The U.S. Food and Drug Administration released on Mar. 24 a draft guidance aimed at helping drug developers validate new approach methodologies (NAMs) that could replace traditional animal testing in regulatory submissions.
The new document is intended to clarify how companies can use NAMs, which include complex and two-dimensional in vitro studies, as well as in chemico and in silico methods, to generate evidence of a molecule’s effects without using animals. This move is seen by experts as an important step toward reducing regulatory uncertainty for companies considering non-animal testing approaches.
Michael Phelan, principal consultant at InnovApproach Consulting, said the guidance “sends a clear signal that FDA is serious about integrating NAMs into [investigational new drug] submissions.” He added that while the FDA has previously discussed these concepts informally, putting them into official documentation lowers perceived regulatory risk and encourages proactive use of NAMs: “It helps close the gap between what FDA has been saying informally and what sponsors feel comfortable submitting.”
Steven Bulera, chief scientific officer for discovery and safety assessment at Charles River Laboratories, said the draft provides “an additional layer of regulatory clarity” that enables researchers to show NAMs can produce “reliable, reproducible, human-relevant data that answer specific regulatory questions.” Kevin Snyder from Certara noted that although previous programs like ISTAND offered a path forward for NAM validation since 2020, the process was "fairly laborious." Snyder said the new draft does not introduce novel pathways but represents significant progress: “Sponsors now know what information they will need to justify NAM use and can factor that end goal into the designs of their programs from day one.”
A key element highlighted by experts is the importance of defining context of use (COU) for each NAM submission. COU specifies how a methodology will be used within drug development or regulation. Phelan emphasized its significance: "The importance of COU cannot be overstated." According to Bulera and Snyder, initial uses may focus on interpreting results from animal tests rather than replacing them outright.
Health Secretary Robert F. Kennedy Jr. stated that ultimately "the goal is to replace animal testing with human-relevant, scientifically rigorous methods," though Bulera described this transition as evolutionary rather than revolutionary. The FDA will accept feedback on its draft guidance until May 18.
