Pharmaceuticals process validation stages

The use of appropriate DOE can be an invaluable tool to optimize use of resources at all stages of product development, and to shorten the development time from for-mulation/process screening to optimization. When the formulation and manufacturing processes of a pharmaceutical product are designed and optimized by a scientific and systematic approach, the scale-up, technology transfer between manufacturing sites, and process validation can be more efficient because of the robustness of the formulation and manufacturing process. 

Before process validation can be started, manufacturing equipment and control instruments, as well as the formulation, must be qualified. The formulation of a pharmaceutical product should be studied in detail and qualified at the development stage, i.e., before the application for the marketing authorization is submitted. This involves preformulation studies, studies on the compatibility of active ingredients and excipients, and of final drug product and packaging material, stability studies, etc. 

When this definition of fitness for purpose is applied to toe pharmaceutical industry, it can be seen to fit well with toe concepts of quality. Personnel have to be shown to be fit for purpose for toe job they are employed to do (training, education and experience). Equipment needs to be demonstrated as fit for purpose based on qualification/validation, maintenance and calibration. Manufacturing processes are deemed fit for purpose based on in-process testing, process validation, etc. Process materials are shown to be fit for purpose based on testing appropriate to their intended use in toe process. This use will vary depending on toe stage of processing and whether it is a primary (chemical) process or a secondary (formulation) process. 

In summary, process capability studies start in the development laboratories and/or during product and process development, and continue in well-defined stages until the process is validated in the pilot plant and/or pharmaceutical production. 

It must be stressed that a good engineering and project process is the best basis for proper qualification and validation work. It is the current opinion on qualification in the pharmaceutical industry that the later steps in the qualification process need more time and attention than the earlier steps. This may be totally different in other industry branches they tend to spend more effort during the earlier stages to save time and money later on. 

Data mining of chemical databases is still at its very early stage. Nevertheless, as a result of the data explosion in pharmaceutical industry, it is expected that data mining techniques will play an increasingly important role in the drug discovery process. Future studies may include, for example, the definition of chemical space, the validation of various algorithms (206), and the representation of extremely large virtual databases (207). 

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