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June 11-13, 2019 • MIT, Cambridge, MA
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John Aunins

John Aunins, PhD view bio | back to agenda
Executive Vice President & Chief Technology Officer, Seres Therapeutics, Inc.

Bioprocessing for Vaccine Viruses and Vectors

Viruses are perhaps the most potent immunization vectors known to man, owing to their repetitive presentation of antigens, and their ability to replicate in the case of live virus vaccines. When engineered with recombinant DNA techniques, they are also highly useful as vectors to deliver other antigens, or to create gene therapies for either in vitro cellular transduction, or in vivo gene delivery for purposes of genetic correction, immunotherapy, or tumor lysis. This lecture will discuss types of viral products, the development issues to be addressed, and principles of virus production and optimization using case studies for particular products.

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Paul Barone

Paul W. Barone, PhD view bio | back to agenda
Director, Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB), Center for Biomedical Innovation, Massachusetts Institute of Technology

Lessons from the MIT Consortium on Adventitious Agent Contamination in Biomanufacturing

Adventitious agent contamination of cell culture-based biomanufacturing operations for the production of protein and monoclonal antibody biotherapeutics are infrequent, but when they do occur, they are very costly, impact manufacturing operations, and can potentially impact patient safety and product supply. In response to this need, the MIT Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) began the confidential collection and analysis of industry-wide viral contamination data with an emphasis on “lessons learned”. The mission of the CAACB is to pool and to share knowledge, experience and practices in the area of adventitious agent contamination in biomanufacturing. The Consortium is providing a safe and collaborative environment for networking and information exchange focused on identifying best industry practices in contamination response, corrective and preventive actions, and promoting the development of new technologies to detect adventitious agents and mitigate risk of contamination. This presentation will cover the learnings from this study, including identified industry risks and best practices to mitigate those risks. This talk will discuss some of the lessons learned from the collaborative work done by the CAACB and their implications for vaccine manufacture.

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Dan Barouch, MD, PhD

Dan Barouch, MD, PhD view bio | back to agenda
Director, Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center;
Professor of Medicine, Harvard Medical School

Preclinical and Clinical Development of an HIV Vaccine

We have reported the protective efficacy of Ad26/MVA and Ad26/Env vaccines against SIVmac251 and SHIV-SF162P3 challenges in rhesus monkeys. In this presentation, I will provide an update of preclinical data, immune correlates of protection, and early phase clinical data with these vaccine regimens. I will also review the process we used for selecting a vaccine regimen for further development and outline ongoing studies and plans for clinical efficacy studies.

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Barry C. Buckland

Barry C. Buckland, PhD view bio | back to agenda
Chief Executive Officer, BiologicB, LLC

Introduction to Vaccine Development with Case Studies on Rotavirus, HPV, and Influenza

An overview will be presented of the various technical challenges for developing and manufacturing vaccines. This will be followed by a more detailed discussion around a Rotavirus vaccine, an HPV vaccine and an Influenza vaccine. More detailed information can be found in the following publications.

Buckland, Barry C. “The Process Development Challenge for a New Vaccine “. Nature Medicine. 11 (2005). S16 to S19
Jessica Josefsberg and Barry C. Buckland. “Vaccine Process Technology” Biotechnology and Bioengineering 109 (1443 to 1460) 2012
Barry C. Buckland. The Development and Manufacture of Influenza vaccines. Human Vaccines and Immunotherapeutics. 11 1357-1360 2015

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Castillo

José Castillo, PhD view bio | back to agenda
Co-Founder and Chief Technology Officer, Univercells S.A.

Innovative USP/DSP Approaches Applied to Viral Vaccines

Univercells has developed a vaccine manufacturing platform based on innovative upstream and downstream approaches aiming at increasing the availability of vaccines - the NevoLine™ system. This simulated continuous and automated platform integrates both USP and DSP processes and is encapsulated into isolators, making it a self-contained production unit (10 m²). The technology relies on a fixed-bed high density bioreactor operated in perfusion chained with sequential in-line clarification, downstream filtration and polishing steps to (a) decrease batch time, (b) reduce equipment utilization, (c) optimize utilities consumption and (d) intensify operations. This presentation will illustrate the NevoLine proof of concept polio vaccine production, achieving large capacities at low CoGs (< $0.30/dose) and CAPEX (< $30M) and leading to a tremendous impact on the factory design.

