Quality by Design: A New Paradigm for the Development and Commercialization of Biopharmaceuticals

The paradigm for biopharmaceutical development and commercialization has been dramatically impacted by the advent of Quality by Design approaches that have been driven by the regulatory authorities and encapsulated in recent FDA, EMEA, and ICH guidelines. The traditional approach, in which the process provides for the characteristics of the product (a paradigm in which “the process is the product”), is being replaced by development programs that pre-define the desirable product quality attributes and then develop the process to reproducibly meet those requirements. This approach, used in many industries to build the quality into the product, relies heavily on understanding how the characteristics of the product are impacted by the manufacturing process, as well as on the use of risk assessment methodologies to focus the process and product control strategies on the attributes of the product that impact its quality. This strategy is replacing the traditional approach, in which a large battery of analytical tests- “all of the usual suspects”- are tracked by in-process and/or release (specification) tests without regard to whether or not variations in product attributes impact the safety or efficacy of the product. The structural and functional complexity of biological drugs will be presented, along with the analytical approaches that are used to track quality attributes of biopharmaceuticals. The application of Quality by Design principles to the development of monoclonal antibodies (the major class of licensed biopharmaceuticals) will be emphasized. The use of powerful modern analytical tools to determine the physiological relevance of protein quality attributes will be presented to demonstrate how product knowledge informs the process control strategy and product specifications. The importance of protein immunogenicity, and the ways in immunogenicity risks can be mitigated, will also be discussed. The advantages of Quality-by-Design approaches in process, formulation, and analytical development, and how the Quality by Design approach enables product commercialization, will be presented, along with case studies to illustrate key concepts of the Quality-by-Design approach. In summary, this seminar will provide the attendee with an understanding of how the Quality by Design approach has altered the way in which modern biopharmaceuticals are developed, manufactured, and licensed by the regulatory authorities.