First-in-Human (FIH) Dose Predictions

PBPK modeling can be applied for the purpose of PK and dose prediction across drug discovery and development from the early stages prior to lead development where limited data is available. This approach enables greater understanding of the effect of physiological variables or disease status on PK. A FIH PK prediction uses readily available physiochemical, in vitro and preclinical in vivo input data. We can also include early drug-drug interactions (DDIs) prediction and formulation comparisons.

Accurate FIH dose predictions for biologics such as monoclonal antibodies, therapeutic proteins, and bi-/multi-specifics requires consideration of various features that determine the clinical PK properties of such modalities, including target-mediated drug disposition (TMDD) and immunogenicity (IG) caused by anti-drug antibodies (ADAs). Certara’s QSP services group as well as its Immunogenicity Simulator was designed to efficiently account for these complex mechanisms to enable a robust FIH dose prediction based on readily available preclinical input data. This approach integrates preclinical mechanistic evidence and physiological system models to investigate and predict human PK of biotherapeutics.

Certara’s clinical pharmacology team’s expertise is instrumental in designing and executing FIH studies to help assess an investigational drug’s safety, tolerability, and pharmacokinetics in humans. Our team assists with strategic FIH protocol development, preparing for pre-IND meetings, and navigating regulatory interactions during IND/CTA reviews. The Investigational New Drug (IND) or Clinical Trial Application (CTA) review process can present a maze of inquiries and requests from global regulatory bodies and our teams streamline communication and ensure that responses are clear, data-driven, and aligned with regulatory expectations.