International Inter-laboratory Study Demonstrates Reproducibility of TIM®

Most extensive validation study to date support the value of TIM^® systems

A newly published scientific study demonstrates that the TIM^® gastrointestinal (GI) modeling platform delivers highly reproducible results across multiple international laboratories, confirming the robustness of the systems for studying oral drug product performance.

The study, published last week in the journal Pharmaceutics, evaluated the performance of the TIM-1 and tiny-TIM dynamic in vitro models in a coordinated inter-laboratory study involving seven research laboratories across six countries. Despite the complexity of these systems and the dynamic physiological processes they simulate, the results showed strong reproducibility between participating laboratories, with variability within established regulatory benchmarks for dissolution data quality.

As the most extensive inter-laboratory validation study of the TIM^® systems to date, the findings support the value of TIM^® systems as biorelevant tools for pharmaceutical research and development and provide a foundation for future regulatory interactions involving TIM^® data.

In the study, participating laboratories performed standardized experiments using harmonized protocols to evaluate the performance of oral drug formulations under simulated gastrointestinal conditions. The results showed consistent and comparable outcomes between laboratories, confirming that the TIM^® systems can generate reliable data even when operated in different facilities and research environments.

To successfully predict what is happening in the human body in vivo, in vitro models must provide reliable and well-understood predictions of the release, dissolution, and absorption of the active pharmaceutical ingredient (API). Achieving this requires close replication of the complex and dynamic environment of the gastrointestinal (GI) tract. Biorelevant in vitro methods are increasingly used to study the mechanisms controlling oral bioavailability and align with the growing adoption of New Approach Methodologies (NAMs) and regulatory initiatives such as the FDA Modernization Act 2.0.

While compendial United States Pharmacopeia (USP) dissolution methods remain valuable for high-throughput quality control testing, their relatively simple conditions limit their physiological relevance and biopredictive power. In contrast, dynamic gastrointestinal systems such as TIM-1 and tiny-TIM accurately mimics key processes of GI transit, capturing luminal conditions in the stomach and small intestine.

Although the physiological relevance and biopredictive performance of the TIM^® systems have been demonstrated extensively, systematic evaluation of their repeatability and reproducibility across laboratories has been limited. Current demonstration of the observed high reproducibility across laboratories is essential to further strengthen scientific and regulatory confidence.

Full reference

O’Farrell, C., Havenaar, R., McAllister, M., Hens, B., Barker, R., Mármol, Á. L., Ansari, A., Ooms, T., Schilderink, R., Schwabe, R., Butler, J., Stróžyk, M., Martins Garcia, T., Minekus, D., Sarcevica, I., Smith, K., Tomaszewska, I., Jones, E., Batchelor, H., & Bellmann, S. (2026). TIM-1 and Tiny-TIM as Robust In Vitro Models for Oral Biopharmaceutics: Evidence from an International Ring Study. Pharmaceutics, 18(4), 400. https://doi.org/10.3390/pharmaceutics18040400

Link to the full article here