Pharmaceuticals process validation development 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. 

However, it cannot be assumed that all processes in the pharmaceutical industry worldwide have been properly validated at the development stage. Consequently, validation is discussed here in a broader context as an activity which is initiated in development and is continued until the stage of full-scale production is reached, in fact it is in the course of development that critical processes, steps or unit operations are identified. 1... 

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. 

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. 

Although the requirements of validation have been clearly documented by regulatory authorities, the approach to validation is varied and open to interpretation. The following approach will focus on the International Conference on Harmonization (ICH) guidelines. Also, because validation requirements differ during the development process of pharmaceuticals, this chapter will emphasize requirements for later stages of development and for methods used to evaluate marketed products. 

---