# Computational Biology (Cobi) Tools as a Framework for Physiologically-Based Pharmacokinetic/Pharmacodynamic Model Extrapolation from Rabbit to Human for Ophthalmic Drug Products

> **NIH FDA U01** · CFD RESEARCH CORPORATION · 2021 · $179,978

## Abstract

Project Summary/Abstract:
Evaluating bioequivalence of ophthalmic drug products in humans is challenging for ethical and practical
reasons. Often, animal models are used to evaluate ophthalmic bioequivalence. Unfortunately, methods for
translation of animal model results to humans has proven elusive. There is a critical need to develop
computational tools to assist with interspecies translation. Physiologically-based model extrapolation can provide
a means for explaining interspecies differences in pharmacokinetics (PK) and pharmacodynamics (PD). The
objective of the proposed work is to develop a translational tool framework for capturing interspecies differences
in the PK and PD of ophthalmic drug products using physiologically-based model extrapolation methods. To
facilitate framework development, we will collect physiologically-based rabbit and human ophthalmic PK and PD
models from literature. Model components will be integrated with our existing models to create optimized models.
Our team’s experience in multiscale ophthalmic modeling enables the framework to include models of varying
complexity (compartmental, quasi-3D, 2D and novel 2.5D models), which provides are more complete picture of
potential extrapolation solutions versus implementing a single model type. Model details (i.e. modeled tissues,
segment, complexity, physiological phenomena, etc.) will be organized in a spreadsheet which will include model
capabilities and limitations. In parallel, an opensource database comparing rabbit and human anatomical and
physiological parameter values/value ranges will be created. Collected and optimized rabbit PK and PD models
will be extrapolated/scaled up to human models by changing anatomical, physiological and biophysical
parameter values. Common dosing scenarios (topical and intravitreal administration of solutions, solid
suspensions and emulsions) will be simulated using extrapolated, collected and optimized human ophthalmic
PK and PD models for comparison purposes. Comparison of simulation results will enable identification of the
current translational knowledge gaps. The framework will allow evaluation of potential solutions to closing these
knowledge gaps. This project will enhance public health by improving regulatory confidence, speed and
efficiency in the approval process for new and generic ophthalmic drug products and by decreasing costs to the
public.

## Key facts

- **NIH application ID:** 10166845
- **Project number:** 5U01FD006929-02
- **Recipient organization:** CFD RESEARCH CORPORATION
- **Principal Investigator:** Carrie German
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2021
- **Award amount:** $179,978
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166845

## Citation

> US National Institutes of Health, RePORTER application 10166845, Computational Biology (Cobi) Tools as a Framework for Physiologically-Based Pharmacokinetic/Pharmacodynamic Model Extrapolation from Rabbit to Human for Ophthalmic Drug Products (5U01FD006929-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10166845. Licensed CC0.

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