Innovations in
PHARMACEUTICAL
MANUFACTURING
on the Horizon
Technical Challenges, Regulatory Issues,
and Recommendations
Committee to Identify Innovative Technologies to Advance
Pharmaceutical Manufacturing
Board on Chemical Sciences and Technology
Division on Earth and Life Studies
A Consensus Study Report of
THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu
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This project was supported by Contract 75F40119C10045 between the National Academies of Sciences, Engineering, and Medicine and the Department of Health and Human Services. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the organizations or agencies that provided support for this project.
International Standard Book Number-13: 978-0-309-08867-1
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Digital Object Identifier: https://doi.org/10.17226/26009
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2021. Innovations in Pharmaceutical Manufacturing on the Horizon: Technical Challenges, Regulatory Issues, and Recommendations. Washington, DC: The National Academies Press. https://doi.org/10.17226/26009.
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COMMITTEE TO IDENTIFY INNOVATIVE TECHNOLOGIES TO ADVANCE PHARMACEUTICAL MANUFACTURING1
Members
GINTARAS REKLAITIS (NAE) (Chair), Purdue University, IN
TIMOTHY CHARLEBOIS, Pfizer Inc, MA
MATTHEW DELISA, Cornell University, NY
CHRISTOPHER EARNHART, U.S. Army, Department of Defense, MD
STEPHEN W. HADLEY, Bill & Melinda Gates Foundation, WA
ARLENE JOYNER, U.S. Department of Health and Human Services, Washington, DC
KATHERINE LEWIS, Lawrence Livermore National Laboratory, CA
PAUL MORT, Purdue University, IN
TODD PRZYBYCIEN, Rensselaer Polytechnic Institute, NY
KELLEY ROGERS, National Institute of Standards and Technology, MD
SALY ROMERO-TORRES, Thermo Fisher Scientific, NC
GREGORY STEPHANOPOULOS (NAE), Massachusetts Institute of Technology, MA
SEONGKYU YOON, University of Massachusetts Lowell, MA
Staff
ELLEN K. MANTUS, Project Director
MARILEE SHELTON-DAVENPORT, Senior Program Officer
RADIAH ROSE-CRAWFORD, Manager, Editorial Projects
KESIAH CLEMENT, Senior Program Assistant
Sponsor
FOOD AND DRUG ADMINISTRATION
___________________
1 See Appendix B, Disclosure of Conflict(s) of Interest.
BOARD ON CHEMICAL SCIENCES AND TECHNOLOGY
Co-Chairs
SCOTT COLLICK, DuPont
JENNIFER SINCLAIR CURTIS, University of California, Davis
Members
GERARD BAILLELY, Procter and Gamble
RUBEN G. CARBONELL (NAE), North Carolina State University
JOHN FORTNER, Yale School of Engineering and Applied Science
SAMUEL H. GELLMAN (NAS), University of Wisconsin-Madison
KAREN I. GOLDBERG (NAS), University of Pennsylvania
TIMOTHY HALL, McNesse State University
MIRIAM E. JOHN, Sandia National Laboratories (Ret.)
JODIE L. LUTKENHAUS, Texas A&M University
JOSEPH B. POWELL, Shell Global
PETER ROSSKY (NAS), Rice University
REBECCA T. RUCK, Merck Process Research & Development
RICHMOND SARPONG, University of California, Berkeley
VIJAY SWARUP, ExxonMobil
SALY ROMERO-TORRES, Thermo Fisher Scientific
Staff
JEREMY T. MATHIS, Board Director
ELLEN MANTUS, Scholar
MARILEE SHELTON-DAVENPORT, Senior Program Officer
MAGGIE WALSER, Senior Program Officer
NICHOLAS ROGERS, Financial Associate
JESSICA WOLFMAN, Research Associate
KESIAH CLEMENT, Senior Program Assistant
SARAH HARPER, Program Assistant
OLIVIA TORBERT, Program Assistant
BENJAMIN ULRICH, Program Assistant
ELISE ZAIDI, Communications & Media Associate
Acknowledgments
This Consensus Study Report was reviewed in draft form by persons chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets institutional standards of quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.
