Are We Ready for a Future Without Animal Testing?

Reducing the use of animals in research has long been a scientific and ethical ambition. Last year, that ambition took a major step toward becoming a regulatory priority.

In April 2025, the US Food and Drug Administration (FDA) announced plans to gradually replace animal-testing requirements for new drug approvals within the next three to five years. Building on the momentum of the FDA Modernization Act 2.0. The agency aims to increase the use of New Approach Methodologies (NAMs), including organ-on-a-chip systems, organoids, computational modelling, and artificial intelligence.

Shortly after, the National Institutes of Health (NIH) announced a similar direction. They state that future funding opportunities should support human-focused in vitro approaches and move away from studies relying solely on animal models.

These announcements represent a major shift in biomedical research. But they also raise an important question: are human-relevant technologies ready to replace animal testing?

A recent perspective article by Donald Ingber explores this question in depth. Drawing on more than 15 years of experience developing and commercializing Organ Chip technology, Ingber discusses both the opportunities and challenges for organ-on-a-chip technologies. Facing the field as regulators, industry, and researchers work toward broader adoption of NAMs.

From Promising Science to Trusted Technology

One of Ingber’s key messages is that scientific innovation alone is not enough. For regulators and industry to embrace NAMs, technologies must be robust, reproducible, and standardized.

Many organ-on-a-chip systems originated in academic laboratories, where devices are often custom-built and experimental conditions vary between groups. While these platforms have demonstrated impressive scientific value, regulatory acceptance requires something different: confidence that the same experiment can generate consistent results regardless of who performs it or where it is performed.

This challenge is familiar across the NAM landscape, including gastro-intestinal research. Researchers need models that capture human biology while remaining practical and reproducible enough to support decision-making. This philosophy has long been central to the TIM® platform. For decades, TIM® systems have provided standardized and reproducible simulations of the human gastro-intestinal tract. It helps enabling researchers to evaluate food, supplements, and pharmaceuticals under controlled conditions. TIM Cell builds on this by integrating human intestinal cells into a dynamic gastro-intestinal environment, combining physiological relevance with experimental consistency.

Capturing Human Physiology

One reason NAMs have attracted so much attention is the growing recognition that animal models do not always predict human outcomes accurately.

Human biology is complex. Drug absorption, metabolism, efficacy, and toxicity are influenced by factors that can be difficult to reproduce in animals. Organ-on-a-chip technologies attempt to bridge this gap by recreating key aspects of human physiology using human cells, tissue interfaces, and dynamic culture conditions.

According to Ingber, one of the greatest strengths of these systems is their ability to capture meaningful human variability. While variability is often viewed as a challenge, it is also a reflection of reality. Patients differ from one another, and understanding those differences is essential for improving clinical translation.

How TIM® Captures Human Variability

TIM Cell is an organ-on-a-chip technology that combines dynamically generated human intestinal fluid with intestinal cells in a millifluidic chip environment to model permeability. But it is designed to capture human variability from a different angle than Ingber describes. Rather than varying the donor behind the cells, TIM Cell is a key component of the broader TIM® platform that varies the physiology those cells are exposed to.

That physiology comes from TIM® in vitro gastro-intestinal systems. One of the key benefits of these TIM® systems is that physiological parameters can be varied. Not to represent just the average subject, but the upper and lower extremes present within a population. In fact, all parameters in the TIM® systems are computer-controlled, namely gastric and intestinal emptying, pH profiles, bile and enzymatic levels and motility. This means that not only average, upper and lower ends of the population can be simulated in vitro. Also any subject within the whole spectrum of a population by adjusting one or more TIM® parameters.

Another cause of human variability that can be characterised using TIM® are the intake conditions. As TIM® incorporates digestion, even the effects of different types and quantities of food and drinks on drug product performance in the gastro-intestinal tract can be investigated. For example, standardised meals from the FDA and European Medicines Agency (EMA) containing eggs and bacon, pediatric soft food, or beverages like coca-cola.

After evaluating, a drug product’s critical bioavailability attributes. Its performance can be tested in the in vitro GI tract under TIM® physiologies that represent the extremes of inter-subject variability. Offering a view of how population variability affects dissolution and bioaccessibility.

From Physiological Variability to Clinical Relevance

TIM Cell is built to bring that same predictive power to permeability. By sampling from experiments in TIM Upper GI models run under different physiologies, such as different bile levels, or administration of different real food meals. TIM Cell shows how permeability itself may vary across a population or day-to-day within a subject.

Finally, TIM PK feeds this data into physiologically based pharmacokinetic (PBPK) models. It tests whether the differences seen in gastro-intestinal dissolution and permeability in vitro are predicted to translate into clinically meaningful pharmacokinetic differences,. This offers a patient-centric approach to drug product development, with not just the average subject in mind. Where Ingber’s Liver Chip captures variability by drawing on cells from different real donors, TIM Cell captures it by systematically varying the physiological environment those cells sit in. Both organ-on-a-chip technologies taking on the same challenge, representing human variability, not just the human average, but from different directions.

Moving beyond static models, on to dynamic models

A recurring theme throughout Ingber’s article is the importance of dynamic physiology.

In the human body, tissues are constantly exposed to changing conditions. Nutrients, drugs, enzymes, metabolites, and microbiota interact in a highly dynamic environment. Yet, many laboratory models remain static. They’re exposing cells to a single concentration of a compound for a fixed period of time.

Organ-on-a-chip technologies seek to address this limitation through fluid flow, mechanical stimulation, and realistic exposure profiles. These features help recreate the conditions cells experience in vivo and can improve the relevance of experimental findings.

The same principle underlies the TIM® platform. Digestion is not a static process, pH changes over time, enzymes are released gradually, compounds dissolve and precipitate, and nutrients move through different regions of the gastro-intestinal tract. By incorporating these dynamic processes, TIM® systems have helped researchers generate more physiologically relevant insights for many years.

Combining these dynamic digestive conditions with cellular readouts in TIM Cell creates exciting opportunities to investigate how formulations, ingredients, and pharmaceuticals interact with the intestinal environment in a more realistic manner.

Looking to the future, what is next?

While much of discussions surrounding NAMs focuses on reducing animal testing, Ingber argues that the greatest opportunity may lie elsewhere.

Human-relevant models have the potential to improve our understanding of drug efficacy, mechanisms of action, patient variability, and disease biology. Long before a compound reaches clinical trials. When combined with advances in artificial intelligence and computational modelling, these technologies may help researchers make better decisions earlier in development, reducing costs and improving success rates.

For gastro-intestinal research this could mean more accurate prediction of absorption, improved understanding of formulation performance, and deeper insight into how compounds interact with the intestinal barrier and surrounding environment.

Despite the excitement surrounding NAMs, Ingber is realistic about the road ahead. Animal testing is unlikely to disappear overnight, and widespread adoption of human-relevant technologies will require continued validation, standardization, and regulatory acceptance.

However, the recent actions by the FDA and NIH represent a significant shift in direction. The question is no longer whether human-relevant models will play a role in future research, but how quickly it can be integrated into existing workflows.