Impact on Product Development: FDA Phasing Out Animal Testing Requirement

Contributing Author: Hema Balasubramanian

The FDA announcement on its plan to phase out the requirement for animal testing (3Rs principle) has been in development and saw increased interest from sponsors after the 2022 FDA Modernization Act 2.0 introduced the possibility of non-animal alternatives. FDA’s Roadmap to Reducing Animal Testing in Preclinical Safety Studies highlights the Agency’s thinking on this approach and clearly notes that this will be a staged approach which will allow data to be collected, reviewed, and assessed to aid in the assessment of risk to patients in phasing out animal studies.  

The program will initially focus on monoclonal antibodies which already have reduced nonclinical safety testing for first-in-human safety studies under ICH S6. The FDA will look to use New Approach Methodologies (NAMs), which may consist of In Vitro derived systems such as organs-on-chips, computational modeling and artificial intelligence, and other innovative platforms such as assessment in ex vivo human tissue. During the next three years to implement the transition from animal studies to NAM-based approaches, the FDA aims to review pre-existing data, work with sponsors to implement NAM based studies, develop an open access data repository on drug toxicity, reduce the routine six-month non-human primate (NHP) testing to three months if accompanied by NAM data. FDA will also look to implement these changes in other drug modalities, while quantifying how these changes may impact drug development. FDA also plans to provide regulatory incentives for companies that submit strong safety data from nonanimal tests. 

While the changes are significant, they are also in development, and interactions with the Agency will be necessary for sponsors looking to incorporate this approach. The FDA notes the need to develop critical endpoints, support targeted development of NAM technologies, and the need to collaborate with the National Institutes of Health (NIH) and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) on the development, validation, and qualification of NAMs. The collection and development of this data will be critical to help drive new Agency guidances that sponsors will rely upon to pursue this approach.  

Halloran will be assessing how the recent funding impacts to NIH and research institutes, and staffing changes at the Agency impact the development of the NAM approach and the associated guidances.  

For clients who are interested in pursuing the use of a NAM for product development, the current lack of specific guidance means interaction with the Agency early on will be essential. Sponsors will need to understand potential impacts based on their indication and a NAM approach, and if they can account for all aspects of a nonclinical package (i.e., CNS Safety Pharmacology studies) or if animal studies may still be necessary. Additionally, sponsors should consider that the Agency’s openness to NAM may not just be limited to initial Investigational New Drugs (INDs) but may also serve to address concerns raised by the Agency for an established nonclinical package. While FDA notes an intention to drive adoption with other global regulatory agencies, sponsors will need to assess other regulatory agencies and how ex-US adoption of NAMs may impact a product’s development outside of the United States.  

The NAM approach is a significant step forward recognizing the limitations of animal testing for certain product modalities, and a potential to bring products to clinical trials in a faster and more efficient manner.