April 2015 CMC Special Report

Both the United States and the European Union offer guidance on a life-cycle approach to process validation. This goes beyond the traditional three to five lots run at the center point of proposed ranges for operating parameters. New approaches leverage product design and process development information. They facilitate adapting the QbD paradigm to allow for a science- and risk-based selection of critical process parameters, key process indicators, and appropriate specification criteria. The number of runs for process performance qualification (PPQ) must be determined using a risk-based understanding and control of process variability. This approach allows for more comprehensive use of multiple data sources to strengthen process understanding. Once process performance qualification has been executed, a stage of continued process verification begins for ensuring that a qualified control strategy is sufficient and that the process remains in a state of control. Following an appropriate time frame, process v...

The 15th WCBP CMC Strategy Forum, “Raw Material Control Strategies for Bioprocesses,” met on Sunday, 11 January 2009 in San Francisco, CA. This forum considered the design and implementation of control strategies for complex raw materials used in bioprocessing. Discussion focused on key approaches and application of risk assessment tools that can be used to identify and assist in mitigating potential safety and efficacy concerns that can affect the quality of biological products. Two Sessions To fully explore the topic, the forum first focused on recognizing and assessing potential risks associated with raw materials (RMs) and then applied those rationales to actual case studies with audience participation. The morning session began with an introduction to the topic followed by five presentations. Areas of discussion included how expectations for raw material control are evolving within changing regulatory and business paradigms including quality by design (QbD), counterfeiting, complex supply chains, and...

Multiproduct facilities are increasingly integral to corporate biologics network and supply chain strategies. Manufacturing capacity strategies ensuring appropriate facility design and procedural controls to manage the risks of producing multiple products are critical to the successful deployment of commercial and clinical supply plans. A Chemistry, Manufacturing, and Controls (CMC) Strategy forum was held in Bethesda, MD, in August 2011 to highlight various challenges, risks, and control strategies associated with multiproduct facilities. Multiproduct strategies for the manufacture of a variety of product types at different life-cycle stages and potentially using different host cells were presented with case studies. Experts from both industry and global health authorities discussed facility design considerations as well as procedural controls such as cleaning validation and product testing. The importance of quality risk management (QRM) to multiproduct operations and controls was also discussed using p...