In recent years biotech companies have been emphasizing the implementation and utilization of process analytical technology (PAT) in continuous bioprocessing. An overview of PAT concepts for biotech processes with emphasis on integrated continuous bioprocessing and production of monoclonal antibodies will be presented. Biotech processes consist of several unit operations, with each unit operation serving a defined purpose. For some of the product quality attributes, a certain level of redundancy in the process is expected. The need for appropriate control of each step and continuous evaluation of its performance is of great importance. The objective of commonly used unit operations in downstream processing of biotech products is to isolate the product of interest from the process stream that comes from the harvest unit operations and contains a variety of impurities. These impurities include product-related variants that might closely resemble the desired product and have an equivalent potency and safety profile. Spectroscopy is being proposed as an on-line PAT tool for continuous measurement of numerous critical quality attributes. In addition, real-time data collection will assist in the development of chemometric models used for predictive estimation of properties of a process and hence help in process analysis, optimization, monitoring, and control.
Dr. Edita Botonjic-Sehic joined Pall Corporation in late 2016 and is currently Global Process Analytical Technology (PAT) Manager. In this role, she is responsible for the strategic conceptualization and implementation of process analytical technology (PAT) for the continuous bioprocessing portfolio. She brings more than 14 years of experience in spectroscopy and chemometrics for PAT and advanced analytical techniques to advancing this new concept. Prior to joining Pall Life Sciences, Dr. Botonjic-Sehic was a member of the PAT team within GlaxoSmithKline’s program for API development, and she also led a PAT team at TEVA Pharmaceuticals for drug product manufacturing, and was a principal investigator and program manager on several government-funded (DHS, TSWG, CTTSO) projects at Morpho Detection (formerly GE Homeland Security), where she specifically worked on the development of systems for trace and bulk materials detection. Dr. Botonjic-Sehic completed her PhD in Analytical Chemistry at the University of Rhode Island after undergraduate studies at Assumption College in both chemistry and mathematics. She is a respected leader in her field and an accomplished author of numerous papers, and frequently delivers talks in the field of spectroscopy and chemometrics.
John M. Baust, PhD is the Founder, President, and Lead Scientist of CPSI Biotech. Dr. Baust has 15+ years’ experience in research & medical device development and is a co-inventor on over 40 patents. Dr. Baust is a recognized innovator and entrepreneur in cryomedicine and is a pioneer in the area of molecular mechanisms of cell death and low temperature stress. Dr. Baust has published over 100 papers, reviews, book chapters, abstracts, and patents in the area of low temperature biology and has been instrumental in the advancement of the field of cryobiology into the molecular biological era focusing on signal transduction and apoptosis. In this regard, Dr. Baust is credited with the discovery of cryopreservation-induced delayed-onset cell death. In the area of research and technology development, Dr. Baust has led the development of numerous medical devices, including the Supercritical Nitrogen (SCN) and Pressurized Nitrogen (PSN) cryoablation devices for the treatment of cancer and cardiac arrhythmias. This is in addition to spearheading the development of the SmartThaw and SmartFreeze devices for improved cell and tissue cryopreservation. Coupled with these technical engineering developments, he leads life science research programs focused on the cell-molecular actions of cryoablation. These efforts have resulted in the identification of a significant molecular stress response component to freezing injury which is responsible for the differential sensitivity of various cancers to thermal ablation. In addition to these activities, Dr. Baust serves on the editorial boards of Biopreservation and Biobanking as well as Technology in Cancer Research and Treatment, and is a reviewer for several other scientific journals. Dr. Baust co-edited the book Advances in Biopreservation, is a past board member for the Society for Cryobiology, and currently serves on the Board and as Treasurer of the American College of Cryosurgery. Dr. Baust completed his studies at Cornell University, State University of New York at Binghamton, and Harvard Medical School.
Continuous bioprocessing is rapidly gaining momentum, and seems likely to increase its role in manufacturing over the coming years. This is due to the benefits of operational flexibility and increased efficiency, product consistency, quality assurance, and significant cost savings. Implementing quality by design (QbD) principles and subsequent process validation into a continuous bioprocess poses a challenge, but also an opportunity to gain a robust process with assured drug quality. Viral safety assurance remains a critical aspect of bioprocessing of monoclonal antibodies (mAbs) and recombinant proteins. While robust virus clearance is well understood for batch processes, many questions remain on how to implement viral safety into continuous bioprocesses. For example, use of virus filtration in continuous bioprocessing is likely to involve low flow rates and significantly extended processing times compared to current batch applications. Applying QbD principles to understand the expected virus filter design space will be critical for successful implementation into continuous processing applications. Validation of viral filtration in continuous processing applications may also present new challenges. For example, careful consideration must be given to overcome potential virus viability issues or changes in the process fluid when testing for extended filtration times at low flow rates. Innovative test designs may be warranted to successfully validate virus filtration in continuous bioprocessing. Here we present data showing some process inputs that should be evaluated to determine critical control attributes for continuous bioprocessing applications. We also present data that show a robust virus filter design space is required for implementation into continuous bioprocessing applications. Specifically, our results show that high virus clearance can be achieved using worst-case test conditions to simulate virus filtration in a continuous bioprocess. Consideration is also given to the logistics of performing virus filtration over extended test durations.
Morven McAlister received her BSc degree in Applied Microbiology from the University of Strathclyde (UK). Her PhD was completed at Queen's University of Belfast (UK) in the field of bioremediation. In 1999 she researched microbial contamination and biofilm formation in high purity water systems at the University of Arizona in Tucson. She joined Pall in 2001, and has held various technical leadership roles focused on microbial contamination control, specifically for sterile and virus filtration applications. She has extensive experience in filter validation, and her current focus involves applying quality by design (QbD) principles to optimize sterility assurance in batch and continuous bioprocessing applications.