We thank the following for their review of this report:
Matthew Bio, Snapdragon Chemistry
Richard D. Braatz (NAE), Massachusetts Institute of Technology
Barry Coller (NAS/NAM), The Rockefeller University
Margaret Hamburg (NAM), National Academy of Medicine
Klavs Jensen (NAS/NAE), Massachusetts Institute of Technology
Christine Moore, Merck
Jean Tom (NAE), Bristol-Myers Squibb
Greg Troiano, BIND Therapeutics
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report, nor did they see the final draft before its release. The review of the report was overseen by Babatunde A. Ogunnaike (NAE) and Stephen W Drew (NAE) who were responsible for making certain that an independent examination of the report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.
The completion of this study would not have been successful without the assistance of many individuals and organizations. The committee thanks especially the following for their contributions: Noubar Afeyan, Flagship Pioneering; Karin Balss, Janssen; Akilesh Bhambhani, Merck; Dan Blackwood, Pfizer; Andy Bommarius, Georgia Institute of Technology; Richard Braatz, Massachusetts Institute of Technology; Jon Coffman, AstraZeneca; Paul Collins, Lilly; Mauricio Futran, Janssen; David Gaugh, Association for Accessible Medicines; Susan Hershenson, Bill & Melinda Gates Foundation; Jun Huang, Pfizer; Günter Jagschies, GE Healthcare (Retired); Amy Jenkins, Defense Advanced Research Projects Agency; Mansoor Khan, Texas A&M University; Michael Kopcha, Food and Drug Administration (FDA); Richard Korsmeyer, Consultant; Sau (Larry) Lee, FDA; David Lechuga-Ballesteros, AstraZeneca; Kelvin Lee, University of Delaware; Brent Lieffers, Singota Solutions; Kerry Love, Sunflower Therapeutics; Gustavo Mahler, Dynamk Capital; Salvatore Mascia, Continuus; Christine Moore, Merck; Steve Nail, Baxter; Roger Nosal, Pfizer; Gregg Nyberg, Merck; Lisa Parks, Association for Accessible Medicines; Jack Prior, Sanofi; Govind Rao, University of Maryland; John Schiel, National Institute of Standards and Technology; Patricia Seymour, BDO; Jason Starkey, Pfizer; Patrick Swann, Amgen; Jim Thomas, Just – Evotec Biologics; Jorg Thommes, Bill & Melinda Gates Medical Research Institute; Jean Tom, Bristol-Myers Squibb; Katherine Tyner, FDA; Kim Wolfram, Biogen; Janet Woodcock, FDA; Jae Yoo, Aprecia; and Ping Zhao, Bill & Melinda Gates Foundation.
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Contents
The Pharmaceutical Industry Today and Innovation
The Food and Drug Administration and Innovation
The Committee’s Approach to Its Task
2 INNOVATIONS IN MANUFACTURING DRUG SUBSTANCES
Process Innovations That Create New Stream Compositions
Overcoming Regulatory Challenges
3 INNOVATIONS IN MANUFACTURING DRUG PRODUCTS
Innovations in Manufacturing Approaches for Conventional Drug Products
Enabling New Forms of Drug Products
Enabling New Drug-Product Formulations: Novel Excipients
Overcoming Regulatory Challenges
4 NEW CONTROL APPROACHES TO ENABLE QUALITY ASSURANCE AND PROCESS CAPABILITY
Data Analytics and System Modeling
Overcoming Regulatory Challenges
5 INNOVATIONS IN INTEGRATED, FLEXIBLE, AND DISTRIBUTED MANUFACTURING NETWORKS
Key Technical Challenges for Innovations
Key Regulatory Challenges to Innovations
6 ADVANCING INNOVATION: OBSERVATIONS, CHALLENGES, OPPORTUNITIES, AND RECOMMENDATIONS
The Need for Incentives to Advance Technology Innovation
The Need for Global Convergence and Harmonization
Post-Approval Changes: Essential for Accelerating Innovation
Challenges Within the Sphere of FDA Influence in Supporting and Enabling Innovation
B DISCLOSURE OF UNAVOIDABLE CONFLICTS OF INTEREST
C WORKSHOP AND WEBINAR AGENDAS
D INNOVATIONS IN PHARMACUETICAL MANUFACTURING: PROCEEDING OF A WORKHSOP—IN BRIEF
E BARRIERS TO INNOVATIONS IN PHARMACEUTICAL MANUFACTURING: PROCEEDINGS OF A WORKSHOP—IN BRIEF
