10 TonyTong Presentation CMC China June2010 Final.ppt

Quality by Design Approach to Formulation and Process DevelopmentCase Studies for NDA and ANDA Filings  Wei-Qin (Tony) Tong, Ph.D. Teva Pharmaceuticals USA TONYTONG@OPTONLINE.NET AAPS/CPA CMC Workshop June 28-29, 2010 What is Pharmaceutical Quality by Design (QbD)? Design and develop formulations and manufacturing processes to ensure pre-defined product quality Understand and control formulation and manufacturing process variables affecting the quality of a drug product Current CMC Review: Issues Quality by end product testing Little or no scrutiny on product and process design Product specifications Little or no mechanistic understanding “Overly conservative and often irrelevant specifications” Does not adjust review to the level of scientific understanding Quality by End Product Testing Quality by End Product Testing vs. Quality by Design Critical Steps of Quality by Design (QbD) Approach Define Target Product Profile (TPP) Solid Dosage Form Development Design Space Concept Design Space The multidimensional combination and interaction of input variables (e.g. material attributes) and process parameters that have been demonstrated to provide assurance of quality Design Space: Impact of Scale Design Space: Impact of IVIVC How Do You Judge Quality?- Critical Quality Attribute In vitro performance tests Assay Uniformity Purity Dissolution In Vivo performance tests PK/PD Clinical/Therapeutical effects Specs with clinical relevance Critical Material Attributes and Process Variables Critical Material Attributes and Process Variables (Continued) Process Development by QbD What is Process Validation? Process validation is defined by the FDA’s new guideline as the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products. Two key components: Understanding your process Ensuring it remains in a state of control Valida