4:00-5:00 Problem Solving Breakout Discussions
Concurrent problem solving breakout discussions, open to all attendees, speakers, sponsors, and exhibitors, provide a forum for discussing key issues and meeting potential collaborators. Plan to take part and explore these topics in-depth. Please pick a topic of your choice, find your table and join in.
Practical Application of Immunogenicity Pre-Clinical Risk Assessment
Moderators: Amy S. Rosenberg, M.D., Director, Division of Therapeutic Proteins, Office of Biotechnology Products, FDA; Paul Chamberlain, NDA Advisory Board
• Pertinent risk factors
• Features of a good risk analysis and risk mitigation plan
• Sharing of experiences of applying risk assessment in pre-clinical and clinical studies
• How should we interpret bioanalytical signals relative to clinical significance?
• Sharing experiences in presenting an immunogenicity risk assessment to the regulatory authorities.
• Risk mitigation: when is immune tolerance induction indicated?
Relevance of Animal Models for Predicting the Immunogenicity of Therapeutic Proteins
Moderator: Jack Ragheb, M.D. Ph.D., Principal Investigator, Immunology, Therapeutic proteins, CDER/FDA
• Are relative immune responses (aggregated vs. non-aggregated human protein in a mouse) a valid measure?
• How might known differences in the human and mouse adaptive and innate immune systems impact the results?
• What, if any, is the role of adjuvants in such studies?
Product-Related Factors that Contribute to Immunogenicity
Moderator: Wim Jiskoot, Professor, Drug Delivery Technology, University of Leiden (wants a co-host)
• Which structural variants increase immunogenicity?
• How SVPs may impact immunogenicity, safety and efficacy
• Comments on impact of formulation on SVPs and immunogenicity
• Relation between formulation, dosing , packaging and immunogenicity
• Measures to ensure long-term stability and avoid aggregation in protein drug products
Immune Tolerance Approaches
Moderator: Alexandra Joseph, Ph.D., Associate Scientific Director. Investigative Clinical Immunology, Genzyme, a Sanofi Company
• Factors that promote tolerance / promote immunogenicity
• Impact of the dosing regimen on drug immunogenicity
• Impact of formulation and formulation change on immunogenicity
• Design of therapeutics for reduced immunogenicity
Predictive Tools for Immunogenicity
Moderator: Theresa J. Goletz, Ph.D., Director, Medical Sciences Clinical Immunology, Amgen, Inc.
• How predictive are the methods to analyze T cell epitopes?
• Pros and cons of in silico, in vitro and in vivo methods.
• Engineering to avoid immunogenicity
Dealing with Pre-existing Positive ADA Activity in Study Patients
Moderator: Boris Gorovits, Ph.D., Director, Pharmacokinetics Pharmacodynamics & Metabolism, Pfizer, Inc.
• Prediction of reactivity in naive samples vs. reactivity in pre-dose samples collected from study patients
• If pre-dose samples with high levels of reactivity are identified, should we care? If so, what are the appropriate follow up activities?
• Open exchange - what have you seen when characterizing pre-existing ADA and their impact?
• What are the regulatory expectations for characterizing pre-existing ADA?
Challenges in Developing Neutralizing Antibody Assays
Moderator: Jaya Goyal, Ph.D., Principal Investigator, Translational Medicine, Biogen Idec, Inc.
• Factors for selection of cell-based NAb vs. non-cell-based NAb assays
• Bioanalytical challenges
• Challenges for NAb validation
• Interpretation of the results and implications for risk assessment