# Development and validation of a best practices framework for PBPK analysis for biopharmaceutic applications in support of model-informed biowaivers of fed state BE studies for BCS class II drugs

> **NIH FDA U01** · UNIVERSITY OF FLORIDA · 2022 · $299,965

## Abstract

PROJECT SUMMARY
Lower-cost generic drugs generated $313 billion in savings to the US healthcare system in 2019 and
approximately $2.2 trillion in the past decade. Therefore, generic drugs play a pivotal role in the sustainability of
the US health system. A generic drug is approved on the basis of sufficient demonstration of sameness to the
corresponding brand-name drug. Critical evidence for approval is bioequivalence (BE). Even though well
established, pharmacokinetic-based BE studies are both costly and lengthy. In the case of orally administered
drug products, co-administration with food may influence oral absorption, thus BE should be demonstrated under
both fasting and fed conditions if the reference listed drug labeling states the product can be taken with or without
meals. This requirement poses an additional financial burden on generic manufacturers, which will ultimately be
passed along to patients. Furthermore, the regulatory requirement of two in vivo BE studies slows down the
generic drug product development process and may increase review cycles and attrition rates due to variability
that is related to the drug itself rather than the formulation.
Quantitative methods and modeling have been widely used in the realm of new drug discovery and development
to inform more efficient and cost-effective development programs. Physiologically-based pharmacokinetic
(PBPK) modeling is one of the key tools under the overarching umbrella of quantitative models. PBPK models
are an effective tool to integrate information about the product characteristics, the physiology of the individual
subject, and the variability among subjects within a population to simulate the absorption and subsequent
systemic disposition of the drug without conducting in vivo PK studies. PBPK models have shown promise in
supporting generic drug development and regulatory decision-making, since, under a model-integrated evidence
perspective, it enables the leveraging of all prior knowledge generated to support the regulatory approval of the
respective brand-name drug product.
We will develop a best practices framework for integrating drug and drug product data together with
gastrointestinal physiology in PBPK models tailored to oral drug administration to predict food-formulation
interactions and promote biowaivers of fed state BE studies for poorly soluble and highly permeable drugs. This
will be done at both the individual and population levels. We have excellent in vitro testing and PBPK modeling
capabilities, along with unique PK and luminal drug concentration data sets. Once established, this framework
can also be applied to address emerging issues in generic drug development and assessment, such as BE study
protocol changes necessitated, for example, by pandemic situations and hypochlorhydria-formulation
interactions.

## Key facts

- **NIH application ID:** 10454243
- **Project number:** 5U01FD007352-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Rodrigo Cristofoletti
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2022
- **Award amount:** $299,965
- **Award type:** 5
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454243

## Citation

> US National Institutes of Health, RePORTER application 10454243, Development and validation of a best practices framework for PBPK analysis for biopharmaceutic applications in support of model-informed biowaivers of fed state BE studies for BCS class II drugs (5U01FD007352-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10454243. Licensed CC0.

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