ISSX 2025 International Meeting

Co-Chairs: Lei Zhang, Silver Springs, MD; Dennis Heller, Certara

Human radiolabeled mass balance studies are an important component of the clinical pharmacology programs supporting the development of new investigational drugs. These studies allow for understanding of the absorption, distribution, metabolism, and excretion (ADME) of the parent drug and metabolite(s) in the human body. Understanding the drug’s disposition as well as metabolite profiling and abundance via mass balance studies can help inform the overall drug development program. Recently, U.S. FDA published the final guidance on “Clinical Pharmacology Considerations for Human Radiolabeled Mass Balance Studies” (https://www.fda.gov/media/158178/download). This short-course will discuss the purpose and design of human mass balance study, metabolite profiling, data analysis and interpretation. When to conduct mass balance study in drug development and how the data may be used to support various decision making related to drug-drug interactions and supporting PBPK modeling will be discussed. New development and regulatory expectation and perspectives will also be provided.

• Mass balance study and metabolite profiling: Design, data analysis, and interpretation – Chandra Prakash, Agios Pharmaceuticals, USA
• Industry application and case examples – Ellen Cannady, Eli Lilly, USA
• FDA guidance on human radiolabeled mass balance studies and regulatory perspectives – Zhixia Yan Danielsen, US Food and Drug Administration, USA
• EMA’s perspectives on human mass balance studies – Karin Fawkner, Medical Products Agency, Sweden

Co-Chairs: Bhagwat Prasad, Cincinnati Children’s Hospital and Eva Berglund, Certara

This short course will focus on the role of clinical probes and biomarkers in evaluating transporter-mediated drug-drug interactions (DDIs). Attendees will gain insights into the emerging importance of transporter biomarkers in drug development, with emphasis on how they inform and confirm DDI risk of an investigational drug. The short-course will also include the selection and application of clinical drug probes to assess transporter function, study design considerations, and the interpretation of resulting data. Regulatory perspectives of biomarkers as well as exogenous probes will be discussed to highlight best practices and emerging guidelines for incorporating transporter biomarkers and drug probes into DDI risk assessments during drug development.

• Strengths and weaknesses of biomarker PBPK models to assess transporter-mediated DDIs – Hiroyuki Kusuhara, The University of Tokyo, Japan
• Endogenous probes in practice, purpose, when in drug development, study design considerations – Bridget Morse, Lilly, USA
• Clinical transporter probes: Selectivity and sensitivity​ – Xiaoyan Chu, Merck, USA
• Endogenous transporter probes from a clinical pharmacology perspective -Xinning Yang, Ellicott City, MD, USA

Co-chairs: Jaydeep Yadav, Merck; Fei Hua, Certara; Vivaswath Ayyar, GSK

Computational approaches enable in silico investigation of drug concentrations and effects that can support decision making throughout drug discovery and development. The mechanisms that drive the PK/PD, and the level of detail at which these mechanisms are understood and can be modelled quantitatively, vary across modalities, leading some modalities to be more challenging during discovery and development. This short course will introduce attendees to the key considerations and data requirements for PBPK and PK/PD modelling for challenging modalities.

• FIH dose predictions for protein degraders with PKPD modelling – Jaydeep Yadav, Merck
• Translational strategies for multi-specific antibodies (t-cell engagers) in oncology/immunology – Fei Hua, Certara
• Modelling of oligonucleotides and RNAi therapeutics – Vivaswath Ayyar, GSK

Focus Group: Modeling & Simulation

Host: Oliver Hartley, Senior Principal Scientist, Certara Simcyp