How New Approach Methodologies Are Replacing Animal Testing in Drug Development
- Non-animal testing methods, known as NAMs, are reshaping drug development as global regulators move away from mandatory animal trials, though researchers face steep validation hurdles and entrenched lab...
- Back when cell biologist Donald Ingber and his colleagues at Harvard University’s Wyss Institute for Biologically Inspired Engineering sent a manuscript to the journal Science 17 years ago,...
- Regulatory frameworks have evolved to accommodate these technologies.
Non-animal testing methods, known as NAMs, are reshaping drug development as global regulators move away from mandatory animal trials, though researchers face steep validation hurdles and entrenched lab habits. Driven by the 2022 passage of the FDA Modernization Act 2.0 and subsequent regulatory shifts by agencies in the United States, Europe, and the United Kingdom, the biomedical field is slowly transitioning toward human-cell systems, organs-on-chips, and computer simulations to predict drug safety and efficacy.
Evolution of Organ-on-a-Chip Technology
Back when cell biologist Donald Ingber and his colleagues at Harvard University’s Wyss Institute for Biologically Inspired Engineering sent a manuscript to the journal Science 17 years ago, it detailed a human lung model no larger than a USB stick. Built from a clear polymer slab with narrow channels lined by human lung and blood vessel cells, the device rhythmically expanded and contracted when air was pumped through adjacent hollow chambers. Initially, editors at Science rejected the study, requesting that the team run comparative tests in mice to validate the new technology. The paper was eventually published in 2010 after those mouse experiments were completed.
Today, the environment for these systems—collectively referred to as organs-on-a-chip or new approach methodologies (NAMs)—has shifted dramatically. Ilka Maschmeyer, a translational toxicology researcher and executive at the German biotech company TissUse, notes that pharmaceutical companies are approaching her firm after facing resistance from the U.S. Food and Drug Administration over animal-only data. According to Maschmeyer, the FDA requested data from organs-on-a-chip or comparable alternatives before permitting clinical trials for a new drug.
Beyond single organs like brains, hearts, kidneys, and placentas, developers have linked as many as 10 organ systems together to simulate complex human physiology. These technologies are supported by computational simulations and artificial intelligence tools that analyze generated data in iterative testing loops. For example, an Emulate liver-on-a-chip correctly flagged approximately seven out of every eight drugs that safely passed animal trials but proved toxic to human livers. Meanwhile, a heart-cell simulation developed by researchers from Oxford University and Janssen Pharmaceutica flagged compounds causing dangerous heart arrhythmias with 89 percent accuracy, outperforming animal studies rated at 75 percent accuracy.
Regulatory Overhauls and Policy Shifts
Regulatory frameworks have evolved to accommodate these technologies. The U.S. FDA Modernization Act 2.0 passed into law in late 2022, explicitly authorizing the use of NAMs in preclinical studies required before new drugs enter human trials. A commitment was made by the FDA in 2025 to make animal trials the exception rather than the standard for drug safety evaluations, which was followed up in September 2026 by an enacted rule substituting references to animal testing with the more encompassing phrase nonclinical tests. This regulatory update allows validated human-cell systems, organs-on-chips, and computer models to be utilized when appropriate.
Additional institutional pressures followed in 2025, when the U.S. National Institutes of Health announced that researchers applying for grants to study animal models must incorporate nonanimal research, such as real-world data or NAM studies. Similar phase-out plans have been announced by the European Commission and the United Kingdom, while the Organisation for Economic Co-operation and Development updated its guidelines to permit expanded use of NAMs. These shifts provide a crucial incentive for researchers, who previously faced few rewards for abandoning established animal models.
Validation and Standardization Challenges
Despite regulatory backing, implementing NAMs involves complex validation and standardization challenges. Pointing to change management rather than technology as the primary hurdle, Thomas Hartung serves as a toxicologist and directs the Center for Alternatives to Animal Testing at Johns Hopkins University. Standardizing workflows, experimental guidelines, metrics, and reporting criteria remains difficult. Even minute variations in hydrogels used as tissue scaffolds in organ chips can produce significantly different growth patterns, requiring commercial products to meet rigorous mass-production performance criteria. Comprehensive validation studies are also costly and resource-intensive. Emulate’s liver-chip study required 870 chips and the labor equivalent of 16 full-time employees working for 16 weeks.
Inertia in Research Culture and Scientific Training
Adoption of NAMs is further slowed by cultural inertia within research institutions.