On April 10, 2025, the U.S. Food and Drug Administration (FDA) announced a new initiative to explore ways to reduce preclinical animal safety studies for human drugs and biological products, beginning with an approach to allowing the use of “New Approach Methodologies” (NAMs) in lieu of animal testing for eligible investigational monoclonal antibodies.[1] The agency’s plan marks a significant departure from decades of agency practice, in which life sciences companies developing novel therapeutic products typically have conducted a number of safety studies, including pharmacological and toxicological studies, in various species before progressing to the clinical phase. Below are six key points for life sciences companies to know about FDA’s plans to incorporate NAMs into preclinical evaluations for human drugs and biologics.
- Roots in the FDA Modernization Act 2.0: The groundwork for the FDA roadmap was laid out in legislation, the FDA Modernization Act 2.0 (“FDAMA 2.0”) to reduce reliance on animal testing that was enacted in 2022.[2] FDAMA 2.0 replaced references to “preclinical” and “animal tests” in statutory language on testing required to initiate clinical testing, with the broader term “nonclinical tests.”[3] At the time FDAMA 2.0 was passed, FDA had taken the position that the law did not change the regulatory process for approving for drugs and biological products, and that it already had sufficient flexibility to consider alternative nonclinical tests prior to the statutory change.[4] Since its enactment, the lead sponsors of FDAMA 2.0, Senators Cory Booker and Rand Paul, have argued that FDA has not taken sufficient action to implement flexibilities for non-animal testing.[5]
- Ethics, costs, and clinical predictiveness: In the new roadmap, FDA states that its proposals are more cost effective, more ethical, and better-attuned to assessing likely clinical outcomes than animal studies. The agency asserts that animal studies have been poor predictors of therapeutic success in certain common diseases, including cancer, Alzheimer’s disease, and inflammatory diseases, due to physiological differences between humans and other animals. The agency also alluded to significant costs associated with animal studies and ethical concerns with the treatment of laboratory animals.
- Leveraging new technologies: FDA touts NAMs as potential alternative sources of safety data that it may accept in its review processes for INDs. NAMs can include: ex vivo human tissues from in vitro models and from organ donation and tissue preservation; in silico tools and computational modeling, including artificial intelligence and machine learning; and, high-throughput cell-based screening. FDA even suggests that NAMs can include certain studies that involve testing in humans, such as microdosing and imaging in human volunteers. FDA plans to encourage eligible sponsors to submit NAM data in parallel with conventional animal study data over the next three years as it evaluates its proposed approach, and to establish an open-access repository of international drug toxicity data from animals and humans.
- Monoclonal antibodies as a test case: FDA intends to use monoclonal antibodies as an initial test case for the new approach to NAMs because of the extensive FDA requirements for toxicity, pharmacokinetics, and safety pharmacology studies for these products. FDA also notes that some safety risks, such as cytokine release syndrome, have gone undetected in animal studies, supporting the need for a new approach. Together, these factors cause animal studies for monoclonal antibodies to be particularly expensive and time-consuming. FDA plans to reduce the routine 6-month primate toxicology studies required for these products to three months if they show no concerning signals in 1-month studies and NAM tests. FDA plans to explore whether reduced animal study requirements may be appropriate for other types of therapeutic agents. If implemented, these proposals could significantly expedite and reduce the costs for IND-enabling studies for monoclonal antibodies.
- A work in progress: FDA acknowledges in the roadmap that adopting NAMs in its decisionmaking requires further development. In particular, the agency intends to identify key safety and efficacy questions where NAMs can replace or augment animal data; support targeted development of NAM technologies; establish validation and qualification pathways for NAMs; and develop guidance for industry and internal training programs. FDA plans to work with the Interagency Coordinating Committee on the Validation of Alternative Methods, which includes 18 U.S. agencies, to help advance these goals.
- Challenges in implementation: FDA may face some obstacles in implementing the roadmap. First, as we have previously reported, FDA has suffered significant reductions in personnel who would be crucial to its plans under the roadmap, and its funding is also in question.[6] These issues likely will present obstacles to the agency’s ambitious goals, and it remains to be seen whether and, if so, when and it what form the roadmap will impact review of INDs and applications for marketing authorization. Second, as Senators Booker and Paul and others have noted, certain FDA regulations still expressly require animal tests for INDs and in marketing applications, and the agency has not yet engaged in the notice-and-comment rulemaking process—which can take years to complete—that is required to amend its regulations. Acknowledging this issue, Senator Booker has introduced a bill with a group of bipartisan cosponsors, including Senator Paul, the FDA Modernization Act 3.0 (“FDAMA 3.0”), which would require the agency to issue an interim final rule specifically updating various regulatory references to “animal” testing and data.[7]
Life sciences companies should continue to monitor these developments. Companies developing monoclonal antibodies, in particular, should consider engaging with FDA to see how they can use NAMs in their development programs and to provide input on FDA’s policy on NAMs moving forward.
[1] FDA, Roadmap to Reducing Animal Testing in Preclinical Safety Studies, available at https://www.fda.gov/media/186092/download?attachment; see also FDA News Release, “FDA Announces Plan to Phase Out Animal Testing Requirement for Monoclonal Antibodies and Other Drugs” (Apr. 10, 2025).
[2] Pub. L. No. 117-328, 136 Stat. 5807, § 3209(a)(1) (Dec. 29, 2022) (amending 21 U.S.C. § 355(i)(1)(A) and (i)(2)(B)).
[3] “Nonclinical tests,” in turn, were defined to include tests “conducted in vitro, in silico, or in chemico, or a nonhuman in vivo test . . . include[ing] the following: (1) Cell-based assays[;] (2) Organ chips and microphysiological systems[;] (3) Computer modeling[;] (4) Other nonhuman or human biology-based test methods, such as bioprinting[; and] (5) Animal tests.” Id. § 3209(a)(2) (enacting 21 U.S.C. § 355(z)).
[4] See, e.g., “The US Just Greenlit High-Tech Alternatives to Animal Testing,” Wired (Jan. 11, 2023).
[5] See, e.g., Sen. Cory Booker, Press Release, “Booker Urges FDA to Prioritize Non-Animal Testing Methods for Sunscreen Safety” (Dec. 16, 2024); “Rand Paul: Why Is the FDA Still Requiring Human or Animal Testing For New Drugs?,” Reason (Nov. 20, 2023).
[6] “FDA’s User Fee Programs at a Crossroads: User Fee Deadlines and Funding at Risk,” Gibson Dunn Biotech Briefings (Apr. 7, 2025); “FDA in Flux: What Life Science Companies Should Expect as the Agency Undergoes Staffing Changes,” Gibson Dunn Biotech Briefings (Mar. 4, 2025).