Signal Management In Drug And Biosimilars Development

By Jacinta Aniagolu-Johnson, Phd, MSc. Senior Director, Safety and Risk Management

Signal management in drug development has been ongoing, evolving, and improving for many years. For the European Medicines Agency (EMA), Food and Drug Administration (FDA) and other regulatory bodies immunogenicity is a major area of safety concern for biosimilars as well as for peptide, protein, and drug therapeutics, all of which have the potential to trigger some level of antibody response. Hence, there is the regulatory requirement to conduct immunogenicity testing and safety assessment during pre-clinical and clinical studies, and post-approval; thereafter, usually requiring continued pharmacovigilance monitoring of immunogenicity. During pre-clinical and clinical studies, the critical focus is to decipher the potential for immunotoxicity and allergenicity, supported by appropriate data collection in order to evaluate impact of the presence of Anti-Drug Antibody (ADA) on pharmacokinetics, pharmacodynamics, efficacy, and safety. While a target focus is to ensure comparable immunogenicity, a biosimilar product with lower immunogenicity than its innovator reference product would not be excluded for biosimilarity approval. As most biosimilars are intended for long-term use to treat chronic diseases, monitoring of safety concerns beyond clinical development will continue to be equally crucial. Therefore, even though pre-clinical and clinical trials are indispensable for determining identified and potential immunogenicity risks, not all such risks (especially risks that are rare) can be identified during pre-market phase, and as such, customized risk management, pharmacovigilance, and post market commitments such as Post Authorization Safety Studies (PASS) will continue to be essential^.