Replacement of Animal Testing in the United States 

Federal and State Strategies Driving a New Era of Safety Science  

Across the United States, a decisive shift is underway in how chemicals, pharmaceuticals, and consumer products are evaluated for safety. Long-standing reliance on vertebrate animal testing is being reconsidered in favour of scientifically advanced, human-relevant alternatives. At both the federal and state levels, lawmakers and regulators are modernizing statutes, guidance, and funding priorities to support the replacement, reduction, and refinement (3Rs) of animal testing. Efforts are increasingly focused on reducing reliance on animal models across different animal species, with multi-stakeholder collaboration, scientific validation, and regulatory acceptance playing a crucial role in advancing these alternatives. 

This blog explores the evolving U.S. regulatory and policy landscape, highlighting how federal reforms and state-level initiatives are accelerating the adoption of non-animal testing methods, including validated in vitro approaches such as Corrositex® (OECD TG 435) and reconstructed human tissue models for eye irritation (OECD TG 496)—services proudly offered by Dell Tech. The National Research Council’s 2007 report urged a shift toward human-relevant testing methods, which has influenced the development of programs like Tox21. 

From Animal Models to Human-Relevant Science  

For decades, traditional models involving animal experiments have been the default approach for evaluating toxicity, irritation, corrosion, and systemic effects. These methods were embedded in U.S. law following public health crises of the mid-20th century and were long viewed as the most conservative path to safety. 

However, mounting scientific evidence has shown that animal models frequently fail to predict human outcomes, particularly for toxicological endpoints such as skin corrosion, eye irritation, and systemic toxicity. At the same time, in vitro, computational, and micro-physiological systems have matured into reliable, reproducible, and internationally accepted alternatives. 

While replacing animal experiments is a key goal, phasing out animal testing too quickly raises concerns about safety and effectiveness. Rigorous validation of alternative methods is essential before they can fully replace animal testing. 

These developments, combined with ethical concerns, cost pressures, and the need for faster innovation, have catalyzed a policy shift across the United States toward animal-free safety science. 

Federal Leadership: Modernizing U.S. Testing Requirements  

FDA Modernization Act 2.0  

A landmark moment came in December 2022, when the FDA Modernization Act 2.0 was signed into law. This legislation amended the Federal Food, Drug, and Cosmetic Act to remove the long-standing requirement that new drugs be tested in animals before entering human clinical trials. The Act removed the statutory animal-test mandate, allowing for the use of non-animal testing methods in drug development. 

Critically, the Act replaced references to “animal testing” with the broader term “nonclinical tests”, explicitly recognizing: 

• Cell-based assays 

• Organ-on-a-chip technologies 

• Computational and in silico models 

• Microphysiological systems 

• Other human-relevant methods 

Nonclinical tests, as defined by the Act, include in vitro, in silico, and microphysiological systems. The FDA’s plan and roadmap for minimizing animal testing include the adoption of New Approach Methodologies (NAMs) for monoclonal antibody testing and expanding their use to other drug types, as part of a phased approach to reduce and eventually phase out animal use in preclinical studies. 

While the law does not ban animal testing outright, it eliminates the federal mandate, giving regulators and sponsors the flexibility to rely on scientifically valid non-animal approaches when appropriate. This marks a significant shift in preclinical tests from traditional animal-based methods to innovative, non-animal-based approaches. 

FDA Roadmaps and Agency Direction  

Building on this statutory change, the FDA has publicly stated its long-term objective to make animal studies the exception rather than the norm for pre-clinical safety and toxicity testing. The FDA’s plan and roadmap outline a strategic approach for phasing out animal testing, and the FDA aims to make animal studies the exception rather than the norm for preclinical safety testing within three to five years. The FDA announces plan in 2025 to reduce, refine, or replace animal testing, beginning with monoclonal antibodies. Recent agency roadmaps emphasize: 

• Qualification and acceptance of New Approach Methodologies (NAMs) 

• Integration of AI-enabled toxicity prediction 

• Increased reliance on validated OECD test guidelines 

The FDA’s roadmap for phasing out animal testing includes a strategic approach for reducing animal testing in preclinical safety studies using scientifically validated NAMs. When discussing NAMs and AI-enabled toxicity prediction, it is crucial to ensure that these advancements do not result in compromising safety. The ethical implications of replacing animal testing with NAMs must be carefully considered to avoid compromising safety. 

This direction aligns closely with the corrosion and irritation endpoints, for which OECD-accepted non-animal methods already exist and are globally harmonized. 

NIH and Federal Research Funding Signals  

The National Institutes of Health (NIH), the largest funder of biomedical research in the U.S., has also begun shifting expectations. Recent policy statements and funding announcements make clear that: 

• Proposals relying exclusively on animal models are increasingly discouraged. In 2025, the NIH announced it would no longer focus funding on animal testing, favoring human-based technologies to reduce animal use in research. 

