1st Edition

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

Edited By Cenk Undey, Duncan Low, Jose C. Menezes, Mel Koch Copyright 2012
    328 Pages 125 B/W Illustrations
    by CRC Press

    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.


    Mel Koch, Ray Chrisman, Duncan Low

    CHAPTER 1: Scientific and Regulatory Overview of PAT in Bioprocesses
    Rakhi B. Shah, Kurt A. Brorson, Erik K. Read, Jun T. Park, Christopher Watts, Mansoor A. Khan
    Office of Pharmaceutical Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, USA

    CHAPTER 2: A Strategic Vision for Integrated PAT and Advanced Control in Biologics Manufacturing
    Melissa M. St. Amand, Peter G. Millili, Meghan M. McCabe, Babatunde A. Ogunnaike
    University of Delaware, USA

    CHAPTER 3: Multivariate Techniques in Biopharmaceutical Process Development
    Jeremy S. Conner
    Amgen, Inc., USA

    CHAPTER 4: Analysis, Monitoring, Control and Optimization of Batch Processes: Multivariate Dynamic Data Modeling
    Theodora Kourti
    GlaxoSmithKline, UK

    CHAPTER 5: Multivariate Data Analysis in Biopharmaceuticals
    Joydeep Ganguly*, Louis Obando**, John P. Higgins**, Seongkyu Yoon***
    * Biogen-Idec Corp., USA, ** Merck Sharpe and DohmeCorp., USA, *** University of Massachusetts, Lowell, USA

    CHAPTER 6: PAT Advances and Applications in Recombinant Protein Cell Culture Processes
    Ana Veronica Carvalhal , Victor M. Saucedo
    Genentech, Inc., USA

    CHAPTER 7: PAT Applied to Raw Materials
    Erik Skibsted
    Novo Nordisk, Denmark

    CHAPTER 8: PAT for Enhanced Verification of Bio-Process System Cleaning
    Peter K. Watler*, Keith Bader*, John M. Hyde*, Shuichi Yamamoto**
    *Hyde Engineering + Consulting, Inc., USA, **Yamaguchi University, Ube, Japan

    CHAPTER 9: Cell Culture PAT Multiplexing NIR
    Mariana L. Fazenda, Linda M. Harvey, Brian McNeil
    University of Strathclyde, Scotland, UK

    CHAPTER 10: Process Analytical Technology (PAT) for Bioseparation Unit Operations
    A. S. Rathore, V. Ghare, and R. Bhambure
    Department of Chemical Engineering, Indian Institute of Technology, New Delhi, India  

    CHAPTER 11. PAT Use in Biofuels Manufacturing
    Pedro Felizardo, José C. Menezes, M. Joana Neiva-Correia
    Technical University of Lisbon, Lisbon, Portugal

    CHAPTER 12. Application of Micro Reactors for Innovative Bioprocess Development and Manufacturing
    Seth T. Rodgers and A. Peter Russo
    Seahorse Bioscience, San Francisco, CA, USA

    CHAPTER 13: Real-time Monitoring and Controlling of Lyophilization Process Parameters through PAT Tools
    Feroz Jameel*, William J. Kessler**
    *Amgen, Inc., USA **Physical Sciences Inc., USA

    CHAPTER 14: Process Analytical Technologies’ Role in Operational Excellence
    Fetanet Ceylan Erzen*, Manbir Sodhi**
    *Amgen, Inc., USA, **University of Rhode Island, USA

    CHAPTER 15: Conclusions, Current Status and Future Vision of PAT in Biologics
    Duncan 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