PAT Applied in Biopharmaceutical Process Development and Manufacturing An Enabling Tool for Quality-by-Design

As with all of pharmaceutical production, the regulatory environment for the production of therapeutics has been changing as a direct result of the US FDA-initiated Quality by Design (QbD) guidelines and corresponding activities of the International Committee for Harmonization (ICH). Given the rapid growth in the biopharmaceutical area and the complexity of the molecules, the optimum use of which are still being developed, there is a great need for flexible and proactive teams in order to satisfy the regulatory requirements during process development. Process Analytical Technologies (PAT) applied in biopharmaceutical process development and manufacturing have received significant attention in recent years as an enabler to the QbD paradigm. PAT Applied in Biopharmaceutical Process Development and Manufacturing covers technological advances in measurement sciences, data acquisition, monitoring, and control. Technical leaders present real-life case studies in areas including measuring and monitoring raw materials, cell culture, purification, and cleaning and lyophilization processes via advanced PAT. They also explore how data are collected and analyzed using advanced analytical techniques such as multivariate data analysis, monitoring, and control in real-time. Invaluable for experienced practitioners in PAT in biopharmaceuticals, this book is an excellent reference guide for regulatory officials and a vital training aid for students who need to learn the state of the art in this interdisciplinary and exciting area.

ForewordIntroductionMel Koch, Ray Chrisman, Duncan LowCHAPTER 1: Scientific and Regulatory Overview of PAT in BioprocessesRakhi B. Shah, Kurt A. Brorson, Erik K. Read, Jun T. Park, Christopher Watts, Mansoor A. KhanOffice of Pharmaceutical Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, USACHAPTER 2: A Strategic Vision for Integrated PAT and Advanced Control in Biologics ManufacturingMelissa M. St. Amand, Peter G. Millili, Meghan M. McCabe, Babatunde A. OgunnaikeUniversity of Delaware, USACHAPTER 3: Multivariate Techniques in Biopharmaceutical Process DevelopmentJeremy S. ConnerAmgen, Inc., USACHAPTER 4: Analysis, Monitoring, Control and Optimization of Batch Processes: Multivariate Dynamic Data ModelingTheodora KourtiGlaxoSmithKline, UKCHAPTER 5: Multivariate Data Analysis in BiopharmaceuticalsJoydeep Ganguly*, Louis Obando**, John P. Higgins**, Seongkyu Yoon**** Biogen-Idec Corp., USA, ** Merck Sharpe and DohmeCorp., USA, *** University of Massachusetts, Lowell, USACHAPTER 6: PAT Advances and Applications in Recombinant Protein Cell Culture ProcessesAna Veronica Carvalhal , Victor M. SaucedoGenentech, Inc., USACHAPTER 7: PAT Applied to Raw MaterialsErik SkibstedNovo Nordisk, DenmarkCHAPTER 8: PAT for Enhanced Verification of Bio-Process System CleaningPeter K. Watler*, Keith Bader*, John M. Hyde*, Shuichi Yamamoto***Hyde Engineering + Consulting, Inc., USA, **Yamaguchi University, Ube, JapanCHAPTER 9: Cell Culture PAT Multiplexing NIRMariana L. Fazenda, Linda M. Harvey, Brian McNeilUniversity of Strathclyde, Scotland, UKCHAPTER 10: Process Analytical Technology (PAT) for Bioseparation Unit OperationsA. S. Rathore, V. Ghare, and R. BhambureDepartment of Chemical Engineering, Indian Institute of Technology, New Delhi, India CHAPTER 11. PAT Use in Biofuels ManufacturingPedro Felizardo, José C. Menezes, M. Joana Neiva-CorreiaTechnical University of Lisbon, Lisbon, PortugalCHAPTER 12. Application of Micro Reactors for Innovative Bioprocess Development and ManufacturingSeth T. Rodgers and A. Peter RussoSeahorse Bioscience, San Francisco, CA, USACHAPTER 13: Real-time Monitoring and Controlling of Lyophilization Process Parameters through PAT ToolsFeroz Jameel*, William J. Kessler***Amgen, Inc., USA **Physical Sciences Inc., USACHAPTER 14: Process Analytical Technologies’ Role in Operational ExcellenceFetanet Ceylan Erzen*, Manbir Sodhi***Amgen, Inc., USA, **University of Rhode Island, USACHAPTER 15: Conclusions, Current Status and Future Vision of PAT in BiologicsDuncan Low*, Ray Chrisman***Amgen Inc., USA, **University of Washington, USA

