Day 1 | Day 2 | Day 3
WEDNESDAY, OCTOBER 28
7:30am – 8:30am Registration for Conference B
8:30 Chairperson’s Remarks
8:35 Featured Presentation
A Regulatory Perspective on Protein Therapeutics
Susan Kirshner, Associate Chief, Laboratory of Immunology, Office of Biotechnology, FDA
Immunogenicity is a significant safety and efficacy concern for protein therapeutics. This talk will provide a regulatory perspective on the immunogenicity of biological therapeutics including: FDA expectations regarding the submission of assay development and validation data; clinical assessment of immunogenicity; managing immunogenicity and immunogenicity studies as part of comparability exercises. Common pitfalls in submissions will be discussed.
9:05 FDA Expectations for Immunogenicity Assessment: Is the Target Moving?
Steve Keller, Ph.D., Director, Bioanalytical Sciences, Pre-clinical and Clinical Development, Facet Biotech Inc.
In contrast to other bioanalytical methodology, immunogenicity assays lack ideal positive controls, suffer from imperfect cutpoints, often rely on specialized reagents making standardization impossible, and ultimately end with a method for identifying neutralizing antibodies that present a myriad of challenges. To provide some consistency, a number of white papers have been published. Using these, you can be armed with the right assays, validated in a manner consistent with industry best practices, and including the right sampling time points. But does the FDA want more? This talk will summarize interaction with the FDA related to immunogenicity for a Ph1 oncology therapeutic antibody.
9:35 Sponsored Presentation (Opportunity available, please
contact Ilana Quigley, iquigley@healthtech.com)
9:55 Networking Coffee Break, Poster and Exhibit Viewing
10:30 KEYNOTE
Priorities for EU Guidance on Immunogenicity Risk Assessment for Therapeutic Monoclonal Antibodies
Paul Chamberlain, NDA Advisory Board
New EU guidance is currently in preparation to assist sponsors in developing an appropriate strategy for managing immunogenicity-related risks for monoclonal antibodies. This presentation will consider how the accumulated clinical experience for this of product might be interpreted to identify the priorities for the regulatory approach. This will include selection of bioanalytical methods and presentation of clinical data to regulatory agencies.
11:00 Panel Discussion with the Speakers
11:30 Impact of Formulation and Drug Product Features on Immunogenicity of Proteins
Joël Richard, Ph.D., Senior Director, Head, Drug Product Development, Pharmaceutical Development, IPSEN - Beaufour Ipsen Industrie
The various reasons why a protein-based drug product (DP) can induce immunogenicity will be presented. Excipient-induced and aggregate-induced immunogenicity will be reviewed, and the main features of aggregates inducing immunogenicity will be discussed. The effect of formulation parameters on aggregate-induced immunogenicity will be presented, as well as the most efficient methods to detect and quantify aggregation in a protein formulation. The case of immunogenicity induced by impurities appearing during DP processing (interactions with fill-and-finish equipments), storage and transport will also be addressed. A case study based on a formulation change will emphasize the key role of excipients and protein interactions with containers and closures (leachables and extractables).
12:00pm Focus on Sub-visible Aggregates and their Impact on Immunogenicity
Jack A. Ragheb, M.D., Ph.D., Principal Investigator, Laboratory of Immunology, Division of Therapeutic Proteins, OBP, CDER, FDA. (Tentative.)
It is well established that large protein aggregates are produced during the pharmaceutical manufacturing of therapeutic protein products and that these can enhance immunogenicity. In turn, the patients’ immune response can compromise the efficacy and safety of the therapeutic protein. This talk will focus on 0.2-10 μm subvisible protein aggregates, how they may interact with the immune system, the potential impact these particles may have on a product’s safety and efficacy profile, the factors affecting this risk, and recent efforts to evaluate and control the associated risk.
12:30 End of Immunogenicity Assessment and Clinical Relevance Lunch on Your Own for Conference B Attendees