SC1: Mechanism of Action and Risk-Based Approach for Developing Neutralizing Ab Assays
MONDAY, OCTOBER 22 | 10:00 AM - 1:00 PM
Instructors: Jim McNally, PhD, Senior Director, Therapeutic Area Lead, Non-Clinical Development, Shire
Weifeng Xu, PhD, Senior Research Investigator, Bioanalytical Science, Bristol-Myers Squibb
The development of neutralizing antibody assays is a daunting task that is complicated by the specific nature of each biotherapeutic. Many factors must be assessed to choose the proper assay format, to develop a robust assay and for working out when to
invest in the development and implementation of these assays. This short course will focus on these topics and provide examples of current industry practices and publications. Specific focus will be given to a mechanism of action-based approach to
selecting the assay format. Relevant case studies will be provided.
Topics covered include:
- Current regulatory guidance
- NAb assay strategy – Immunogenicity risk assessment
- Assay format selection – Mechanism of action based approach
- Validation and implementation of NAb assays
- Case studies
Speaker Biographies
Jim McNally, PhD, Senior Director, Therapeutic Area Lead, Non-Clinical Development, Shire
Jim McNally is a QPD Program Representative, Head of Clinical Bioanalytics, and Immunogenicity Expert. In this role, he responsible for the immunogenicity strategy, bioanalytical support and scientific oversight of outsourcing of large molecule programs for EMD Serono. Previously, he was the lead of the Clinical Assay Development, Validation and Testing bioanalytical group at Pfizer based in Andover, MA. The group was responsible primarily for developing assays to support pharmacokinetic and immunogenicity analysis of the Pfizer large molecule portfolio. Prior to joining Pfizer in 2010, Jim held similar roles in the Clinical Lab Sciences group at Genzyme and Immunobiology group at Repligen. A graduate of the Microbiology and Virology Ph.D. program at LSU Medical Center in 1998, Jim has a special interest in immunomodulation and immunogenicity of biotherapeutics.
Weifeng Xu, PhD, Senior Research Investigator, Bioanalytical Science, Bristol-Myers Squibb
Weifeng had rich experience in human immunology focusing on the interaction of different immune and non-immune cells. He was recruited to BMS on 2011 as the first dedicated person to develop cell-based neutralizing Ab assay, which is critical to characterize whether the anti-drug antibody developed by clinical patient can neutralize/reduce drug efficacy. This is challenging, since the cells used in the assay needs to be closely related to the Mechanism of Action of the drug, in addition, both patient serum factors and injected drug can interfere with the assay, as Weifeng will discuss later. So far Weifeng has developed and validated multiple cell-based NAb assays for some of the most important pipeline at BMS. Along the way, Weifeng fully utilized his knowledge and critical thinking to overcome the challenging in the field, for example, how residual/carry-over human mAb therapeutics can be measured after ADA extraction and more recently, the alternative ways to overcome drug interference other than acid-dissociation.