How Certara MIDD Experts Overcame Client Regulatory Challenges

Director, Clinical Pharmacologist, Certara

In late 2023, a U.S. client turned to Certara after the FDA raised concerns about their dose selection strategy. We conducted an Optimus gap analysis, recommended additional dose cohorts for their First-in-Human study, and proposed an improved design for dose optimization.

Subsequently, the FDA and EMA approved the updated plan, and the study was filed just 2.5 weeks after the final FDA meeting. Certara’s strategic approach successfully brought the client’s program back on track.

Director, Early Development, Certara

A client developing novel antibody-drug conjugates faced challenges with overly conservative starting doses in dose-escalation trials, often 20-fold lower than effective doses. Certara’s preclinical, clinical pharmacology, and model-informed drug development experts collaborated to identify the root cause: the non-linear pharmacokinetics (PK) of ADCs and antibodies.

Our team proposed basing the starting dose on monkey-based allometric PK predictions and incorporating preclinical efficacy data via PK/PD modeling. By basing the starting dose on exposure rather than preclinical toxic doses the client was able to avoid multiple unnecessary, ineffective levels while maintaining safety, accelerating patient access to potential benefits.

VP, Head of DMPK-Drug Development Science, Certara

Following a pre-investigational new drug application (pre-IND) meeting, a client in the nonclinical drug discovery space urgently needed support to address the Agency’s request to initiate clinical development in patients versus the initial proposal of conducting the first-in-man study in healthy volunteers.

The Certara DMPK team provided an independent review of the available DMPK data to identify gaps in the nonclinical PK package, provided de-risking recommendations, and supported the design and execution of additional in vitro drug interaction (DDI) studies to enable the planned Phase 1 trial. Our experts also supported the IND submission, and the client didn’t receive any additional nonclinical PK comments from the Agency. The clinical Phase 1 trial was initiated in a timely fashion.