Validation process manufacturing

From the point in the process where full GMP compliance begins, the excipient should be produced in qualified equipment using a validated manufacturing process and testing should be done using validated methods. Where production equipment is not dedicated, validated cleaning methods are also needed. Full GMP compliance is required no later than the final excipient purification step or the manufacturing step where the excipient molecule has been synthesized, whichever occurs later in the process. 

A validated manufacturing process is one which has been proved to do what it purports or is represented to do. The proof of validation is obtained through the collection and evaluation of data, preferably, beginning from the process development phase and continuing through the production phase. Validation necessarily includes process qualification (the qualification of materials, equipment, systems, buildings, personnel), but it also includes the control on the entire process for repeated batches or runs. 

Since it is essential that only valid manufacturing processes be used, it is increasingly expected that data should be submitted in the application for marketing authorization demonstrating the validity of a given process.. .. ... 

Whereas it is accepted that validation data on the first production scale batches may not be available at the time of submission, it is considered essential that valid manufacturing processes are used and the data submitted in the application verify the validity of the process. Where production scale data are not available at time of submission, validation can be conducted in two steps a thorough characterization of the critical process parameters at pilot scale (presented in the dossier), followed by a formal validation program on production scale for which a protocol is included in the dossier. 

Then, how can sterility of batches of supposedly sterile products be confirmed by those functions within companies that are held responsible for product release The answer is in the use of validated manufacturing processes based on sound scientific evidence that each product unit is most probably sterile. 

Tlie development of validated manufacturing processes is a prerequisite for pharmaceutical application of the newer biotechnologicals, such as DNA for plasmid-based genes in vaccines and gene therapy. Using bioprocess-design information it is possible to create efficient and consistent processes for these materials. Key issues are the required piu ity, the sensitivity of the chromosomal DNA and larger plasmids to hydrodynamic forces, and the impact of the various characteristics of plasmids on the recovery and purification of DNA for pharmaceutical purposes. " " ... 

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