audit outcomes, any CAPA recurrences, and complaints around changes to do so.
PCCPs are to be reviewed annually or whenever you have new data, technology, or regulatory requirements. The following are triggers for revisions:
Updated guidance from agencies.
Repeated deviations.
Process changes outside predefined boundaries.
Regular reviews are essential to ensure all relevant plans are current and scientifically valid. They also make sure these plans align with organizational compliance frameworks.
Personnel involved in developing and executing PCCPs should receive targeted training. Topics include regulatory expectations, risk management principles, and digital change control workflows. You will also want to cover how PCCPs integrate into your QMS and the evidence expected by regulators. Train personnel on how to document, verify, and validate modifications within defined boundaries.