Best Practices for Post-Approval Change Management Protocols (PACMPs)

Sometimes, pharmaceutical companies need to perform changes to the formulation of a product, its manufacturing process, or controls (CMC) after approval. Thus, a Post-Approval Change Management Protocol (known as Comparability Protocol in the United States) must be developed to ensure a streamlined submission, a faster time to market, and a continuous supply of safe medicines to patients. This article lists some practices to design protocols that promote regulatory compliance while also helping to avoid delays.

Why assessing the reporting category can save time

An approved PACMP may allow downgrading the category of changes requested from a major variation to a lower tier. Beyond achieving a faster time to market, this can also ensure that products with high demand do not suffer supply interruptions. According to the European Medicines Agency, the category designated for reporting changes under a PACMP is at least one category lower than normal.

To back the selection of a reporting category, it is necessary to include a risk assessment of the changes, as well as a detailed comparability and stability studies data that proves that the product remains safe and as effective as before. 

Build a protocol based on the regulatory framework

Failure to meet regulatory requirements is one reason that causes delays while submitting changes. While drafting a PACMP, it is essential to confirm with regulators that the data and tests considered for submission support the change requested and satisfy the latest institutional guidelines. By minimizing ambiguity, companies can propose protocols that are compliant and execute changes in a predictable and safe manner.

The development of this strategy requires engaging regulators early in order to agree on the reporting category that the changes will require, as well as the supporting data needed to back them. This written protocol is the first step of two that the PACMP encompasses, and must describe:

• The proposed changes and their rationale

• Risk management activities

• Proposed studies

• Acceptance criteria to assess the impact of the changes.

• Other conditions to be met

• The proposed reporting category for the change.

• Other support information. 

  
  

Perform tests based on the written protocol

The second crucial part of a PACMP is the execution of the tests outlined in the written protocol. Adhering to this protocol requires that there is clear communication within the regulatory and laboratory teams, particularly if the tests are performed in different sites or if the team is split in different locations.

The goal of testing is to generate data that meets the protocol acceptance criteria. Once this is achieved, this data can be submitted to the regulators according to the defined category. Depending on the category selected, further approval may be required before continuing to implement changes.

It is very important to consider that significant changes cannot be added during the testing stage. However, small process modifications are allowed as long as they do not stray away from the technical principles of the protocol and they are thoroughly justified.

Build a PACMPs repository to reduce future workload

While some changes are a one-off, others may be recurring. Therefore, having a repository of PACMPs or developing a PACMPs template can save time while also improving operational agility. This is quite useful for companies operating across borders, and they have to coordinate international supply chains across multiple sites.

A well-designed repository contains recent and past PACMPs, which are properly tagged and categorised to ease finding information. Templates can also be included in this archive, especially if the same type of change will be requested repeatedly. These templates should include a document that defines the scope of action and category of changes that the template supports. In addition, the template should be reviewed periodically to verify that it remains compliant with the current regulatory expectations.

It is important to note that templates are meant to be tailored to the particular changes requested. Different modifications require different data and may need to comply with different regulatory requirements.

Support PACMPs by improving supply management

A PACMP can be a useful tool to maintain continuous production, scale operations, and even add new sites. Thus, it is advisable to design a supply management strategy that removes the internal obstacles (such as long approval cycles) that could slow down the implementation of a PACMP. 

Beyond streamlining manufacturing processes, supply management can also support a PACMP by taking ownership over crucial data such as site descriptions, equipment specs, and validation protocols. By doing this proactively, organisations can easily replicate changes across multiple sites while also remaining compliant.

In conclusion, PACMPs have both practical and regulatory implications for pharmaceutical companies. Beyond increasing the chances of approval, it can also help to align the company better to regulatory requirements, as well as facilitate the replication of changes to processes split across multiple sites.