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Continuous Manufacturing for the Modernization of Pharmaceutical Production: Proceedings of a Workshop (2019)

Chapter: Appendix C: Running Themes Across Workshop Sessions

« Previous: Appendix B: Biographies of Planning Committee Members, Speakers, and National Academies of Sciences, Engineering, and Medicine Staff
Suggested Citation:"Appendix C: Running Themes Across Workshop Sessions." National Academies of Sciences, Engineering, and Medicine. 2019. Continuous Manufacturing for the Modernization of Pharmaceutical Production: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25340.
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Appendix C

Running Themes Across Workshop Sessions

TABLE C-1 Technologies and Issues Raised with Respect to Regulations

Topic Organization Speaker Technologies/Issues Addressed
Science of Pharma Manufacturing FDA Janet Woodcock FDA’s interest in furthering science of continuous manufacturing requires collaboration with industry, academia, and other federal sponsors.
Medical Countermeasures BARDA Rick Bright BARDA focuses on rapidly producing medical countermeasures to changing natural and manmade security threats.
United States and International Regulatory Considerations Nasr Regulatory Consulting Moheb Nasr White papers are available on both small molecules and biologics. There is a regulatory framework adequate to support continuous manufacturing: Good Manufacturing Practices (GMPs), the critical quality attributes (CQAs), and the Points to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Q13 guideline.
Real-time Product Release and Adaptive Process Control; Process Analytical Technology Merck Doug Richardson Merck’s experience: measure CQA; model Process; apply appropriate control strategy; use lessons learned to optimize process; and remember that there is “no path to real-time release without process analytical.”
Viral Safety Guideline ICH Q5A Just Biotherapeutics Lisa ConnellyCrowley Robust and effective viral clearance of retrovirus-like particles is critical.
Suggested Citation:"Appendix C: Running Themes Across Workshop Sessions." National Academies of Sciences, Engineering, and Medicine. 2019. Continuous Manufacturing for the Modernization of Pharmaceutical Production: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25340.
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TABLE C-2 Technologies and Issues Raised with Respect to Regulations

Topic Organization Speaker Technologies/Issues Addressed
Perfusion Amgen Art Hewig Shrinking the manufacturing footprint and capital investment is needed. Perfusion gives high titers; 25 to 60 g/L continuous manufacturing will be company specific.
One-room production, critical quality attributes Janssen Maricio Futran One room operation enables continuous monitoring; ability to monitor CQA during (rather than after) production is critical.
Perfusion Sanofi Shawn Barrett Sanofi is moving from microcarrier Chinese hamster ovary (CHO) culture to suspension CHO culture with continuous capture. Intensified perfusion platform yields 100 × increase in productivity.
Continuous downstream processing with continuous upstream processing demonstrated MedImmune Lindsay Arnold MedImmune has operated continuous downstream processing for two weeks: Protein A capture, low pH virus inactivation, filter train, multi-column chromatography, single pass buffer exchange, and final concentration has been run with continuous upstream.
Developed integrated, skid mounted single-use technology Boehringer Ingelheim Daisie Ogawa The process has run continuously with no “air-gaps;” process has increased productivity by 2 to 6 × 4 × reduction in media volume, with potential to manufacture multiple products.
Using experiences from food industry Pfizer Satashi Ontake Note pros and cons of integrated versus piecemeal continuous processing.

TABLE C-3 Unit Operations and Input to Process Models

Topic Organization Speaker Technologies/Issues Addressed
Science of Pharmaceutical Manufacturing FDA Janet Woodcock A challenge is the integration of downstream unit operations in an effective manner that satisfies purity requirements.
Making the business case for continuous manufacturing Janssen Pharmaceuticals Mauricio Futran Known unit operations lower the hurdle to implementing continuous processes.
Suggested Citation:"Appendix C: Running Themes Across Workshop Sessions." National Academies of Sciences, Engineering, and Medicine. 2019. Continuous Manufacturing for the Modernization of Pharmaceutical Production: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25340.
×
Topic Organization Speaker Technologies/Issues Addressed
Downstream processing Merck Mark Brower Labs can be used to test unit operations and help provide information to design new systems.
Achieving full integration Massachusetts Institute of Technology Richard Braatz Achieving full automation requires complete understanding of each unit operation. In silico models and dynamic models can increase understanding of unit operations for plant-wide simulation and control design.
Considerations for integration Roche Veena Warikoo Intensified processes means fewer unit operations, but there needs to be more columns and column cycles and liquid flow rates could be controlled continuously so that they are synchronous as a means of mitigating deviations.

TABLE C-4 Discussion of Business Case in Technical Sessions

Topic Organization Speaker Technologies/Issues Addressed
Downstream processing MedImmune Lindsay Arnold The business cases vary based on the particular set of drivers that are important to the company, such as safety, cash flow, capital reduction, space constraints, and capital improvement, and will vary between clinical and commercial settings.
Using digital biomanufacturing to support product manufacturing GE Healthcare William Whitford Digital biomanufacturing should also support business continuity with incident control, management, and reporting capabilities, and in-line or on-line, real-time, orthogonal process monitoring and adaptive control.
Considerations for integration Roche Veena Warikoo There will not be a business case for continuous manufacturing without process intensification. Product intensification challenges business models, opening opportunities for new patentable products, process chemistry, and change to just in time or distributed manufacturing.
Suggested Citation:"Appendix C: Running Themes Across Workshop Sessions." National Academies of Sciences, Engineering, and Medicine. 2019. Continuous Manufacturing for the Modernization of Pharmaceutical Production: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25340.
×
Page 58
Suggested Citation:"Appendix C: Running Themes Across Workshop Sessions." National Academies of Sciences, Engineering, and Medicine. 2019. Continuous Manufacturing for the Modernization of Pharmaceutical Production: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25340.
×
Page 59
Suggested Citation:"Appendix C: Running Themes Across Workshop Sessions." National Academies of Sciences, Engineering, and Medicine. 2019. Continuous Manufacturing for the Modernization of Pharmaceutical Production: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25340.
×
Page 60
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On July 30-31, 2018, the National Academies of Sciences, Engineering, and Medicine held a workshop titled Continuous Manufacturing for the Modernization of Pharmaceutical Production. This workshop discussed the business and regulatory concerns associated with adopting continuous manufacturing techniques to produce biologics such as enzymes, monoclonal antibodies, and vaccines. The participants also discussed specific challenges for integration across the manufacturing system, including upstream and downstream processes, analytical techniques, and drug product development. The workshop addressed these challenges broadly across the biologics domain but focused particularly on drug categories of greatest FDA and industrial interest such as monoclonal antibodies and vaccines. This publication summarizes the presentations and discussions from the workshop.

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