Strategies for Effective Neutralizing Cell Based Assays in Early Immunogenicity Risk Assessment

Traditionally, small molecules have dominated the pharmaceutical market. These chemical entities have helped to improve dramatically the quality of life by treating a broad range of diseases and illnesses. The past decade has witnessed a remarkable increase in large molecule, antibody-based therapies. It is forecasted that by 2016 the dominance of small molecules will have been replaced by more complex, protein drugs or biologics. Biologics are a class of drugs of growing importance because they offer unique modes of action with far fewer side effects but they are expensive to develop and to bring to the market.

One potential obstacle impacting drug development is the occurrence of anti-drug antibodies generated by the immune response of the patients receiving such drug. These anti-drug antibodies that bind to the drug have the potential to neutralize its activity in treated patients. Neutralizing antibodies (NAbs) can impact the efficacy and safety of the drug depending on patient-related and product-related factors. In addition, there are instances where neutralizing antibodies have caused infusion reactions and deficiency syndromes. The FDA provides guidance pertaining to immunogenicity risk management for biologics including risk assessment and mitigation, and neutralizing antibodies detection and assay selection.

Neutralizing antibodies assays are secondary characterization assays designed to determine whether anti-drug antibodies specifically neutralize drug activity. Two types of assays have been used to measure neutralizing antibodies: cell-based biologic assays and non-cell based ligand binding assays. The FDA recommends that cell-based biologic assays be used when possible since these are considered to be more reflective of the in vivo situation. The neutralizing antibodies assay should also be reflective of the drugs mechanism of action. Thus, neutralizing antibodies detection is important in interpreting the therapeutics’ efficacy and safety in vivo.

This webinar will discuss the challenges and the importance of neutralizing antibodies assays and a well thought out immunogenicity strategy in drug development to assess and mitigate risk.

Speaker

Paul W. Rhyne, Ph.D., Scientific Director, Q2 Solutions, a Quintiles Quest Joint Venture

Dr. Rhyne, currently leads a bioanalytical group for Q2 Solutions, a Quintiles Quest joint venture. Dr. Rhyne has more than 15 years of scientific leadership experience in laboratory operations, clinical biomarkers, large molecule PK analysis, and Immunogenicity assessment. He obtained his Ph.D. at the University of Tennessee Memphis and completed 3 years of post-doctoral studies at St. Jude Children’s Research Hospital.
Dr. Rhyne was an Associate Director at Bristol-Myers Squibb Company, a Senior Director at Tandem laboratories, and has held many senior leadership positions at Upstate Biotechnology and Amplistar Inc. A noted industry expert in clinical biomarkers and large molecule bioanalytical analysis, and has published many scientific publications in peer reviewed journals. Dr. Rhyne is an active member of the American Association of Pharmaceutical Scientists including serving on programming committees, steering committee for translational biomarker focus group, and chair of the biomarker discussion group.

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