Working with the New 2011 Guidelines.

In January 2011, the FDA issued its newest guidance for Process Validation for industry and it is quite a departure from the previous guidance released in 1987. The old approach of developing products and hoping that testing would provide enough information to predict and control the process is no longer the order of the day. What does the new guidance contain and how does it differ from the 1987 version? Let’s compare the two approaches to see where the changes lie and why they are important.

Back in 1987, the FDA defined process validation as a process of establishing documented evidence, with a high degree of assurance, that a specific process would consistently produce a product meeting predetermined specifications and quality characteristics. At that time, the industry’s approach meant providing evidence from process development, from validating facilities, equipment, and cleaning, as well as process monitoring to support the process validation claim of having a stable and predictable process for manufacturing products. Proving quality through documentation and inspection has inherent deficiencies, however. Each part of the information pooled to make up the evidence for process stability constituted an operation that could be performed independently. Without the consistency of pulling together information from the entire process validation lifecycle in a concerted effort as a baseline for claims, the risk that key process variables could go unmonitored was liable to occur. And it often did. A case in point: how many times have we experienced failed acceptance criteria during the third run of a performance qualification or during a process validation run without immediately understanding why the failure occurred? In how many instances have we witnessed manufacturing runs slowly move out of specifications and finally exceed acceptance criteria so that we have to perform costly investigations to determine the cause of the issue?

The 2011 guidance provides a different approach to process validation, already revealed in the draft guidance introduced in 2008. This new approach caught the attention of the industry and spurred a huge response due to the drastic change from the 1987 guidance. More modern, the 2011 guidance aligns itself with many of the ideas in the FDA/International Conference on Harmonization (ICH) guidance for industry, Q8 (R2) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System. In essence, the FDA shifts its focus from proving quality through documentation and inspection to demonstrating it through sound scientific principles. Now, the FDA defines process validation as the collection and evaluation of data, from the process design stage to validation and throughout production. Scientific evidence is to be used to prove that the process is capable of delivering consistently manufactured quality products.