Dr. Cenk Undey joined Process Development at Amgen in 2003, where he currently leads the Process and Systems Analysis in Global Process Engineering & Product Engineering group. His division is responsible for providing data management across product lifecycles, developing and deploying advanced real-time multivariate monitoring and control technologies, supporting process monitoring programs and systems, conducting manufacturing process analysis via advanced data analytical methods, and applying systems theory for process troubleshooting and optimization.He led the development and implementation of Multivariate Data Analysis and Real-time Multivariate Statistical Process Monitoring technology in cGMP for use in manufacturing floor during his tenure at Amgen, resulting in significant process improvements. Dr. Undey has industrial experience with PAT tools currently in use in bio/pharmaceuticals manufacturing and is on the steering committee of Pharmaceutical Process Analytics Roundtable. He holds B.Sc., M.Sc. and Ph.D. degrees in Chemical Engineering from Istanbul University, Turkey, and conducted postdoctoral research in Process Modeling, Monitoring and Control group in the Department of Chemical and Biological Engineering at Illinois Institute of Technology, Chicago, USA. Dr. Duncan Low joined the Process Development Department at Amgen in 2003, where he is currently responsible for Materials Science. He leads cross-functional teams for materials and technology evaluation, technology development, and Process Analytical Technology. He is a member of the ISPE Executive Committee for PAT, is a member of USP’s Committee of Experts, and chairs the ASTM E55.01 subcommittee which develops consensus standards for Manufacturers of Pharmaceutical Products. Prior to joining Amgen, he held VP positions at Millipore and Pharmacia Biotech. He has extensive experience of the tools currently in use for upstream and downstream processing and has worked closely with applications development throughout the industry. He has an M.A. in Biochemistry from the University of Cambridge and a Ph.D. in Microbiology from the University of Glasgow. Prof. Jose Cardoso de Menezes coordinates a Systems Engineering group at the Technical University of Lisbon (IST), Centre for Biological and Chemical Engineering, working in PAT, Chemometrics and Multivariate Statistics for over 10 years. He has a Chemical Engineering degree, M.A. in Catalysis,Ph.D. in Biochemical Engineering,and aPost-Doctorate in advanced monitoring of bioprocesses. Currently, he is an Invited Associate Professor of Faculty at Pharmacy of Lisbon University (FPLU) and has recently started his own company to exploit PAT implementations in industry. Also, he founded and coordinated for the past 3 years a Masters Program in Pharmaceutical Engineering, jointly taught by IST and FPLU, which covers PAT and PAT disciplines such as QbD, DOE, NIR and other monitoring, modeling and control techniques. He is a member of ISPE, as well as other organizations, has published extensively, and taught many Ph.D. and M.Sc. students on the above subjects. Dr. Melvin V. Koch is the executive director of the Center for Process Analysis and Control (CPAC) and Affiliate Professor of Chemical Engineering at the University of Washington in Seattle. He received a B.A. in Chemistry and Mathematics from St Olaf College, M.S. in biochemistry, and Ph.D. in Organic Medicinal Chemistry from the University of Iowa. Dr. Koch previously worked for The Dow Chemical Company in process research and analytical chemistry, achieving the level of Global Director of Analytical Sciences. Currently, he is active with coordinating developments in the field of process analytical technology (PAT) between industry, government agencies, and academia. Dr. Koch has served on the FDA advisory committee to the Office of Pharmaceutical Sciences and on review committees of several US National Laboratories.