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Downham

Matthew Downham, PhD view bio | back to agenda
Associate Director, AstraZeneca

Influenza Vaccine Development and Manufacture

Understanding the symptoms, mortality impact and prevalence of influenza provides context to the importance of effective seasonal flu vaccines and vaccination. The physiology of influenza, as well as complexities of its seasonal epidemiology and antigenic change drives vaccine strain selection that also underpins epidemic / pandemic influenza preparedness. Synchronising the global influenza surveillance response with manufacture to meet annual supply of a matched flu vaccine strain, illustrates the challenges of protecting against a pathogen that is a master of disguise. How these challenges are met will be addressed whilst considering development and manufacture of Live Attenuated Influenza Vaccine (LAIV). Vaccination with LAIV demonstrates the benefits of mucosal immunity, whilst determining the correlates of protection for novel flu vaccines continue to challenge the flu vaccine industry. A case study will be used to illustrate how seasonal influenza campaign timing, planning and global surveillance are crucial to ensure the correct vaccine is supplied to market on time to effectively protect patients from influenza.

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Mark Feinberg

Mark Feinberg, PhD view bio | back to agenda
President and Chief Executive Officer, International AIDS Vaccine Initiative

Keynote: Enabling Affordable Global Access to Monoclonal Antibodies Through Innovative Technologies and Partnerships

Monoclonal antibody (mAb) technologies have had a profound impact on modern medicine and transformed the treatment of a wide range of malignant, autoimmune and infectious diseases. Currently, 6 of the 10 top-selling medical treatments globally are mAb-based injectable drugs.Novel antibodies in development also show promise for treating and preventing life-threatening diseases of global concern including HIV, influenza, bacterial infections, and snakebite envenoming (many of which health threats have a disproportionate impact in low income countries). However, the availability and access to life-saving and enhancing mAbs are currently almost entirely limited to wealthy or well-insured individuals in high-income countries. High prices, inadequate public health infrastructure, policy, procurement, and financing frameworks are blocking equitable global access to antibody products.We all collectively have an opportunity and responsibility to forge innovative public-private partnerships to translate disruptive technologies in the product optimization, manufacturing and delivery space into low-cost antibodies, and re-imagine policy frameworks and business models to enable broad access to important globally-relevant mAbs.

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Stefanie Frank

Stefanie Frank, PhD view bio | back to agenda
Lecturer in Synthetic Biology; Modular Training for the Bioprocess Industries (MBI), Module Leader Vaccine Bioprocess Development and Commercialisation, University College London

Introduction to the Future Vaccine Manufacturing Research Hub (Vax-Hub)

Reaching more people, especially children with vaccines and responding to epidemics remains challenging due to limitations in manufacturing capacity, distribution and cost of vaccines. The Future Vaccine Manufacturing Research Hub (Vax-Hub) supports an ambitious programme that seeks to tackle these issues through innovative research.The Vax-Hub is UK-funded via the Department of Health and Social Care and managed by the Engineering and Physical Sciences Research Council (EPSRC). It brings together multidisciplinary teams from academia, industry and policy makers with the vision to develop new technologies, platform manufacturing, better analytics and technologies that are widely applicable to the most common vaccine types used by the industry and will benefit low- and middle-income countries. The talk will give an overview of the Future Vaccine Manufacturing Research Hub, its interactions with other networks and a selection of research highlights.

