# From Bench to Bioequivalence: In Vitro Mechanistic Understanding of ASD Drug Products in Simulated Gastrointestinal Conditions

> **NIH FDA U01** · SIMULATIONS PLUS, INC. · 2024 · $249,485

## Abstract

From Bench to Bioequivalence: In Vitro Mechanistic Understanding of ASD Drug
Products in Simulated Gastrointestinal Conditions
– Project Abstract
 The findings from this project will enhance our comprehension of how food and gastric pH
affects the release of drugs from ASDs, and how the variability arising from differences in
formulations and manufacturing can impact upon in vivo performance. This project will generate
Tiny-TIMsg data on a series of amorphous solid dispersion (ASD) drug products under fasted;
fed and reduced gastric pH conditions and correlate this in vitro data to in vivo clinical data. In
the second step, a mechanistic modeling-based methodology will be employed to link the in vitro
dissolution obtained in the Tiny-TIMsg system to the in vivo performance of ASD drug products.
Using this in silico model, clinical performances of ASD formulation variants will be simulated,
and virtual BE (VBE) conducted to assess the impact of formulation and manufacturing process
modification on API’s exposure.
 The series of ASD drug products will be carefully selected to ensure that there is diversity in
products based on: method of manufacture; excipient composition and the ratio of stabilizing
polymer:API. Access to clinical data is critical in the selection of products hence the initial focus
will be on the identification of relevant data sets. All products to be tested will be interrogated to
identify data on degree of solubility enhancement required; pH dependent solubility and reported
food effect. Where formulations are not commercially available they will be manufactured to
match reported parameters using dissolution matching as the primary target.
 Output data from the Tiny-TIMsg will report the ratio of bioaccessible dose in either the fed
or the reduced gastric pH state to the fasted state; this will be correlated to the clinical data of
the ratio of the AUC in the fed or the reduced gastric pH state to the fasted state. Each
formulation’s performance in the Tiny-TIMsg will be closely interrogated to identify the kinetics
of precipitation to mechanistically understand ASD performance. The closely controlled and
reproducible nature of Tiny-TIMsg will enable discrimination at a level not possible with pre-
clinical or clinical testing; hence the ability to discriminate between formulations and identify risks
associated with food or reduced gastric pH in the prediction of in vivo outcomes. Coupling the
Tiny-TIMsg data to PBPK models will support formulation development and minimize future
clinical testing thus accelerating the speed of development of safe and effective medicines. The
developed and validated workflow will help to establish scientific and regulatory standards for
supporting innovative development of ASDs and performing virtual bioequivalence evaluation of
these generic drug products.

## Key facts

- **NIH application ID:** 11064251
- **Project number:** 1U01FD008388-01
- **Recipient organization:** SIMULATIONS PLUS, INC.
- **Principal Investigator:** Maxime Le Merdy
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2024
- **Award amount:** $249,485
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11064251

## Citation

> US National Institutes of Health, RePORTER application 11064251, From Bench to Bioequivalence: In Vitro Mechanistic Understanding of ASD Drug Products in Simulated Gastrointestinal Conditions (1U01FD008388-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/11064251. Licensed CC0.

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