Cambridge Healthtech Instituteの第3回年次会議
Vaccine Development and Manufacturing
2023年8月14 - 15日、EDT（米国東部標準時）
Registration and Morning Coffee8:00 am
CHALLENGES & OPPORTUNITIES IN VACCINES
The Power of Public-Private Partnerships to Support Multi-Use Technologies in the Next Generation of Vaccine Development
Rachel Rath, Director, BARDA Alliance at Johnson & Johnson Innovation, JLABS
Early-stage companies and innovation leaders will discuss the advancement of multi-use technologies to support the next generation of vaccine development and how public-private partnerships can accelerate these innovative efforts.
Opportunities to Enhance Vaccine Development and Approval Process: On a Path to More Personalized Vaccinology
John Mattison, Operating Partner/Chief Medical Information Officer, Arsenal Capital Partners
Speed to market of COVID vaccines did not support commensurate predictive value of durability of those vaccines against emerging variants, nor about predicting who might suffer adverse events. How can early R&D and later clinical trials systematically and cost-effectively maintain speed to market while supporting more predictive value and durability? We need creative strategies for better T cell profiling and biobanking of specimens for subsequent focused analysis. Strategies to minimize regulatory capture and maintain international competitiveness must be considered. Matching vaccine strategies to sub-cohorts will ultimately lead to personalized vaccinology and help minimize vaccine reluctance.
Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own12:00 pm
Session Break12:30 pm
CELL LINE DEVELOPMENT & OPTIMIZATION FOR VACCINES
Development of the Filamentous Fungus Thermothelomyces heterothallica, C1, into a Next-Generation Production Platform for Human And Animal Vaccines
Mark A. Emalfarb, Founder & President & CEO, Dyadic International, Inc.
C1-cells have been shown to express antigens at > 100 times higher, in less time, without the need to remove viruses compared to baculovirus cells. C1-cells can express multicomponent vaccines, such as VLPs and ferritin nanoparticles. C1 strains have been shown to express more than 2.5 g/L (in 4-5 days), using low-cost chemically defined media in stainless-steel or single use microbial E. coli bioreactors. C1 cells lines have been used to stably express a growing number of antigens such as SARS-CoV-2 (i) Full Spike and (ii) RBD’s; H1, H5 & H7 Hemagglutinin; Neuraminidase, West Nile, Mumps, Rabies, Rift Valley Fever, etc.
Overcoming Manufacturing and Analytical Challenges to Develop a Successful Insect-Cell Expressed Protein-Based COVID-19 Vaccine
Nikolai Petrovsky, PhD, Research Director, Vaxine Pty Ltd.; Professor of Medicine, Flinders University
- Recombinant proteins remain amongst the most reliable, low cost and safe approaches to pandemic vaccine delivery
- Protein vaccines face challenges in design, manufacture, structural characterisation, and scale up
- Adjuvants are critical to protein vaccine success
- Artificial intelligence tools can dramatically accelerate the process of vaccine design and optimisation?
- Now is the time to closely examine all aspects of pandemic vaccine design, manufacture, and supply chains to see how to do it better next time
Sponsored Presentation (Opportunity Available)2:10 pm
Networking Refreshment Break2:25 pm
FORMULATION DEVELOPMENT & STABILITY OF VACCINES
Development of Virus-Like Particle (VLP) Vaccine Candidates
Trudy G. Morrison, Professor, Microbiology & Physiology System, University of Massachusetts
My laboratory has developed a novel vaccine platform, virus-like particles (VLPs), formed with the structural proteins of Newcastle disease virus (NDV), an avian paramyxovirus. Using our platform, we have constructed VLPs containing the respiratory syncytial virus (RSV) F and G glycoproteins. Our preclinical studies have shown that these VLPs are excellent vaccine candidates for protection from RSV infection of neonates by maternal immunization and the protection of the elderly.
Pre-Formulation Developability Assessments: Design and Critical Considerations
Lisa A. Kueltzo, PhD, Director, Formulation & Stability, Vaccine Production Program Lab, NIH NIAID
Developability assessments are key in making decisions on how, and indeed if, a therapeutic or vaccines candidate can move from bench to clinical trial. Yet, these assessments are only as good as we design them. It is crucial to ensure the assessment performed in any one organization includes more than a panel of analyses appropriate to the program molecules. The assessment design and implementation must also take into account program capabilities and goals, limitations, and risk tolerance. In this presentation we will discuss the elements of development assessments, their alignment with pre-formation programs, and successful incorporation into early stage development programs.
