Globally Resilient Supply Chains
for Seasonal and Pandemic
Influenza Vaccines

Ravi Anupindi, Prashant Yadav, Kenisha M. P. Jefferson, and
Elizabeth Ashby, Editors

Committee on Addressing Issues of Vaccine Distribution and Supply
Chains to Advance Pandemic and Seasonal Influenza Preparedness and
Response

Board on Global Health

Health and Medicine Division

A Consensus Study Report of

THE NATIONAL ACADEMIES PRESS
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This activity was supported by a contract between the National Academy of Sciences and the Office of Global Affairs with the U.S. Department of Health and Human Services. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.

International Standard Book Number-13: 978-0-309-08915-9
International Standard Book Number-10: 0-309-08915-8
Digital Object Identifier: https://doi.org/10.17226/26285
Library of Congress Catalog Number: 2021951358

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2022. Globally resilient supply chains for seasonal and pandemic influenza vaccines. Washington, DC: The National Academies Press. https://doi.org/10.17226/26285.

COMMITTEE ON ADDRESSING ISSUES OF VACCINE DISTRIBUTION AND SUPPLY CHAINS TO ADVANCE PANDEMIC AND SEASONAL INFLUENZA PREPAREDNESS AND RESPONSE

RAVI ANUPINDI (Chair), Colonel William G. and Ann C. Svetlich Professor of Operations Research and Management, University of Michigan

PRASHANT YADAV (Vice Chair), Senior Fellow, Center for Global Development; Affiliate Professor, INSEAD, France; Lecturer, Harvard Medical School

MAHSHID ABIR, Senior Policy Researcher, RAND Corporation; Associate Professor, University of Michigan Medical School

RICK A. BRIGHT, Senior Vice President, Pandemic Prevention and Response, The Rockefeller Foundation

WILLIAM G. BUREL, President and Chief Executive Officer, Hamilton Grace, LLC

MATTHEW DOWNHAM, Sustainable Manufacturing Lead, Coalition for Epidemic Preparedness Innovations

NAGWA HASANIN, Senior Health Advisor, UNICEF

NOREEN A. HYNES, Associate Professor, Johns Hopkins University Schools of Medicine and Public Health

DAVID C. KASLOW, Chief Scientific Officer, PATH

PINAR KESKINOCAK, William W. George Chair and Professor and Director, Center for Health and Humanitarian Systems, Georgia Institute of Technology

SAAD B. OMER, Director, Yale Institute for Global Health

JENNIFER PANCORBO, Director of Industry Programs and Research, Biomanufacturing Training and Education Center, North Carolina State University

Study Staff

KENISHA M. P. JEFFERSON, Study Director

ELIZABETH ASHBY, Research Associate

EMILIE RYAN-CASTILLO, Senior Program Assistant

CLAIRE BIFFL, Senior Program Assistant

PATRICIA A. CUFF, Senior Program Officer

JULIE A. PAVLIN, Senior Director, Board on Global Health

Consultants

JOSEPH ALPER, Science Writer (until July 2021)

KEVIN FAHEY, Science Writer (from August 2021)

EUGENIA GROHMAN, Editor (from July 2021)

MELISSA MAITIN-SHEPARD, Science Writer (from July 2021)

JANAMARIE PERROUD, Technical Writer

Reviewers

This Consensus Study Report was reviewed in draft form by individuals 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 the institutional standards for 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 individuals for their review of this report:

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 this report was overseen by ANDY STERGACHIS,

University of Washington, and BOBBIE BERKOWITZ, Columbia University. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.

National Academy of Medicine

Advancing Pandemic and Seasonal Influenza Vaccine Preparedness and Response Series

This study, Globally Resilient Supply Chains for Seasonal and Pandemic Influenza Vaccines, provides recommendations on how to bolster vaccine distribution and enhance global vaccine development and manufacturing infrastructure for pandemic and seasonal influenza events, using lessons learned from COVID-19. It is one of four studies conducted under the Advancing Pandemic and Seasonal Influenza Vaccine Preparedness and Response Initiative, which explores how the scientific and technological breakthroughs throughout the COVID-19 pandemic could inform and advance future pandemic and seasonal influenza vaccine preparedness and response efforts.

The three companion studies to this study examine how the lessons learned from COVID-19 around vaccine research and development, public health interventions and countermeasures, and global coordination, partnerships, and financing could be best utilized to improve the development and distribution of pandemic and seasonal influenza vaccines. Together, the four consensus studies present a path toward better preparedness in addressing pandemic and seasonal influenza.

