Process validation guidelines

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Process validation guidelines

In 2011, FDA published an updated guidance document, Process Validation: General Principles and Practices, which replaced the previous 1987 version (2). The changes in the guidelines reflect an increased emphasis on a scientific, data-driven approach to process validation and a more holistic view of the product lifecycle, which includes the following stages:

Stage 1—Process Design
Stage 2—Process Qualification
Stage 3—Continued Process Verification.

The core of each stage is “the collection and evaluation of data…which establishes scientific evidence that a process is capable of consistently delivering quality products” (2). These guidelines are explicitly aligned with the risk-based approach outlined in International Council for Harmonization (ICH) Q8 (R2), Q9, and Q10 including quality by design (QbD).

Prior to this, process validation was generally considered a commercialization activity and typically involved running three batches to demonstrate that the process was reproducible and capable of delivering consistent product quality. The updated guidelines recommend the use of statistical techniques to demonstrate process capability and emphasize the importance of providing “sufficient statistical confidence of quality both within a batch and between batches” (2). It is well established that, for biologics, the process is the product; therefore, ensuring that the process is well characterized is essential for maintaining product quality.

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