Session Break and Transition to Plenary Keynote Session3:40 pm
PLENARY KEYNOTE: SOLVING TODAY'S CHALLENGES
Overcoming the Challenges of Bioprocesses: The Future of Biomanufacturing
Glen R Bolton, PhD, Executive Director, Late Stage Bioprocess Development, Amgen Inc
Novel therapies and technologies are emerging to meet the needs of patients; however, the manufacturing of biopharmaceuticals remains a complex and challenging process. As demand for biopharmaceuticals grows, the industry faces new challenges in terms of scalability, cost, and process robustness. The implementation of innovative technologies to improve process efficiency and the importance of process control and data analytics in ensuring process robustness are key levers to meet these challenges.
Commercializing Gene Therapies - The Combined Power of Patient Advocacy and Cost-Effective Manufacturing
Rachel Salzman, DVM, Founder, The Stop ALD Foundation & Global Head, Corporate Strategy, Armatus Bio
There is only a very small handful of FDA-approved gene therapies. This presentation will examine the development of an FDA-approved gene therapy where patient advocacy played a critical role resulting in the first-ever clinical use of a lentiviral vector. Although manufacturing continues to represent a significant challenge throughout the entire R&D journey, there are opportunities for advocacy and manufacturing communities to seek alignment and combine their collective powers to achieve the common goal of increasing patient access to transformative medicines.
Welcome Reception in the Exhibit Hall with Poster Viewing5:30 pm
Close of Day6:30 pm
Registration and Morning Coffee7:30 am
DEVELOPMENT, BIOPROCESSING, AND MANUFACTURE OF VACCINES
Pre-CPE Cellular Events as Surrogate for Virus Potency Analytics - A Key for Accelerated Vaccine Development
Johanna Bacher, PhD, Junior Researcher, Biotechnology, ACIB GmbH
Vaccine production processes are continuously optimized to produce high and pure viral titers, but analytical methods to determine the infectious titer in bulk, still lag. TCID50 and plaque assay are still gold-standard virus potency assays and rely on the induction of a cytopathogenic effect (CPE) as an endpoint for evaluation. These morphological changes are usually only visible after 1-2 weeks of infection and can be replaced by cellular events induced early after virus infection like a pro-inflammatory innate immune response in the form of secreted cytokines.
Laser Force Cytology as a Process Analytical Technology (PAT) to Improve the Efficiency and Consistency of Biologics Research, Development, and Production
Colin G. Hebert, PhD, Senior Vice President, Scientific and Business Operations, LumaCyte
The development and production of vaccines & cell and gene therapies can be challenging and time-consuming due to the complex nature of the raw materials, process and final product. Many current analytical methods, especially for viral vectors and vaccines, face challenges in terms of speed, reproducibility, and resource requirements. Here we present the application of laser force cytology as a real-time PAT to rapidly characterize viral infectivity and other critical quality attributes (CQAs) within minutes to inform and optimize the production process as well as its application for offline release and potency assays used to ensure product quality and consistency.
Development and Optimization of a New Process to Maximize the Yield of Recombinant Hemagglutinin Production, a Component of Flublok Influenza Vaccine
Jamal Meghrous, PhD, Senior Scientist, Cell Culture & Production, Sanofi
Sanofi’s influenza vaccine is the only recombinant influenza vaccine approved by the US Food and Drug Administration (FDA) and by the European Medicines Agency. Successful commercialization of influenza vaccines is a key growth driver for Sanofi Pasteur to increase the yield, decrease the cost per dose, and increase Manufacturing (MFG) capacity. We developed a new Fed-Batch process for production of recombinant HAs that results in 80% increase in rHA yield compared to the current production process.
Coffee Break in the Exhibit Hall with Poster Viewing10:00 am
Breakout discussions provide an opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges. Please visit the breakout discussions page on the conference website for a complete listing of topics and descriptions.
DEVELOPMENT, BIOPROCESSING, AND MANUFACTURE OF VACCINES (CONT.)
A Recombinant Influenza Vaccine Made from Membrane Vesicles
Christopher P. Locher, PhD, Co-Founder & CEO, Biology, Versatope Therapeutics
We have found that bacterial extracellular nano-vesicles (bEVs) may be useful as a strong adjuvant and displays the M2e antigen as an ion channel, thereby perhaps configuring the antigen in its native ion channel structure on a viral-infected host cell. Since bEVs co-express a lipopolysaccharide (LPS), we have improved the safety and tolerance of the nano-vesicles by creating a genetically-modified cell line that does not induce high levels of pyrogenicity. We found that a bEV-expressing M2e protects against fatal H5N1 infection in ferrets as well as mice at nano-gram doses with two immunizations.
