Qualification and validation belong to the most significant fields in the pharmaceutical industry. There is almost no authority inspection without controls of these fields. The regulatory guidelines only give general description, e.g. Annex 15 of the EU GMP Guide, FDA Process Validation Guidance. Some regulation indications are partly given by the industry (e.g. ISPE-Baselines, GAMP).
What is important during an inspection? Only little information is available.
The PIC/S document PI 006 is used for the training of inspectors, the FDA has a "Validation Documentation Inspection Guide" which has never been officially recognized ("Lost Guide"), though. In the FDA "Guide to Inspection of" documents (e.g. on water systems or on quality controls) some theme-related qualification and validation aspects are also described.
The EFG 10 group of experts (qualification/validation) - belonging to the Central Authority of the Länder for Health Protection with regard to Medicinal Products and Medicinal Devices (ZLG), Bonn/Germany - has published an Aide Memoire on inspections for the German inspectors. This document was revised last year and now provides an updated presentation of the qualification/validation topics. This Aide Memoire contains much information classified in 9 chapters/ 52 pages. Beside definitions and abbreviations (also regarding statistical sizes), the document describes what inspectors have to consider with regard to:
The respective responsibilities, requirements on documentation as well as the risk analysis question are also presented in the document which provides helpful details about reference values, for example regarding the microbiological air quality for the manufacture of solid products. Criteria for exclusion for the applicability of a retrospective qualification are mentioned. The Chapter about cleaning validation defines Hygienic Design as a fundamental requirement for cleanability and describes design aspects of CIP-equipment. Even the riboflavin test is mentioned.
The Process Validation chapter also underlines the relevance of the Aide Memoire: process understanding and knowledge are focused on (like in the new FDA Process Validation Guidance). Consequently, 3 validation cycles are not sufficient anymore. Subchapter include information about PAT and the statistical process control. Modern aspects on re-validation also strongly remind of the stage 3 "continuous process verification" required in the new FDA Process Validation Guidance. Minimal observation on methods and processes transfer in the case of a risk analysis also shows the relevance of the Aide Memoire (Chapter 8).
Conclusion: this Aide Memoire on Qualification/Validation is a very complete and helpful tool to prepare for an inspection regarding on these topics.
From ECA's perspective this document is quite important and will therefore be exclusively distributed (in English language) to the participants of the 4th European GMP Conference, which will take place in Heidelberg, Germany, on 19/20 May 2011.
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)