7 Process Validation
Detailed regulations on the aims and execution of process validation on a Euro- pean level can be found in the EU Guidelines to Good Manufacturing Practice for Medicinal Products (see chapter C.4). According to section 5.22, when any new manufacturing formula or processing method is introduced, steps should be taken to demonstrate its suitability for routine operation. It should be demon- strated that the defined process using the established materials and equipment will consistently produce a product of the required quality.
In the USA, validation has been a legal requirement for more than 30 years. References in the GMP regulations from Section 211.100 and 211.110 are the his- torical basis for what today is commonly referred to by FDA as the foundation of validation.
“There shall be written procedures for production and process control designed to assure that drug products have the identity, strength, quality and purity they purport or are represented to possess … these written procedures, including any changes, shall be drafted, reviewed, and approved by the appropriate organizational units and reviewed and approved by the quality control unit”. “Designed to assure” can be interpreted as the beginning of the concept for “Val- idation”.
The process for executing validation on a European level is described in Annex 15 of the EU Guidelines to Good Manufacturing Practice for Medicinal Products (see chapter C.6.15 Annex 15 Qualification and Validation). As Annex 15 contains only the principles of qualification and validation, the PIC/S document PI 006 (see chapter F.1 PIC/S PI 006-3: Recommendations on Validation Master Plan Installation and Operational Qualification Non-Sterile Process Validation Cleaning Validation) can assist with the interpretation and the implementation. This docu- ment applies primarily to inspectorates of the PIC/S member states, for whom it is intended as instruction for preparing an inspection, and as an advanced training aid for qualification/validation. As, for PIC/S purposes, this reflects the latest scien- tific and technological developments, valuable information regarding the imple- mentation of the specifications in Annex 15 may also be found here for the indus- try.
The USA has similar documents, which can be referred to for guidance when implementing validation activities and practices, especially the Guidance for Industry on Process Validation, which has been revised and published in January 2011 (see chapter D.2). Some more Guidance documents and Inspection Guides are included in Chapter D of this manual (chapter D USA: CFR and FDA Guidelines). The Inspection Guides and Guidances issued by FDA provide greater detail in acceptable validation practices than can be found in regulations issued by FDA. It is also suggested that the FDA homepage (www.fda.gov) be periodi- cally searched for new information being considered (draft) or issued by the FDA on relevant subjects. Since the United States, the EU, and Japan all participate in
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