Launched by the National Academy of Medicine with support from the Office of Global Affairs, U.S. Department of Health and Human Services, the Advancing Pandemic and Seasonal Influenza Vaccine Preparedness and Response Initiative acknowledges that influenza is here to stay. The unprecedented scope of this initiative allowed for international experts to look at this issue from multiple angles and provide recommendations that set out a pathway to more effective influenza vaccines worldwide. Driven by international cooperation, this independent initiative provides a platform to highlight why we need to act as a global community to better prepare for pandemic and seasonal influenza.

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Acknowledgments

This report is a product of the cooperation and contributions of many people, all of whom helped address a very broad statement of task in an extremely short timeframe. The committee is especially grateful to all the external experts who provided invaluable input at committee meetings. Their names and affiliations can be found in the committee meeting agendas in Appendix C. This report would not be possible without the sponsorship of the U.S. Department of Health and Human Services’ Office of Global Affairs and the support from the National Academy of Medicine’s International Committee, which was integral in conceptualizing the study’s statement of task.

The committee also thanks Leslie Sim and Taryn Young for their flexibility and coordination during the review process as well as Lauren Shern for providing guidance throughout the course of the project. A special thank you to Victor Stewart and Ron Brown for quickly processing contracts and agreements throughout the life cycle of the study.

Our acknowledgments also extend to the directors of the partner influenza studies, Ellen Schenk, Hoda Soltani, and Janelle Winters, for their unwavering support and advice during the study process.

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Preface

The global COVID-19 pandemic has exposed serious weaknesses in the supply chain for vaccines and medical products. Many of these challenges have been managed with reactive responses by U.S. government agencies and global actors. However, these responses cannot hide the shortcomings in the current structures for managing vaccine supply chains before and during a pandemic. The supply chain challenges, which have unfolded throughout the COVID-19 pandemic, have exposed major weaknesses in the mechanisms of global coordination.

While the world is still struggling to manage the challenges in the global COVID-19 vaccine supply chain, everyone needs to prepare for a more robust vaccine supply chain to deal with future pandemics. Global health experts have long warned of the risks of influenza variants with potential to cause a pandemic. This committee was tasked with examining the supply chain and distribution challenges related to vaccines and vaccinations during the COVID-19 response (as well as past responses to SARS, H1N1, and Ebola), identify deficiencies in the global supply chain for pandemic and seasonal influenza, and develop recommendations for action by U.S. government agencies and global actors.

Vaccine manufacturing and distribution is a complex task. It requires hundreds of components, globally distributed high-quality biologic manufacturing capacity, a competent supply chain workforce, data and information tools, and financial resources for fast distribution and equitable deployment of vaccines. At a country level, getting vaccines into the arms of people also requires country preparedness and robust planning and the capability to adopt, distribute, deliver, and administer vaccines to appropri-

ate cohorts of people at scale. Vaccine characteristics and country access to a portfolio of vaccines also influence vaccine uptake and impact the efficiency of vaccine distribution and delivery.

In a global end-to-end supply chain, actions for different parts of this supply chain are made by different agencies and actors—from private firms to national governments, regional structures, global and UN agencies, and nongovernmental organizations. COVID-19 has also illustrated the devastating impact of a pandemic on the global economy and livelihoods, which necessitates considering roles for a broader set of actors. Health care and non–health care domains can engage in the vaccine supply chain to ensure a safer world through a whole-of-society approach.

The committee’s report takes stock of past actions and reports on seasonal and pandemic influenza vaccine manufacturing and distribution, looks at experiences and structures that have evolved for COVID-19 vaccines, and identifies deficiencies in the global supply chains for seasonal and pandemic influenza vaccines and also covers country preparedness and planning capabilities that need to be urgently addressed. The report points out technical areas and structural weaknesses that need to be strengthened and lays out mechanisms to strengthen coordination and information exchange systems in the global supply chain to ensure rapid and agile decision making to meet global vaccination needs equitably.

We hope that this report will provide clear guidance on the actions required by different stakeholders, both U.S. agencies and global actors, to build a robust and resilient global end-to-end supply chain for seasonal and pandemic influenza vaccines. Pursuing the recommendations in this report will not always be easy: the split of mandate, resourcing, and decision-making processes between national, regional, and global levels creates the need for embedding collaborative and coordinate efforts in existing agencies and structures. Everyone recognizes that for vaccine supply chains to work well during a pandemic, there is need for strong collaboration and coordination between a range of national, regional, and global actors in the supply chain, both public and private actors. If there is one key message that every reader should take away from this report, it is that this committee firmly believes that for the global vaccine supply chain to work well during a pandemic, many of the activities and coordination structures in the supply chain should be designed, created, and resourced during non-pandemic periods and not during a pandemic.

We thank first the members of committee, who committed their time and scientific expertise during an extremely busy period with their multiple roles. Ours was a very interdisciplinary committee, with experts of varied backgrounds in many different aspects of vaccine development, manufacturing, distribution, and policy. The committee members exhibited immense

patience and respect when discussing items, which for some were relatively straightforward and simple, and for others were new and complex.

