MI2026 – Balaji MR

Keynote Speech:
Integrating In Silico and In Vitro Immunogenicity Risk Assessment: Strategies, Assay Selection, and Regulatory Challenges

Abstract:
Immunogenicity is a critical safety concern in the development of peptide-based therapeutics, with the potential to impact both clinical efficacy and patient safety. For Abbreviated New Drug Application (ANDA) submissions, the growing complexity of peptide drugs necessitate integrated immunogenicity risk assessment to support informed decisions throughout development. In silico methodologies enable early identification of sequence- and structure based risk factors, such as major histocompatibility complex (MHC) binding potential, T cell epitope density, and population level HLA coverage. On the other hand, in vitro assay systems such as antigen presentation and T cell activation assays provide mechanistic evaluation of peptide driven adaptive immune responses, including cytokine release and T-cell activation. While in vitro assays enable functional assessment under controlled conditions, key scientific considerations include fit-for-purpose assay selection, robust study design, thorough assay validation, appropriate donor selection, ensuring biological relevance and addressing challenges associated in translating experimental findings across orthogonal approaches. An integrated framework that combines predictive modelling with functional adaptive immunity assays for immunogenicity risk assessment enables a comprehensive understanding of immune risk and supports scientifically justified risk mitigation strategies. These topics, along with practical case insights, will be presented to demonstrate strategies for streamlining study design, enhancing data interpretation, and effectively integrating immunogenicity findings into regulatory submissions.

Biography:
Dr. Balaji is a seasoned expert with over 30 years of experience in toxicology, regulatory toxicology, and toxicologic pathology, including 25 years in integrated drug discovery and development. He has led global preclinical safety strategies for new chemical entities, complex generics, and differentiated products, ensuring compliance with GLP and international regulatory standards. His contributions span end-to-end toxicology and immunogenicity risk assessment, study design, and regulatory submissions (IND, NDA, CTA, MAA), supporting successful approvals in multiple therapeutic areas. Dr. Balaji has played a pivotal role in immunogenicity evaluation for complex peptides, developing mitigation strategies and building internal capabilities. He has participated in over 15 regulatory meetings with agencies like US FDA, EMEA, and Health Canada, and was instrumental in nine successful first cycle NDA approvals. His leadership combines scientific rigor with operational excellence, driving innovation in safety evaluation and immunogenicity risk management.