Vaccine Quality throughout the Life Cycle
Managing the interface between process change implementation,
analytical characterization and regulatory strategy
August 13-14, 2012
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TUESDAY, AUGUST 14
8:00 am Morning Coffee
8:25 Chairperson’s Remarks
Albert Price, Ph.D., Technical Director, Process Development, Protein Sciences Corporation
» Keynote Presentation:
8:30 Regulatory Considerations for Implementing Process Changes
Norman W. Baylor, Ph.D., President and CEO, Biologics Consulting Group, Inc. - Biography
Vaccine development and commercialization are complex processes. The overall goal of successfully manufacturing a vaccine is to develop a process that ensures that every dose of vaccine is manufactured in a consistent manner to ensure the safety and effectiveness of the vaccine, regardless of the technology used to make the vaccine. While today’s vaccines are safe and effective, there are opportunities to apply new technologies for improving vaccine effectiveness through process changes, as well as use of novel adjuvants and delivery systems. Process modifications must meet regulatory expectations and requirements. Moreover, stringent regulatory prerequisites must be achieved throughout development for a vaccine to be considered for licensure. In this presentation I will present the regulatory challenges and risks that must be considered in implementing process changes.
9:00 Mature Product Challenges: A Case Study in “Keeping the Wheels from Coming Off!”
Michael Dekleva, Ph.D., Senior Director, Vaccine Regulatory Affairs, Merck & Co., Inc. - Biography
As in-line products mature it is often necessary to upgrade facilities, change raw materials and reagents, and investigate the impact of new and often unexpected information from the field. With regard to the latter, this talk reviews a case study involving RotaTeq®, which became the subject of an investigation to determine the presence or absence of a newly identified adventitious agent, porcine circovirus. Particular attention will be given to the regulatory complexities surrounding the investigation, and efforts to ensure the continued safety of the product, thereby addressing global agency concerns.
9:30 Immune Endpoints to Evaluate Vaccine Effectiveness for Licensing
Cara Fiore, Ph.D., Microbiologist and Regulatory Scientist, Vaccines & Related Products Applications, CBER/FDA - Biography
The US Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Vaccines Research and Review (OVRR) evaluates the safety and efficacy of vaccines in the U.S. when used for therapeutic and vaccine preventable diseases. Although clinical endpoints are the gold standard for the measure of efficacy, serological assays are often used as correlates of protection to clinically evaluate efficacy of a vaccine when disease cannot be measured. The development and validation of these serologic assays presents numerous challenges for vaccine developers and regulators alike. This presentation will use the meningococcal serum bactericidal activity (SBA) assay and the pneumococcal opsonophagocytic assay (OPA) as case studies for the importance of the development and standardization of serologic assay validation.
10:00 Coffee Break with Poster & Exhibit Viewing
10:45 USP Chapters on Biological Assays
Timothy Schofield, M.A., Head, Nonclinical Statistics Services, Arlenda Inc.; Co-Chair, Statistics Expert Committee, USP - Biography
Biological assay are used to measure the potency of vaccine products. USP chapter <111> Analysis of Biological Assays, was written in 1956, and remained undisturbed for decades. Rising to the challenge of refreshing <111>, statisticians and biological scientists empanelled by the USP have transformed that chapter into a suite of interrelated chapters, with discrete but connected emphases on bioassay design, analysis, and validation. Publication in National Formulary is planned for 2Q2012. This talk will overview the chapters with particular note of the biological and statistical considerations in assuring the reliability of vaccine potency measurement.
11:15 Initial and Ongoing Characterization of a Vaccine during Clinical Development
Jane Halpern, Ph.D., Vice President, Regulatory Affairs, Novavax, Inc. - Biography
Novavax is developing a vaccine against the respiratory syncytial virus (RSV) based upon the F fusion glycoprotein. This vaccine candidate has demonstrated promising safety and efficacy in a Phase 1 trial. The recombinant F protein antigen is produced in Sf9 insect cells and is purified as trimers that resemble the native protein. These trimers further assemble to form higher order structures (nanoparticles). The technical and regulatory challenges associated with developing methods for characterization, release, and stability for this vaccine will be described.
11:45 Characterization and Purity of a Peptide Conjugated Qbeta Virus Like Particle (VLP) Vaccine
John Amery, Ph.D., Senior Principal Scientist, Analytical Research and Development, Pfizer BioTherapeutics Pharmaceutical Sciences
Qbeta phage capsid protein is recombinantly expressed in E. coli to produce a Virus Like Particle (VLP) used as an antigen carrier for vaccines. Pfizer has manufactured Qbeta VLP and conjugated peptides to the VLP to support planned clinical programs. The consistency and purity of the unconjugated VLP and conjugated VLP have been evaluated and the impact of specific attributes on the immunogenicity of the peptide conjugated VLP has been investigated.
