These guidelines do not constitute additional requirements in the area of good manufacturing practices (GMP). The purpose of this Annex is to explain and promote the concept of validation, and to assist in establishing priorities and selecting approaches when a validation programme is being developed. Since the WHO guide on GMP (1) is applicable essentially to the manufacture of pharmaceutical dosage forms, this text is also concerned with the production of such finished forms. However, the general principles of process validation outlined here are relevant mainly to the manufacture of active ingredients. While the emphasis is on the production processes, many recommendations are also valid for supporting operations, such as cleaning. Analytical validation is not discussed here1. Further advice is given in "Validation of analytical procedures used in the examination of pharmaceutical materials" (2).
1 Analytical validation seeks to demonstrate that the analytical methods yield results which permit an objective evaluation of the quality of the pharmaceutical product as specified. The person responsible for the quality control laboratory should ensure that test methods are validated. The analytical devices used for these tests should be qualified and the measuring instruments used for the qualification should be calibrated. Each new test procedure should be validated.
The guide on GMP for pharmaceutical products (section 5) (7, page 27) requires the validation of critical processes as well as of changes in the manufacturing process which may affect product quality. Experience shows that few manufacturing processes do not contain steps which are "critical" that may cause variations in final product quality. A prudent manufacturer would therefore normally validate all production processes and supporting activities, including cleaning operations. The term "critical process" in this context indicates a process, operation or step that requires particularly close attention, e.g. sterilization, where the effect on product quality is crucial. It may be noted that certain GMP guides, e.g. that of the European Community (3), do not distinguish between critical and non-critical processes from the point of view of validation.