Process Validation Deficiencies from the FDA's Perspective - Statistics for Fiscal Year 2021

Recommendation

4/5 October 2022
Heidelberg, Germany

Process Validation in the light of the revised Annex 15 and FDA Requirements

In the News on FDA Warning Letter Statistics regarding the fiscal year 2021 (October 2020 - September 2021) you could read that process validation deficiencies are on place 5. But what deficiencies did the FDA find in process validation?

In total, seven companies were criticised by the FDA in a Warning Letter about process validation deficiencies in fiscal year 2021. In these letters, the FDA refers to 21 CFR 211.100 (Subpart F- Production and Process Controls, written procedures; deviations).

Five of the seven companies had no process validation, and for two companies the PPQ batches failed. Interestingly, missing or insufficient equipment qualification was also criticised three times.

In response to their Warning Letter, the FDA requested almost always  

• a description of the validation programme, with references to the PPQ batches and the "Continued Process Verification", especially with regard to intra- and interbatch variability
• the submission of validation plans and reports
• SOPs related to process validation (and equipment qualification, were also criticised)
• a risk assessment if there are still products from the non-validated processes on the US-American market)
• a timetable for addressing the deficiencies

An concurrent validation, as a "quick fix" was not accepted by the FDA. Furthermore, the FDA Guidance "Process Validation: General Principles and Practices" is almost always cited as the basis for process validation and it is pointed out that a permanent "state of control" is required.