(209a) QbD and the Transition From Wyeth to Pfizer for API Small-Molecule Development and Manufacture

Quality by Design (QbD) is playing a major role in the development and manufacturing arenas of the Pharma industry. Process Understanding, the central component of QbD, is augmented by applying essential tools such as Multivariate Analysis (MVA), Design of Experiments (DOE) and Process Analytical Technology (PAT). While QbD in the Pharma industry is formally applied to the safety and efficacy of the product for the patient, the antecedent drug substance is a critical component of this process. A robust and well understood process for the production of drug substance evolves from a risk-based approach for defining critical quality attributes and establishing the design space for the API, key intermediates and starting materials to assure consistent quality. Process understanding begins during development, so it is imperative that an effective system is in place to impart QbD that is effectively bridged to manufacturing and product lifecycle within an environment of co-development. In addition to a sound, science-based approach, QbD is an important component of good business practice leading to fewer surprises during manufacturing, thereby affording good supply assurance. The application of QbD in API small molecule development and manufacturing during the transition from legacy Wyeth to Pfizer will be presented within the framework of the different models used at each company. Brief case studies will be utilized to demonstrate application of QbD for API's for a late development drug candidate and a marketed product.