Conference Report: Immunogenicity: Prediction, Detection and Effective Assay Development

Abstract

The Immunogenicity: Prediction, Detection and Effective Assay Development conference, organized by the Pharma iQ, a division of IQPC, was held in Munich, Germany, 21–23 June of 2010. The meeting covered a broad range of topics related to the unwanted immunogenicity of biotherapeutics. Perspectives from the US FDA and EMA were presented along with discussions focusing on analytical method development and validation, methodologies allowing for prediction of potential immunogenicity, risk-based assessment and mitigation of immunogenic potential of biologics, and other topics. The conference consisted of a preconference workshop and 2 days of plenary sessions, which included presentations as well as group discussions. Particular attention was drawn to the review of the FDA guidance and Committee for Medicinal Products for Human Use guidelines on immunogenicity evaluation. Presenters and meeting participants engaged in an active and productive discussion around scientific aspects involved in immunogenicity evaluation and methodologies involved during routine sample testing. Discussions also centered around challenges and opportunities related to detection and characterization of immunogenicity, as well as analysis of the latest technologies to enable accurate and meaningful interpretation of the results. The meeting attracted a broad range of participants from various sized companies, backgrounds and interests.

Challenges and Opportunities in Absorption, Distribution, Metabolism, and Excretion Studies of Therapeutic Biologics

“…To this end, Kumar et al described the importance of investigating the impact of aggregation on immunogenicity and potential coupling of T and B cell epitopes and aggregation-prone regions (61). Computational tools that can predict aggregation prone regions as well as T-and B-cell immune epitopes from protein sequence and structure have become available recently from several commercial vendors (58,(62)(63)(64). However, none of these tools have been thoroughly validated with in vivo human data and, therefore, the standards for prediction tools have not been established (63).…”

The Utility of Modeling and Simulation Approaches to Evaluate Immunogenicity Effect on the Therapeutic Protein Pharmacokinetics

“…While immune responses to a TP can occur in nonclinical animal species, it is often not possible to predict immunogenicity in healthy subjects and patients from animal observations (9). Hence, clinical assessment of immunogenicity in the target population and evaluation of the resulting changes in pharmacokinetics (PK) as a surrogate for pharmacodynamic variables, safety, and efficacy in the individual subject is absolutely necessary (10,11). Moreover, there is an urgent need for further research in this area given the substantial increase in the number of biological products, including biosimilars, under clinical development.…”

Methods of Protein Digestive Stability Assay - State of the Art

“…Such recognition is mediated by the T-cell antigen receptor, which delivers stimulatory intracellular signals to the T cell. Allergenic proteins per se cannot be recognized by T cells; the proteins must first be processed and then presented by specialized antigen-presenting cells (APCs) (Gorovits 2010;Huby et al 2000).…”

“…Screen positive samples are further evaluated in a confirmatory assay to verify whether the signal observed in the screening assay is a result of a specific response to the protein therapeutic treatment. Confirmed positive samples are then put into downstream methods for sequential characterization based on the comprehensive consideration of immunogenicity risk assessment and mechanism of action for the protein therapeutic (Gorovits 2010;Peng et al 2011). …”