Process Validation

In a recentlyposted warning letter to a Chinese drug manufacturer the FDA identified a specific violation citing the Jan 2011 FDA Guidance to process validation.

Your firm failed to establish written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).

 You have not validated the processes used to manufacture your drug products, you did not define or identify critical process parameters, and you lack an ongoing program for monitoring process controls to ensure stable manufacturing operations and consistent drug quality.

 See FDA’s guidance document Process Validation: General Principles and Practices for general principles and elements of process validation at

 This is interesting as the warning letter identifies the lack of critical process parameters which are necessary to ensure the process remains in a state of control and are discussed in Pharmaceutical Development ICH Q8(R2) section 2.3:

The manufacturing process development program or process improvement program should identify any critical process parameters that should be monitored or controlled (e.g., granulation end point) to ensure that the product is of the desired quality. 

 Section 2.5 Control strategy:

These controls should be based on product, formulation and process understanding and should include, at a minimum, control of the critical process parameters1 and material attributes.  

 The FDA Guide to Process Validation discussed identifying these parameters in Stage 1 process design, and then testing them as part of Stage 2.  Of interest is the final part of the citation – failure to have an ongoing program for monitoring process controls – this is identified in Stage 3 of the process validation guidance and is necessary to demonstrate that the manufacturing process remains in a state of control.