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Biopharmaceuticals are an important part of the present day healthcare industry. Research, early stage development, scale-up, technology transfer, and commercial manufacturing are important phases of any drug product life cycle. Under ideal conditions, processes can be scaled up from lab to manufacturing scale based on the theoretical considerations. But, there are various non-process related issues which can impact the process performance and need to be considered for successful scale-up and technology transfer to manufacturing. This thesis presents three case studies which focus on the approaches for overcoming technical challenges encountered during scale-up, technology transfer and production of therapeutic enzymes at large scale. Case study 1 describes the strategies and process development activities associated with technology transfer of a clarification and capture ultrafiltration and diafiltration (UFDF) process from a pilot scale into a manufacturing plant that utilizes single use disposables technology. Case study 2 discusses the studies performed to develop column packing and qualification methods to address the challenges associated with platform approach and manufacturing at multiple sites. Case study 3 discusses the unanticipated changes required for methods to pack highly compressible chromatography media, post technology transfer to manufacturing scale, to minimize the risk of process failure.
Advisor: Delmar C Timm