Federal agencies are shifting away from animal testing toward human-based research models that promise faster, more accurate drug development. The National Institutes of Health (NIH) and Food and Drug Administration (FDA) are increasingly supporting new approach methodologies, or NAMs, which include organoids, organ-on-chip systems, and advanced computer modeling to evaluate drug safety and efficacy.

Why Are Researchers Moving Away From Animal Models?

Animal studies have long been the gold standard for testing whether drugs are safe before human trials begin. However, scientists have discovered a critical problem: what works in mice or dogs often fails when tested in people. Studies show that many treatments appearing promising in animals later flop in human clinical trials, largely because animal biology does not always predict human responses. Differences in genetics, metabolism, immune systems, and physiology create a translation gap that costs time and money.

Beyond scientific limitations, ethical concerns drive the shift. The scientific community has embraced the "3Rs" principle: replacement, reduction, and refinement. These guidelines encourage researchers to replace animals with alternative methods when possible, reduce the total number of animals used, and refine procedures to minimize pain or distress.

What Are These New Research Technologies?

NAMs represent a toolkit of human-based approaches designed to better mimic how drugs interact with the human body. These emerging technologies include:

• Organoids: Three-dimensional structures grown from human stem cells that mimic features of organs such as the liver, brain, or intestines, allowing researchers to study disease progression, infection, toxicity, and drug responses in human tissue.
• Organ-on-chip systems: Microfluidic devices that combine engineering and biology to recreate aspects of human organ function, simulating blood flow, breathing movements, and tissue interactions without using animals.
• Computer modeling and artificial intelligence: Systems that analyze large datasets, identify patterns, and predict biological responses, helping researchers evaluate toxicity risks, identify drug candidates, and model disease pathways.

These approaches aim to improve prediction of human responses while simultaneously reducing or eliminating animal use in research and testing.

How Are Federal Agencies Supporting This Shift?

The NIH has become a major champion of human-based research technologies. In recent years, NIH leaders have emphasized developing methods that better reflect human biology. The agency launched the Complement-ARIE program to accelerate development and use of alternative research approaches. In 2025, the NIH announced additional efforts to prioritize human-based technologies in research programs, recognizing that improving human relevance may help address high failure rates in clinical development.

The FDA is also taking concrete steps to reduce animal testing. Although many regulatory pathways still require animal data, the agency has published strategic roadmaps describing how it plans to incorporate NAMs into regulatory science. These efforts include evaluating new testing tools, developing standards for validation, and supporting collaboration between government agencies, industry, and academic researchers. The FDA and NIH jointly organized a collaborative workshop focused on reducing animal testing and promoting alternative methods.

The movement is not limited to the United States. The European Medicines Agency (EMA) has published guidance on regulatory acceptance of NAMs aimed at reducing animal use, while Japan's Pharmaceuticals and Medical Devices Agency (PMDA) is exploring innovative testing approaches, demonstrating that the transition toward alternative methods is becoming a global trend.

What Challenges Remain for These New Methods?

Despite growing enthusiasm, significant hurdles remain before NAMs can fully replace animal models. Regulators and researchers need strong evidence that alternative methods are reliable and reproducible. A method that works well in one laboratory must also work consistently in other settings. Validation can take years and may require extensive comparison with existing testing approaches. Regulatory agencies must determine whether new tools provide information equal to or better than traditional methods.

Human biology is extraordinarily complex. No single model can fully replicate the interactions among organs, immune systems, hormones, and environmental influences. Animal models also have limitations, but they can sometimes capture whole-body interactions that are difficult to recreate in laboratory systems. As a result, many experts believe research will continue using combinations of animal and non-animal approaches for the foreseeable future.

Additionally, modern research generates large and complex datasets. Integrating information from organoids, computational systems, imaging technologies, and genetic analyses can be difficult. Researchers must develop new standards for interpreting and sharing data generated by NAMs.

Steps to Support the Transition to Alternative Research Methods

• Professional training: Researchers and institutional professionals can pursue training in the 3Rs principles to enhance animal welfare, reduce total animal numbers while ensuring scientific validity, and replace animals with scientifically valid alternatives.
• Validation and standardization: Regulatory agencies and research institutions must establish clear standards for how NAMs data should be generated, interpreted, and shared across laboratories to ensure reproducibility.
• Collaborative infrastructure: Government agencies, industry, and academic researchers need to work together to develop frameworks for evaluating and accepting new technologies, as demonstrated by FDA and NIH joint workshops.

Advances in organoids, tissue chips, artificial intelligence, and computational science are creating new opportunities to improve the relevance and efficiency of research. Federal agencies such as the NIH and FDA are focused on using these technologies, while international regulators are developing frameworks for their evaluation and acceptance. Validation, standardization, and infrastructure will all play critical roles in determining how quickly NAMs continue to advance.