AAPS 2025 PharmSci 360

Abstract: PBPK modeling provides a mechanistic framework to address key questions throughout drug development while reducing reliance on extensive in vivo or even animal studies. PBPK modeling is particularly valuable for dermal and ocular delivery routes of administration. These applications involve unique physiological barriers, exposure considerations, and complex formulation-dependent processes that benefit from a mechanistic approach.

This presentation highlights two PBPK models:

1. A mechanistic dermal absorption model that enables a bottom-up approach for dermal absorption to predict local and systemic compound exposures. The model supports in vitro in vivo extrapolation (IVIVE), informs experimental design, and incorporates dynamic re-parameterization of formulation characteristics to capture metamorphic processes critical for topical products.

2. A mechanistic ocular model developed to addresses challenges in predicting drug disposition in the eye, where diseases such as glaucoma and macular degeneration, as well as off-target toxic effects of systemic therapeutics, demand precise assessment of exposure within the different parts of the eye. To simulate the particular complexities of the eye, the model integrates finite element methods, anterior chamber convection, melanin binding, and intravitreal injection geometries. Here we provide verification studies against rabbit and human data for topical, intravitreal, oral, and IV administration routes that demonstrate its utility in supporting ocular drug development.

Presenters:
Bryan Holland, PhD, Senior Research Scientist at Certara
Daniel Paterson, PhD, Research Scientist II at Certara

Abstract: Early planning for anti-drug antibody (ADA) assessment is essential to the successful development of biologic therapies. This presentation will highlight the importance of a phase-appropriate ADA assay strategy, show how proactive immunogenicity planning can support regulatory compliance and risk mitigation, while also enabling meaningful interpretation of translational pharmacokinetic and pharmacodynamic data to inform clinical decision-making. Attendees will gain practical insights into ADA assay design across development stages – from preclinical through to BLA submission. The presentation will also explore how to address the impact of ADA in translational and early development – illustrated through real-world case studies that demonstrate the benefits of early ADA considerations.

Presenters:
Ha Bruno, PhD, Associate Director, Chemistry, Manufacturing & Controls at Certara
Elliott Offman, BSc Pharm, MSc, PhD, Vice President, Clinical Pharmacology & Translational Medicine at Certara

Presenter: Armin Sepp, PhD, Senior Principal Scientist at Certara

Presenter: David B. Turner, PhD, Senior Scientific Advisor and Head of Mechanistic Oral Absorption Modeling, Certara

Presenting author: Dan Paterson, PhD, Research Scientist at Certara

Presenting author: Dan Paterson, PhD, Research Scientist at Certara

Presenting author: Bryan W. Holland, PhD, Senior Research Scientist at Certara

Presenting author: Dan Paterson, PhD, Research Scientist at Certara