A Professional Perspective on the FDA Roadmap Announcement on “Phasing Out” Animal Testing Requirements

The FDA’s Roadmap to Reducing Animal Testing in Preclinical Safety Studies announcement in April 2025 for “phasing out” animal testing requirements has been in process for several years. In fact, there have been announcements and publications on this “roadmap” since 2004—but the endeavor formally launched in 2008 with the Toxicology in the 21st Century (Tox21) Consortium, a collaboration among the U.S. Environmental Protection Agency (EPA), the National Institute of Environmental Health Sciences (NIEHS), the National Center for Advancing Translational Sciences (NCATS), and the FDA. 

Ethically speaking, reducing the use of animals for toxicology testing is the right thing to do. Scientifically and practically speaking, we’ve known for decades that we need more human-relevant models, and this reflects a growing commitment to more humane, responsible science. All of us within the industry must continue to push forward progress for this shared goal. This still must be balanced for the need to protect patient and public health.

Key Milestones and Cooperative Frameworks

This shift didn't happen overnight; it has its roots in the longstanding efforts to improve toxicity testing of chemicals. The modernization movement began with the Tox21 report, which called for more efficient and predictive methods to assess chemical toxicity. In 2007, the National Academies of Sciences expanded on this vision, emphasizing that developing, improving, and validating new laboratory tools—grounded in recent scientific advances—could significantly enhance our ability to understand the hazards and risks posed by chemicals.

This pivotal report built upon the National Toxicology Program (NTP’s) earlier framework and laid out a roadmap for implementing non-animal approaches. It advocated for a new paradigm centered on mechanism-based testing, using human biology and high-throughput screening technologies. The Tox21 Strategic Roadmap followed in 2011, outlining a formal federal collaboration to advance new approach methodologies (NAMs). The FDA joined this effort with its Predictive Toxicology Roadmap in 2017, which focused on applying NAMs in food and drug regulation. In 2021, the FDA issued an Alternatives Methods Progress Report, highlighting its work in the development and use of non-animal methods.

A 2023 Tox21 fact sheet provided the most recent update, summarizing progress in assay development, data integration, and interagency collaboration to further reduce reliance on animal models.

CDER Publications and Progress in NAMs

The FDA’s Center for Drug Evaluation and Research (CDER) has outlined its evolving approach to nonclinical testing through a series of published articles. A 2020 publication presents CDER’s perspective on integrating classical toxicology approaches with NAMs. In 2021, another article reviewed CDER’s application of the 3Rs—replacement, reduction, and refinement of animal testing, highlighting the past efforts and future directions.

Several efforts have also explored the use of microphysiological systems (MPS), also known as “organs-on-chips”, as potential alternatives to traditional animal models. Some of this work has focused on MPS developed using animal-derived cells or tissues, aiming to improve translational relevance while still relying on non-human biological sources. To date, these systems have largely been used to supplement rather than replace standard toxicology studies.

Legislative and Regulatory Shifts

A slight change in wording in the December 2022 legislation FDORA (Food and Drug Omnibus Reform Act of 2022, also referred to as the FDA Modernization Act 2.0) replaced “preclinical tests (including tests on animals)” with “nonclinical tests”, but didn’t remove a requirement for animal safety studies.

Around the same time, Science.org had published the assessment A new path to new drugs: Finding alternatives to animal testing, which explores how scientific and regulatory communities are embracing non-animal technologies like organ-on-chip, computational models, and human cell-based assays to improve drug development. NAMs that offer biological relevance can reduce reliance on animal studies, while still supporting faster, accurate safety assessments.

It was clear from many FDA meetings and presentations that getting to acceptable NAMs for regulatory decision-making was not going to be a straight path. Last year the FDA’s Associate Director for Pharmacology and Toxicology, Paul Brown, presented at a session at the DIA/FDA Oligonucleotide-Based Therapeutics Conference on this topic, posing the question “What does this all mean?”

His explanation revealed that the law requires drug developers to demonstrate that a product is reasonably safe for clinical testing, but doesn’t specify which types of studies—animal, in vitro, or others—must be used. The decision depends on whether the method is available, reliable, and scientifically valid.

In short, developers have flexibility in how they prove safety, as long as the method they choose is scientifically sound and validated. The FDA continues to accept animal testing as an established approach—reflecting its goal to ensure safety, not to prescribe how that goal is achieved.

The April 2025 Announcement From the FDA

In October 2024, the FDA Science Board presented its report on this topic, outlining several forward-looking proposals. Many of these, including calls for centralized approaches and consistent frameworks across the agency, were notably absent from the FDA’s April 10th announcement. 

Instead, the announcement focuses on a collaboration with the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)—a step that introduces practical and scientific challenges and could affect the FDA’s broader regulatory role. Other recommendations, such as allowing more flexibility in guidance, are already within the agency’s authority and do not represent significant change. The announcement also highlights the use of international human data, though this is already standard practice.

Another point raised from what was presented, is the “routine” use of six-month non-human primate studies. However, data supporting changes to this practice were made available over a decade ago, during the revision of ICH S6, and updates are long overdue. 

The proposed shift to a one-month animal study supported by NAMs assays, followed later with a three-month study, does little to meaningfully reduce animal use. In fact, most antibody developers already conduct a one-month study for FIH initiation and then conduct one chronic study (generally 6-month) except in oncology, where a three-month study will support Phase III trials or when submitting a biologics license application (BLA).

The National Association for Biomedical Research put out a statement in response to the FDA announcement. In it they note that despite all efforts to look at non-animal alternatives, there are still no full replacements for the use of animal models. The potential use of artificial intelligence (AI) to replace animals also depends on the database of information used to train the AI tools which would mean organizations having to share proprietary data which we know will be a major challenge, and so we are a very long way from being able to substitute an AI model for a whole animal model.

Looking Ahead

In summary, while the FDA’s April announcement represents another step in the right direction, its timing—and departure from earlier recommendations—raises important questions with no clear answers. The emphasis on ICCVAM collaboration presents challenges, and key proposals—such as the development of centralized frameworks—were notably absent, making this a much longer-term shift than initially believed. The departure of key FDA scientists involved in this work may further slow progress; however, the continued effort signals a sustained commitment to advancing scientifically sound, human-relevant alternatives.

About the Author

Mary Ellen Cosenza, PhD, BA, DABT, ATS, RAC (US/EU), ERT, is a regulatory

 toxicology consultant with over 35 years of leadership experience in the biopharmaceutical industry, including two decades at Amgen. She is well-published in the field of biological drug development and actively contributes to the toxicology community as President of the Academy of Toxicological Sciences, Treasurer of the International Union of Toxicology (IUTOX), and past president of the American College of Toxicology (ACT).

She is currently President of MEC Regulatory & Toxicology Consulting LLC and an adjunct professor at USC School of Pharmacy.

Connect with Mary Ellen on LinkedIn. 

_{This article was originally published in August 2025.}