Revisiting Membrane Chromatography and Absorbers Viral Vaccine Purification
Alois Jungbauer, PhD, Professor & Head, Biotechnology, Institute of Bioprocess Science and Engineering, University of Natural Resources and Life Sciences (BOKU)
- A lot of choices of membrane absorbers and fiber materials for virus purification compared to the past
- What is the selection criterion for a membrane adsorber and fiber material
- The ideal separation process for a viral vaccine
Sponsored Presentation (Opportunity Available)12:30 pm
Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own1:00 pm
Refreshment Break in the Exhibit Hall with Poster Viewing1:30 pm
ANALYTICAL TOOLS AND CHARACTERIZATION STRATEGIES FOR VACCINES
Advances in Quality Control Standards for Polysaccharide Conjugate Vaccines
John Cipollo, PhD, Senior Principal Scientist and Team Lead, USP
Polysaccharide Conjugate vaccines are the most successful preventatives against bacterial disease and are composed of defined polysaccharides individually conjugated to carrier protein. This presentation will provide an update on standards and tools to support vaccine quality from raw materials through release testing. The recent revisions to General Chapter <198>, focused on NMR for bacterial polysaccharide for identity, and reference materials to support testing of quality attributes will be discussed.
Characterization Methods for Vaccines
Marina Kirkitadze, PhD, Head Bioprocess Support & PAT Platform, Analytical Sciences, Sanofi Pasteur
The topic of the presentation is a physico-chemical characterization of vaccine products. Several methods used to measure product attributes at different stages of manufacturing will be discussed. The output can be used for process monitoring, product characterization, and potentially for real-time release.
Single-Particle Imaging to Quantitate Biophysical Properties of mRNA Lipid Nanoparticles and Engineer Improved Vaccines
Sabrina Leslie, PhD, Associate Professor, Physics and Astronomy Department, The University of British Columbia
We present a quantitative single-particle imaging platform that enables simultaneous measurements of the size, mRNA-payload, and dynamic properties of vaccines in cell-like conditions. We investigate the dependence of mRNA-lipid-nanoparticle structure and fusion dynamics on formulation, using commercially available formulations as a starting point. These measurements are made on confined, freely diffusing particles, and during reagent-exchange such as in response to solution pH, in order to emulate intracellular dynamics in a controlled setting. Over the long term and in collaboration with health scientists, we propose to correlate multi-scale data sets including single-particle measurements made in vitro as well as in cells and tissues, with clinical results, to create a throughline of understanding of vaccine effectiveness from the microscopic to clinical scale, to enable and optimize their rational design and engineering.
Refreshment Break in the Exhibit Hall with Poster Viewing3:45 pm
Size Characterization of Vaccine Antigens: Ensemble vs. Single Particle Analysis Approach
Rahul Misra, PhD, Scientist, Biophysics and Process Analytical Technology, Sanofi
Light scattering techniques (DLS) for protein size characterization takes an ensemble-based approach to particle sizing. Although being a gold standard, this approach may not accurately distinguish particle sizes in a multimodal sample where the diameter of particles is similar or when particle size distributions are broad. Additionally, concentration of large particles can be overestimated thereby skewing the particle size distribution of the sample. On the other hand, single particle analysis approach involves tunable resistive pulse sensing (TRPS) technology which measures the size of individual particles passing through a nanopore and claims to provide more accurate particle size distribution data within a sample. Particle concentration analysis is also based on single-particle measurements thereby ensuring highly accurate calculations for each size band compared to the ensemble-based approach. The present study performs the comparative analysis of size distribution of vaccine antigens to evaluate the performance of these methods.
Microfluidic Electrophoresis-Based Detection and Characterization of dsRNA Contaminants in mRNA Vaccines
Adriana Coll De Pena, Graduate Student, Biomedical Engineering, Tripathi Lab, Brown University
Despite the recent groundbreaking advancements in mRNA vaccine development, analytical methods have not evolved at the same rate, leaving a significant need for highly sensitive and rapid purity assessment methods. Here, we propose a dual dynamic staining high-throughput microfluidic electrophoresis analytical method for the detection and characterization of dsRNA contaminants in mRNA vaccines. With an mRNA maximum loading capacity of 13 ng/μL, we can detect dsRNA contaminants as low as 0.1-0.6% of the total concentration.
Close of Vaccine Development and Manufacturing Conference5:30 pm