Making Post-Approval Changes can be a challenge. You have different timelines, different submission requirements and trouble optimising your processes. Because of that, this makes the knowledge of creating a post-approval change management (PACM) protocol all the more important.

And that’s what this blog post is all about! In it, we’ll talk about the ICH Q12 and how it supports the creation of a PACMP. And then we’ll go through the steps of creating one!

Where did the PACM Protocol come from?

Some of the guidelines had already introduced Quality by Design (QbD) concepts to product development and manufacturing. We’re talking, of course, of the ICH Q8, Q9, Q10 and Q11!

However, they weren’t all too clear on the topic of Product Lifecycle Management. And because of that, in 2017, the ICH published a new guideline with the impressive name of “Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management“: the ICH Q12!

So, this guideline has a different focus from the others. Starting with biologics, going through API’s or even drug-device combinations, it addresses Established Conditions (ECs), Product Lifecycle Management (PLM), Pharmaceutical Quality System (PQS) and the topic of this blog: Post-Approval Change Management Protocol!

So, let’s focus on the world of post-approval changes for products already in the market.

Why are the PACM Protocols so important?

ICH Q12 contains 5 very useful instruments. The main gain? They allow for agile lifecycle management. But they also have a positive impact in 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.

The benefits of having an PACM Protocols.

Having an optimised and streamlined PACM Protocol has a lot of benefits. Benefits both for your company and for your product manufacturing. Benefits such as:

  • Predictability and transparency of the requirements and studies needed to implement a change;
  • A lower reporting category when implementing changes with shorter review clocks;
  • Prospective agreements between you and the regulator.

However, submitting a PACM Protocol can be as tough as it sounds. Let’s have a look on what you need to consider for change implementation.

Let’s apply a PACM Protocol. How hard can it be?

All right, time for the challenge of applying a Post-Approval Change Management Protocol!

You need to focus on two steps to guarantee that things will work themselves out.

Step 1. Submit a written protocol that needs to include the following points:

  • A description of the changes you’re going to propose and their rationale;
  • The risk management activities;
  • A studies proposal and the acceptance criteria to assess the changes impact;
  • Other studies that need to be met.

Before executing this protocol, the regulatory authority will have to review it and approve it.  If they do approve them, congratulations! You’re ready to take on the next step.

Step 2. Carry out test and studies defined in the protocol.

So, you have defined your criteria, and they have been approved. You go ahead and perform your tests. But like with any tests, there are two possible outcomes:

  • You meet the acceptance criteria and any other conditions. That is the best outcome possible. Now you must submit them to the regulatory authority, according to the category approved in step 1.
  • You fail to meet acceptance criteria or any other conditions: That means that the change cannot be implemented using your approach. You need to follow the existing regulation or guidance.

Please keep in mind that, if you make significant changes that were not anticipated in the step 1, you can’t implement them as part of step 2. Why? Because no change outlined in a PACMP should introduce any additional risk to patient safety, product quality or efficiency.

Distinct types of PACM protocols.

If you came this far, it should be clear by now the context of the ICH Q12 guideline, how to submit a post-approval change and even the benefits of having an optimised protocol can bring to your products manufacturing.

But where can you apply a PACMP? Plenty of places! A PACMP can be applied in:

  • A sole product;
  • Across multiple products;
  • Across multiple products and at multiple sites.

We suggest you have a look at ICH Q12 guidelines to learn in better detail how can you implement PACMPs at each of the points that we presented.

We can support the creation of your PACM Protocol.

Having a Post Approval Change Protocol implies a careful risk analysis and a full understanding of the different risk assessments. That will assure that safety, quality, and efficiency are never compromised.

Our team is highly specialized in optimising Quality Risk Management Processes. We make use of decades of experience and our proprietary Risk Management software to ensure that your risk activities are align with FDA and ICH guidelines.

If you want to know more about it, please contact us.

Related Topics

Is Post-Approval Changes a topic of interest to you? Then you shouldn’t miss our blog posts about Compatibility for Post Approval-Changes.