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Adrian Hill

Adrian Hill, PhD view bio | back to agenda
Professor of Human Genetics; Director, The Jenner Institute, Oxford University

Ebola Vaccines: A Remarkable but Unfinished Story

The West African Ebola outbreak in 2014-2015 was a public health emergency of international concern and a wake-up call to the global community to recognise the risks posed by many outbreak pathogens. We were lucky that the outbreak could finally be controlled, perhaps just in time, with little contribution from the vaccines rushed into clinical development during the outbreak. We were even more fortunate that these vaccines had largely already been manufactured for a quite different objective: protection of north Americans from a potential bioterrorist attack. Today a substantial outbreak, with almost 2,000 cases, continues in the Democratic Republic of the Congo. I will review some of the major challenges undertaking rapid clinical development and biomanufacture during the West African outbreak, summarise progress toward useful vaccines as public health tools, and identify some of the recently recognised generic priorities for protection of populations by vaccines from new emerging pathogens.

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Kolodziej

Steve A. Kolodziej, PhD view bio | back to agenda
Associate Research Fellow, Pfizer, Inc.

Development of Capsular Polysaccharide Conjugate Vaccines

The manufacture of conjugate vaccines is a very complex process. Carrier proteins and capsular polysaccharides are produced by fermentation processes, while capsular polysaccharide activation and conjugation to the carrier protein are chemically mediated. Process development requires a cross-discipline team of scientists with backgrounds in analytical chemistry, biochemistry, bioprocess, chemistry, engineering, statistics, and vaccines research. Throughout the development process, care must be taken to ensure that the physicochemical, biochemical, and immunogenic properties of the conjugate are consistently maintained across production scales. This talk will highlight some of the manufacturing and development challenges encountered with conjugate vaccines and potential mitigations.

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J. Christopher Love, PhD

J. Christopher Love, PhD view bio | back to agenda
Associate Professor of Chemical Engineering, Koch Institute, Massachusetts Institute of Technology

Micro-Modular Manufacturing for Vaccines and Biopharmaceuticals

Biological knowledge of infectious diseases and other diseases, such as cancer, is growing at an accelerated pace. Implications of this knowledge are improved stratification of diseases, possibilities for personalized treatments, and explicit understanding of protective immune responses to be elicited by vaccines. It is becoming feasible to engineer vaccines for specific responses rather than relying on empirical development.The challenge of routine, low-cost manufacturing of vaccines creates a barrier to transforming health care globally.

Vaccines today do not benefit from well-defined, platform-like processes and concepts such as continuous bioprocess for manufacturing. Our InSCyT platform is an advanced prototype manufacturing system that provides integrated and automated production and purification of multiple protein therapeutics. The system allows end-to-end manufacturing of 100's to 10,000's of doses of recombinant protein drugs in days using a fast-growing, tractable microbial host (Pichia pastoris) and continuous processing for automated, hands-free purification through simple 2- or 3-stage chromatographic processes.As part of a Gates Foundation-funded Grand Challenge called ULTRA, we assessed the feasibility of manufacturing millions of doses of a trivalent recombinant rotavirus vaccine annually on a small-scale production system like InSCyT. Integrated bioprocessing could offer potential advantages for routine production in local regions with minimal infrastructure, and for democratization of manufacturing capacity for new vaccine concepts and personalized treatments in cancer.

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Tarit Mukhopadhyay, EngD

Tarit Mukhopadhyay, EngD view bio | back to agenda
Associate Vice President, Vaccine Process Research & Development, Merck & Co., Inc.

Challenges and Opportunities in Vaccine Manufacturing

While perhaps one of the most cost effective health interventions, vaccines are not profitable. The consequence of which has resulted in a lack of investment into process development and manufacturing technologies for vaccine development. This talk will discuss those challenges and opportunities in vaccine development and manufacturing, and how new technologies and predictive scale-down tools can help advance candidates into manufacture. Understanding the link to process economics will also be essential such that these solutions may be suitable for low income settings and advance vaccination programmes in the countries with poor immunisation rates.