• The NIH is actively working to develop and validate human-based NAMs to reduce the use of animals in research. 

• Researchers are expected to justify animal use and consider alternatives 

• Human-relevant methods are prioritized for translational value 

This shift sends a powerful signal to industry and academia alike: animal testing is no longer the default benchmark of scientific rigor. 

EPA and Toxicity Testing Reform  

The U.S. Environmental Protection Agency (EPA) has played a particularly influential role in advancing non-animal testing for chemical safety. Under authorities such as the Toxic Substances Control Act (TSCA), the EPA has committed to eliminating mammalian testing for chemical safety by 2035 and prioritizing non-animal alternatives. The agency has: 

• Actively promoted NAMs for hazard identification 

• Published strategic plans to reduce vertebrate testing 

• Encouraged submitters to use OECD-validated in vitro methods where available 

• Supported the use of high-throughput screening to prioritize chemicals for further safety assessment, including tools like the Tox21BodyMap, which uses high-throughput screening data to predict organ-specific toxicity based on chemical structures 

For endpoints such as skin corrosion and eye irritation, EPA guidance increasingly aligns with international standards, creating regulatory confidence for companies that adopt non-animal methods early. This shift also reflects a move from reliance on animal data to the integration of non-animal data in regulatory submissions. 

State-Level Action: Innovation from the Ground Up  

While federal reforms set the tone, U.S. states have emerged as powerful drivers of the replacement of animal testing, particularly in consumer product sectors. Many states have also introduced initiatives that align with the 3Rs principle, specifically aiming to refine animal testing practices. These efforts focus on the ‘refine animal’ aspect by improving experimental methods to minimize pain and distress for animals used in research. 

Cosmetics Testing Bans  

Several states, including California, New York, New Jersey, Illinois, Virginia, and Nevada, have enacted laws prohibiting the sale of cosmetics tested on animals. These statutes:  

• Explicitly recognize the availability of non-animal alternatives  

• Reinforce alignment with global cruelty-free markets  

• Create de facto incentives for NAM adoption across supply chains  

Research and Procurement Policies  

Some states have also begun incorporating non-animal testing preferences into: 

• Public research funding programs 

• State procurement and sustainability policies 

• University research ethics frameworks, with the scientific community playing a key role in promoting the adoption of non-animal testing methods and advancing ethical research practices. 

Collectively, these measures reinforce a national trend: companies that rely on animal testing face increasing regulatory and commercial friction. 

Why Corrosion and Irritation Testing Are Leading the Transition  

Among toxicological endpoints, skin corrosion and eye irritation stand out as areas where animal testing replacement is already fully achievable. New alternative methods (NAMs), such as organs-on-chips and the use of human cells, are increasingly being adopted to improve predictive accuracy and reduce reliance on animal testing. 

OECD-Validated Non-Animal Methods 

Internationally accepted OECD test guidelines now allow companies to assess these hazards without live animals, including: 

• OECD TG 435 – Corrositex®  A membrane barrier system that classifies skin corrosion potential based on physicochemical reactivity. 

• OECD TG 496 – Reconstructed Human Cornea-like Epithelium (RhCE)  An in vitro method for eye irritation and corrosion classification using human-derived tissue models. 

Organ-on-a-chip devices lined with human cells can simulate blood flow and organ-level functions, aiding in the prediction of drug-induced liver injury. Key advancements in NAMs include organ-on-a-chip technology, 3D organoids, AI-driven computer modeling, and in vitro cell cultures. Organ-on-a-chip technology allows researchers to study physiological responses, disease, and drug metabolism in real-time without using animals. 3D organoids replicate complex human tissues and are used in studies like Zika virus and cancer research. Microphysiological systems and human-derived organoids are improving cancer research through personalized screening methods. 

These methods are recognized by U.S. regulators, accepted for GHS classification, and increasingly expected as first-tier approaches. 

Dell Tech’s Role in Supporting U.S. Regulatory Evolution 

As regulatory expectations evolve, Dell Tech supports companies navigating this transition with validated, cruelty-free testing solutions that meet both U.S. and international requirements. 

Benefits of Alternative Test Methods 

The adoption of alternative testing methods is revolutionizing the landscape of safety science, offering a host of advantages over traditional animal testing. By embracing innovative approaches such as organ-on-a-chip technology, microphysiological systems, and AI-based computational modeling, researchers are able to mimic human organs and biological processes with unprecedented accuracy. These human-relevant methods provide data that is more predictive of real-world outcomes, reducing the reliance on animal models that often fail to fully represent human biology. 