Thanks also to National Academies of Sciences, Engineering, and Medicine staff, who helped us stay organized and focused and helped put our thoughts into writing. They worked tirelessly through our sessions, took notes, and iterated with many draft versions of this report. We also thank Janamarie Perroud for providing an overview of previous work on this subject, which was an important foundation for framing this study (see Appendix A). We are also grateful to the many experts who committed their time to present to the committee during public sessions.

Ravi Anupindi, Chair
Prashant Yadav, Vice Chair
Committee on Addressing Issues of Vaccine Distribution and
Supply Chains to Advance Pandemic and Seasonal Influenza
Preparedness and Response

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Contents

ACRONYMS AND ABBREVIATIONS

SUMMARY

1 INTRODUCTION

Understanding Influenza Viruses

Committee Task and Approach

Structure of the Report

References

2 INFLUENZA VIRUS AND INFLUENZA VACCINES: A PRIMER

Seasonal and Pandemic Influenza Viruses

Surveillance

Vaccine Development

Vaccine Production

Vaccine Production Platforms

Production Challenges

References

3 CRITICAL COMPONENTS FOR VACCINE MANUFACTURING

The Critical Components

Manufacturing Preparedness and Response

Forecasting Demand

Production

Stockpiling

Management and Allocation

Training and Readiness of Critical Workforce Personnel

Distributed Manufacturing Networks

References

4 VACCINE DISTRIBUTION AND DELIVERY

Design for Distribution

Vaccine Portfolios

Demand Forecasting and Generation

Global Distribution and Transportation

In-Country Storage and Distribution

Matching Supply and Demand

References

5 FRAMEWORKS, TOOLS, AND INNOVATIONS FOR DISTRIBUTION READINESS

Initiatives

Tools and Frameworks for Global Vaccination

Tools for Country Pandemic Preparedness

Innovations

References

6 BARRIERS, INCENTIVES, AND INNOVATIONS FOR SUSTAINABLE MANUFACTURING

Tradeoffs in Vaccine Development and Manufacturing

Barriers to Vaccine Manufacturing and Innovation

Facilitating Manufacturing Innovation

References

7 A WAY FORWARD

Vaccine Technologies and Innovations

An Integrated Approach Across the Vaccine Landscape

Final Thoughts

References

APPENDIXES

A REVIEW OF PREVIOUS RECOMMENDATIONS FOR PANDEMIC VACCINE MANUFACTURING

B BIOGRAPHICAL SKETCHES OF COMMITTEE MEMBERS AND STAFF

C AGENDAS: OPEN COMMITTEE MEETINGS

Boxes, Figures, and Tables

BOXES

1-1 Statement of Task

2-1 Adjuvants for Influenza Vaccines

3-1 The Defense Production Act

3-2 COVAX Marketplace for Critical Supplies

3-3 Regulatory Harmonization and Convergence for Improved Public Health

FIGURES

2-1 WHO Global Influenza Surveillance and Response System

2-2 Egg-based influenza vaccine manufacturing and timeline

2-3 Influenza vaccine response capability

2-4 Vaccine manufacturing network

3-1 Supply chain challenges along the value chain

3-2 Calculations of fixed costs for vaccine facilities in developing countries, based on four hypothetical scenarios

4-1 Nations with the largest share of exports for key vaccine components and supplies in 2018

TABLES

2-1 Key Characteristics of Influenza Subtypes

2-2 Stages of and Data for Seasonal Influenza Vaccine Development and Manufacturing

2-3 Comparative Characteristics of Selected Seasonal Influenza Vaccines

2-4 Influenza Vaccine Manufacturing Facilities by WHO Region

2-5 Novel Technology Platforms for Producing Influenza Vaccines

3-1 Summary of Recommendations on Critical Components for Vaccine Manufacturing

3-2 Examples of Vaccine Manufacturing Educational Structures

4-1 Summary of Recommendations on Vaccine Distribution and Delivery

5-1 Summary of Recommendations and Relevant Actors on Frameworks, Tools, and Innovations for Distribution Readiness

5-2 Innovations for Vaccine Development During COVID-19

6-1 Summary of Recommendations on Barriers, Incentives, and Innovations for Sustainable Manufacturing

6-2 Advantages and Disadvantages of Technology Platforms Used to Develop Vaccines

6-3 Non-U.S. Funding Options for No-Fault Compensation Mechanisms

6-4 Pros and Cons of Options for Housing a Vaccine Injury Compensation System

A-1 Pandemic Vaccine Manufacturing Recommendations in Chronological Order

A-2 Trends in Unimplemented Pandemic Vaccine Manufacturing Recommendations

Acronyms and Abbreviations

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