POST-APPROVAL CHANGE MANAGEMENT PROTOCOL (PACMP)

POST-APPROVAL CHANGE MANAGEMENT PROTOCOL (PACMP)

A PACMP is a regulatory tool that provides predictability and transparency in terms of the requirements and studies needed to implement a change
• Provides an opportunity for lower reporting category when implementing changes
• Chapter Sections
– Definition
– Application – Step 1 & Step 2
– Elements
– Modification
– Types

PACMP tools that allow continued opportunities for streamlined change implementation
• Highly aligned with FDA draft guidance on Comparability Protocols
• Can be included with the original application, or with a post-approval supplement.

Why are the PACM Protocols so important?

ICH Q12 contains five very useful instruments. The main gain? They allow for agile lifecycle management. But they also have a positive impact on the industry and regulatory oversight practices such as:

  • Categorizing changes.
  • Producing protocols to manage each group of changes (PACMPs).
  • Establishing the basis of quality and regulatory commitments for manufacturing conditions.
  • Having a risk-based understanding and definition of the criticality of changes (“do & tell”, “tell & do”);
  • Having modern pharmaceutical quality systems at the core of the lifecycle management process to enable continuous improvement and an agile, compliant, robust management of pharmaceutical operations.

Therefore, part of the guideline is about tools that allow continued opportunities for streamlined change implementation. The tool we want to focus on is the Post-Approval Change Management Protocol (PACMP).

So, what is the point of PACMP? Well, PACMP is a tool that gives you a framework to implement changes in your already approved manufacturing process.

It describes:

  • Implementation of changes;
  • Preparation and Verification of changes;
  • Reporting category in line with the regional regulations and guidance.

Benefits
• Prospective agreement between applicant and regulator on:
– Change to be implemented
– Studies and acceptance criteria
– Implementation reporting category
• Allows for predictable change approaches that reduce ambiguity surrounding the implementation.
• Allows for shorter review clocks for change implementation, when appropriate.

Steps
Step 1
• Submission of a written protocol including:
– Description of the proposed change(s) with rationale(s)
– risk management activities
– proposed studies and acceptance criteria to assess the impact of the change(s)
– other conditions to be met
– the proposed reporting category
– any other supportive information

• Approved by the regulator in advance of execution of the protocol

Step 2
• Carry out tests and studies outlined in the protocol
– If results/data generated to meet the acceptance criteria and any other conditions
• submit this information to the regulatory authority according to the category in the approved protocol
– If results/data generated do not meet the acceptance criteria and any other conditions
• reduced reporting category is no longer valid
• default to existing regional regulation or guidance regarding change implementation
• Depending on the reporting category, approval by the regulatory authority may or may not be required prior to implementation of the change.

Elements

ICH Q12
• Description and rationale for the change
• Supporting information and analysis
• Specific tests, studies, analytical procedures, and acceptance criteria
• Discussion regarding the suitability of the approved control strategy
• Any other conditions to be met (e.g. selected PPQ activities)
• Proposed reporting category for step 2
• Confirmation that ongoing verification will be performed under the PQS.

FDA draft guidance
• Overall summary
• Description and rationale for the change
• Supporting information and analysis
• Specific tests, studies, analytical procedures, and acceptance criteria
• Proposed reporting category for step 2
• Other information (single or multi-use protocol)

Types
• One or more change(s) to a single product
• One or more changes to be implemented across multiple products
– E.g., change in stopper across multiple products that use the same container closure system
• One or more changes to be implemented across multiple products and at multiple sites
– E.g., change in analytical method across multiple sites, change in manufacturing site(s) across multiple products.

Modifications
• After approval of step 1, modifications made to the PACMP may require a supplement depending on the impact on the ability to assess product quality under the change
– Replacement or revision of protocol elements that result in the same or increased rigor is generally a lower impact:
• Tightened acceptance criteria
• Changes to comply with compendial requirements
– Modifications that significantly alter protocol content are generally higher impact:
• Adding additional applications to a broad protocol
• Changes to studies, methods, etc.

Expectations
• No change in a PACMP should introduce additional risks to safety, efficacy, or product quality
– PACMP is generally not suitable for quality changes that require supporting safety or efficacy data
• Periodic re-evaluation and confirmation of validity prior to execution or implementation
– MAH should follow existing guidance for change notification if an increased level of risk associated with the change is observed

• Appropriate defaulting to regional reporting requirements if:
– Risk of implementing the change has increased
– Failure to meet acceptance criteria
• Changes are designed, implemented, and monitored under an effective PQS
– PQS expectations
– Change management principles

Product Lifecycle Management Document (PLCM)

Serves as a central repository of key elements to provide transparency and facilitate:
– Strategic approaches to lifecycle management
– Lifecycle regulatory assessment and inspection

Maintenance
– The updated list should be submitted in post-approval submissions for CMC changes
– ECs should be updated based on knowledge gained during the lifecycle

Conclusion
• Broad alignment in ICH regions on the value of this tool to implement ICH Q12
• Up front alignment allows for:
– Predictable change implementation
– Better global product lifecycle management
– Enhanced transparency between regulator and MAH regarding the approach to risk assessment and control

 

 

 

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