Change Control and (Re)Validation - The FDA Perspective

The topic of revalidation is rarely mentioned in the regulations. Ongoing/continued process verification has replaced regular revalidation (with exceptions in the sterile area). But what can happen after a change control? Read the FDA's opinion below.

In a Warning Letter, the FDA describes what it expects in the event of a change in the process. What is it about?

The lack of sufficient validation was criticised. In addition, as a result of customer complaints regarding the viscosity of the product, the company changed two ingredients without change control. The new process was not (re)validated. The FDA does not explicitly refer to revalidation here, but only validation. With reference to its process validation guideline, the FDA then explains what it understands by process validation.

The company's response that it had initiated a structured approach to process validation was not sufficient for the FDA. The authority requires the demonstration of appropriate process validation procedures and plans. Furthermore, the FDA would like to see a timeline for the implementation of CAPA measures or risk assessments on products that have been released without appropriate validation or testing.

The FDA further requires

• A plan to ensure that there is continuous monitoring throughout the manufacturing lifecycle of all medicinal products. 
• A data-driven and science-based programme to identify process variability and ensure that the necessary parameters and product quality are maintained. 
• A summary of the validation programme to ensure that a state of control is maintained throughout the product life cycle, together with the associated procedures. 
• A description of the Process Performance Qualification (PPQ) programme 
• A description of the monitoring activities to assess intra-batch and inter-batch variability to ensure state of control 
• A schedule for the implementation of the PPQ for each of the marketed medicinal products 
• A detailed programme for the development, validation, maintenance, control and monitoring of each manufacturing process, with regard to intra- and inter-batch variability to ensure a state of control 
• A programme for the qualification of plant and equipment.

Conclusion: Process changes can trigger an event-related (re)validation, whereby the FDA does not use the term revalidation, but only refers to validation.

You can find the entire Warning Letter on the FDA website.