12:15 pm Luncheon Presentation: Label-free Analysis of Influenza Vaccine Concentration using Biacore T200
Michael Murphy, Ph.D., Biacore Application Scientist, GE Healthcare Life Sciences
Biacore biosensor technology is used for the quantitation of virus haemagglutinin (HA) in influenza vaccines. Accurate quantitation of influenza virus is achieved using an inhibition assay. The Biacore method shows higher sensitivity, precision, and recovery as compared to single-radial immunodiffusion (SRID) which is the common method used today. In addition, the analysis time is shorter. Assays performed on Biacore systems have the potential to significantly improve vaccine development and manufacturing.
1:40 Chairperson’s Remarks
Michael Dekleva, Ph.D., Senior Director, Vaccine Regulatory Affairs, Merck & Co., Inc.
1:45 Measures to Maintain the Quality of the Product over a Long Life-Cycle
Kimberly Duffy, Director, Global Vaccines, CMC Merck & Co., Inc. - Biography
This talk outlines our endeavors with large scale commercial vaccines regarding the seeds, the stability program and the analytical program. I will describe how we establish reference standards for potency assays as well as analytical tools to evaluate changes over the life-cycle. I will also describe our experiences with handling minor and major changes in the production process across multiple sites during the life cycle.
2:15 Biophysical Tools Used to Characterize Monomers, Oligomers and Particulates for Protein and Viral Vaccines
Marina Kirkitadze, Ph.D., M.B.A., Deputy Director, Head, Biophysics & Conformation Unit, Biochemistry Platform, Analytical R&D, sanofi pasteur - Biography
Understanding the mechanisms of oligomer and particulate formation in the protein and viral vaccines is an essential step for the selection of purification conditions and stable formulations to decrease product loss. A combination of light scattering and hydrodynamic methods were applied to monitor the size and molecular weight distribution of vaccine components at various stages of vaccine manufacturing that includes purified bulk concentrate and formulated vaccine product. The application of DLS, AUC, and SEC-MALS are discussed in the context of three case studies.
2:45 Biophysical Characterization of Vaccines in Context to Process Optimization and Scale Up
Indresh K. Srivastava Ph.D., Senior Director, Protein Sciences Corporation- Biography
Several state-of-the-art analytical tools are available for the characterization of vaccines such as Circular Dichroism (CD) Spectral Analysis, Tryptophanyl Fluorescence Emission Spectroscopy, Differential Scanning Calorimetric (DSC) Analysis, Fourier Transform Infrared Spectroscopy (FTIR), Capillary Electrophoresis (CE), and high resolution Mass Spectrometric Analysis. I will discuss how the information obtained from these analyses may help in process optimization and scale up.
3:15 Refreshment Break with Poster and Exhibit Viewing
4:00 QBD Principles in Assay Development and Control: Case Studies
Jian He, Ph.D., Senior Research Chemist, Vaccine Analytical Development, Merck & Co., Inc. - Biography
Quality by Design is a systematic process to build quality into the product from inception to final output. To build quality into our product, analytical assays, our Vaccine Analytical Development Department has been working on implementing QbD tools into analytical assay development, optimization, evaluation, and control. The tools we have been using are Analytical Target Profile, Risk Assessment, Design of Experiment, and Control Chart. This presentation provides case studies on the application of these tools.
4:30 Stability Studies and the Product Life Cycle: Formulation Development, Demonstrating Comparability, and Product Changes
William Egan, Ph.D., Senior Technical Expert, Novartis Vaccines and Diagnostics - Biography
This presentation will focus on the role of and changing goals of stability studies throughout the product life cycle. During product development and licensing, stability studies are targeted to establishing a consistent shelf life and set of product specifications. Following licensure, stability studies are carried out to demonstrate manufacturing and product consistency – the annual consistency studies. Following manufacturing changes, including re-formulations, stability studies are intended to either revise the product shelf life or demonstrate its consistency with the previously set value.
5:00 Vaccine Characterization, Status Quo and New Opportunities
Michele Pallaoro, Ph.D., Unit Head, Formulation Analytics, Formulation & Delivery, Novartis Vaccines & Diagnostics - Biography
Unfortunately, several hurdles reduce vaccine efficacy on some populations or toward some disease. To overcome these limitations, novel techniques to identify and improve antigens are necessary such as adjuvants, and improved delivery systems. These new approaches contribute to more potent vaccines, but novelty goes hand in hand with formulation characterization and stability of each component. I’ll describe the current status and challenges of vaccine formulation characterization with focus on Alum-based formulations and propose some of our work for vaccine formulation characterization.
5:30 End of Vaccine Quality throughout the Life Cycle
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