Back to: BsUFA III Regulatory Science Pilot Program: Progress Update
Presenters
Jeffry Florian, PhD
Associate Director
Division of Applied Regulatory Science (DARS)
Office of Clinical Pharmacology (OCP)
Office of Translational Sciences (OTS)
Center for Drug Evaluation and Research (CDER)
US Food and Drug Administration (FDA)
Kristina Howard, DVM, PhD
Research Veterinary Medical Officer
Division of Applied Regulatory Science (DARS)
Office of Clinical Pharmacology (OCP)
Office of Translational Sciences (OTS)
Center for Drug Evaluation and Research (CDER)
US Food and Drug Administration (FDA)
Abstract
This presentation provides updates on two BsUFA Regulatory Science Program projects. The first project, presented by Jeffry Florian, conducts a landscape assessment of approved biosimilar submissions, retrospectively analyzing comparative analytical data, PK similarity, efficacy, and safety studies for Adalimumab and Trastuzumab biosimilars. The analysis reveals that while differences in quality attributes are sometimes observed, these are typically resolved with additional analytical data or PK similarity results and do not preclude a determination of similarity. PK similarity studies consistently meet pre-specified criteria, with initial issues often resolved by increasing sample size due to variability. Comparative clinical efficacy studies demonstrate similar outcomes but do not appear necessary to resolve residual uncertainties from analytical or PK assessments. The conclusion is that comparative analytical and PK studies are generally sufficient to demonstrate high similarity. The second project, presented by Kristina Howard, explores alternative methods for assessing biosimilar immunogenicity to potentially replace clinical studies. Data mining of biosimilar applications shows sponsors submit in vitro immunogenicity assay data, but there is significant variability in methods and interpretation is difficult, suggesting a need for standardization. Research using a humanized BLT mouse model indicates these mice can produce measurable immune responses and anti-drug antibodies to biological products, suggesting potential for informing immunogenicity assessment. Sponsors are encouraged to submit in vitro data to help advance these alternative approaches.