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Derek O’Hagan

Derek O’Hagan, PhD view bio | back to agenda
Fellow and Senior Advisor, GlaxoSmithKline

Formulating Potent and Safe Delivery Systems for a Broad Range of Vaccines

Rapid progresses in molecular immunology has advanced vaccine adjuvant discovery efforts, enabling the use of cellular and target based assays to screen large collections of chemical compounds for potential use as immune potentiators. However the question remains as to how to safely and effectively deliver these new adjuvant compounds, particularly for use in existing vaccines which commonly use insoluble aluminium salts as adjuvants. Here we describe a novel approach to enable recently discovered adjuvant active compounds called Small Molecule Immune Potentiators (SMIPs) to adsorb to aluminum hydroxide adjuvant via the mechanism of ligand exchange. A phosphonate group has been chemically linked to the compounds to enable adsorption to aluminium hydroxide and here we present extensive formulation characterization, and an overview of the in vitro and in vivo performance of the new generation adjuvants. In addition, we will address the challenges for formulation and delivery of a large and complex nucleic acid (RNA) that needs to be protected against degradation and also delivered effectively into cells to enable the induction of potent immune responses. We will compare and contrast the different formulation and delivery strategies for the diverse and complex molecules, from SMIPs, to proteins and to RNA.

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Alain Pralong

David K. Robinson, PhD view bio | back to agenda
Deputy Director, CMC Vaccines Development and Surveillance, Bill & Melinda Gates Foundation

Advancing Global Health: The Role of Vaccine Bioprocessing and Commercialization

The introduction of vaccines ranks as one of the greatest healthcare achievements in modern history. Through the global efforts of the vaccine community, small pox has been eradicated worldwide, as has one of three wild type strains of polio. Other infectious diseases such as measles have been eliminated from large regions of the world. All of these advances have contributed to increases in health around the globe. However, continued success will depend on continued innovation. Recent technical advances include the introduction into clinical studies of new vaccine vectors such as mRNA, new methods to administer vaccine such as microneedle array patches, improvements in the thermostabilization of vaccines and the use of process intensification, continuous processing and modular facility design to improve vaccine manufacturing. Still, significant efforts are needed to see each of these advances through conceptualization and pilot studies into widespread adoption and implementation. In addition, additional investments are needed in novel designs for filling/packaging of vaccines, methods to reduce the number of injections each child must receive and improvements in the speed and reliability of vaccine manufacturing and release. The speaker will touch upon each of these topics during the presentation.

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Rahul Singhvi

Rahul Singhvi, ScD view bio | back to agenda
Chief Operating Officer, Vaccine Business Unit, Takeda Pharmaceutical Company

Vaccines: Unprecedented Opportunities for Impact

Vaccines have proven to be highly effective tools in reducing or eliminating the disease burden of many infectious diseases.Continuous innovation has resulted in the introduction of several new vaccines in the past two decades.However, several challenges remain that require a fresh look at how best to take advantage of this great technology.Key challenges include rapid introduction of effective vaccines against emerging infections, and continued focus on access and affordability of vaccines for all those who need them.These objectives must be addressed in a background of an industry facing consolidation, pricing pressure, and entry of low cost manufacturers.This presentation will provide some guiding principles to ensure that innovation in vaccines continues unhindered in an environment of escalating opportunity costs and difficult economics.

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Indresh Srivastava

Indresh Srivastava, PhD view bio | back to agenda
Site Head, Manufacturing Technology, Protein Sciences Corporation, Sanofi Pasteur

Analytical Bridging for the Process and Manufacturing Changes

The presentation will focus on the strategy for implementing process changes in the licensed vaccine.

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Martin Wisher

Martin Wisher, PhD view bio | back to agenda
Senior Regulatory Consultant, Quality & Regulatory Management, MilliporeSigma

Quality Control of Human Viral Vaccines: Reducing the Risk of Viral and Microbial Contamination

Ensuring the quality of human biological medicinal products involves the application of 3 complimentary approaches: appropriate sourcing and testing of starting materials; testing of production process intermediates and final product and validation of the upstream production and downstream. This presentation will review the current regulatory expectations for the quality control of cell banks, virus seed stocks, virus bulk harvests and final vaccine. Limitations of the present assays will be discussed and the use of new technologies: next generation sequencing and degenerative PCR for adventitious agent detected will be described.

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