Process Validation and Implementation

Process validation, which is part of good manufacturing practices (cGMPs), is necessary for approval to market drugs. The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and its counterparts have issued a number of guidances to assist in the development and approval of drug processes. Process validation begins with laboratory optimization, before a process is implemented on scale. Understanding the process is necessary to control the quality of the product; quality cannot be tested into a product. The critical process parameters (CPPs) must be suitably controlled to produce material that has the desired critical quality attributes (CQAs). The conditions that are demonstrated to generate acceptable material are known as the proven acceptable range (PAR), and the preferred operating range that lies within the PAR is the normal operating range (NOR). Product generated outside the PAR may not have acceptable CQAs. Guidelines are discussed for validation efforts before, during, and after manufacturing introduction. Approaches for preparing a batch record (aka log sheet) are included. Considerations for managing outsourcing through contract research organizations (CRO) and contract manufacturing organizations (CMO) are discussed, along with due diligence.