Unusual corrective Action for Lack of Process Validation

In a recent Warning Letter, the FDA criticised the lack of process validation. What measures is the FDA requiring in this case and how did the company respond?

As there is no specific section about process validation in 21 CFR 211 (cGMP), the FDA cites 21 CFR 211.100 (a) here: 'Your firm failed to establish adequate 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.'

This concerns a topical product for pain relief for which process validation is completely lacking. Referring to its process validation guidance, the FDA points out that a process must be validated before the resulting product is distributed. This encompasses the entire process validation lifecycle.

Consequently, the FDA therefore requires a plan to ensure that there is continuous management oversight throughout the entire manufacturing cycle. Furthermore, the authority requires to see a data-driven and scientifically sound programme that identifies process variations and ensures that manufacturing operations (including packaging) comply with the relevant parameters and quality standards, and that process performance and product quality are continuously monitored. This includes the qualification of equipment, as well as ensuring the quality of raw materials.

In short: the FDA wants to see a programme for facility and equipment qualification and process validation.

The response from the company concerned is somewhat unusual: it is discontinuing the sale of the relevant products.

Conclusion: Facility and equipment qualification and process validation are essential elements of a quality management system.

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