One of the most significant benefits of these alternative methods is the reduction in the use of laboratory animals for toxicity testing and drug evaluation. This shift not only addresses longstanding ethical concerns about animal welfare and humane experimental technique, but also aligns with the principles of the 3Rs—Replacement, Reduction, and Refinement—by minimizing animal suffering and promoting laboratory animal welfare. Animal welfare organizations and responsible medicine advocates, such as the Physicians Committee for Responsible Medicine and the National Institutes of Health, have championed these changes, recognizing the importance of reducing animal use in biomedical research. 

Alternative testing methods also offer practical advantages for drug development and chemical safety. By leveraging advanced computer models, machine learning, and human-based technologies, researchers can accelerate the preclinical testing phase, identify potential risks earlier, and generate strong safety data without compromising human safety. This not only speeds up the introduction of new drugs and monoclonal antibody therapies to clinical trials, but also reduces the costs and time associated with animal experimentation. 

The regulatory landscape is evolving to support these advancements. The FDA Modernization Act 2.0 and subsequent updates have removed the federal animal testing requirement for new drugs, paving the way for regulatory acceptance of non-animal methods. Federal agencies, including the FDA and the Interagency Coordinating Committee, are actively encouraging the use of new approach methodologies (NAMs) and innovative methods that prioritize human biology and public health. 

Beyond the scientific and regulatory benefits, the move toward alternatives to animal testing is helping to build public trust in the safety of new drugs and chemicals. By using non-animal tests that better mimic the human body, companies can demonstrate a commitment to both scientific rigor and ethical responsibility. 

Our Non-Animal Hazard Classification Services  

Dell Tech offers: 

• Corrosivity to Skin Testing (OECD TG 435 – Corrositex®) 

• Eye Irritation and Corrosion Testing (OECD TG 496) 

These non-animal methods are increasingly used for drug testing, providing innovative alternatives to traditional animal-based approaches. Computational models and organ-on-a-chip technologies are examples of New Approach Methodologies (NAMs) that can offer safer and more effective drug testing alternatives. 

These services enable manufacturers to: 

• Eliminate vertebrate animal use for key hazard endpoints 

• Align with FDA, EPA, and state-level policy direction 

• Support global submissions under GHS, TSCA, and international frameworks 

📎 Learn more: 

• Corrosivity to Skin Testing – Corrositex® (OECD TG 435))) 

• Eye Irritation and Corrosion Testing (OECD TG 496)))  https://delltech.com/services/lab-services/hazard-classification/ 

Strategic Alignment  

By adopting these methods, companies are not merely meeting current requirements—they are future-proofing their compliance strategies in a regulatory environment that increasingly favors NAMs. Additionally, adopting NAMs can enhance drug safety by providing more accurate, human-relevant assessments, which helps ensure safer and more effective drugs while reducing reliance on animal testing. 

Looking Ahead: The U.S. Path to Animal-Free Safety Science  

The United States is not moving toward a single sweeping ban on animal testing. Instead, it is executing a deliberate, science-driven transition: Ongoing efforts must address the challenges of replacing animal experiments and animal research across different animal species, ensuring that new methods are both effective and safe. Comparing animal data with NAM evidence is essential to validate new testing approaches and build regulatory confidence. The FDA and NIH are collaborating to establish pathways for validating New Approach Methodologies (NAMs) as alternatives to animal testing. A careful, step-by-step approach is crucial for reducing animal testing in preclinical studies, and the introduction of a premarket review or certification process for NAMs could help ensure their reliability before they replace animal testing. 

• Federal law now permits non-animal methods where scientifically justified 

• Agencies are actively encouraging NAM development and use 

• States are raising the bar through targeted legislation 

• Industry is responding with innovation and early adoption 

For endpoints such as skin corrosion and eye irritation, the question is no longer whether animal testing can be replaced, but why it would still be used at all. 

Opportunity Through Innovation  

The replacement of vertebrate animal testing in the United States represents both a regulatory evolution and a competitive opportunity. The FDA has announced its commitment to replacing animal testing in developing monoclonal antibodies and other drugs with New Approach Methodologies (NAMs). This includes a pilot program allowing select monoclonal antibody developers to use a primarily non-animal-based testing strategy. Artificial intelligence and AI-based computational models, such as the FDA’s AnimalGAN, are now used to predict human reactions and replace animal tests for toxicity prediction. Additionally, artificial intelligence and machine learning are utilized to predict drug toxicity and safety by analyzing molecular structures. Companies that embrace validated non-animal methods today position themselves as: 

• Scientifically progressive 

• Ethically responsible 

• Aligned with future regulatory expectations 

Dell Tech is proud to support this transition by providing trusted, cruelty-free testing solutions that meet the highest scientific and regulatory standards—helping clients move confidently toward a safer, more humane future.