by Joe Scimeca, TAG Senior Advisor
Co-author of Application of new approach methods (NAMs) in food safety with considerations for new proteins
Historically, research on the toxicity of a substance has amassed information through studies in which the substance is administered to animals and adverse impacts observed. But, given the limitations, costs, and ethical considerations involved in the use of animals, there has been increased focus by the scientific community on New Approach Methods (NAMs) as alternatives to traditional animal testing.
Fundamentally, NAMs are any method or approach that reduces or eliminates the need to conduct whole animal studies. This includes not only existing and emerging in-vitro and in-silico models, high-throughput screening, and predictive modeling, but also the reliance on historical databases of safe use.
Reducing Animal Testing in Preclinical Safety Studies Using New Approach Methods (NAMs)
To aid in the furtherance of NAMs, FDA recently published the Roadmap to Reducing Animal Testing in Preclinical Safety Studies outlining a strategic, stepwise approach for increasing the use of scientifically validated NAMs. In the roadmap, NAMs encompass a broad range of non-animal-based methods for assessing the safety of a substance, including in-vitro human-derived systems (organoids and micro-physiological systems, aka “organs-on-chips”); in silico tools and computational modeling; and other innovative technologies that can reduce or replace animal use.
While FDA’s roadmap is oriented toward use of NAMs for preclinical drug testing, there is no reason that NAMs can’t also be used to satisfy certain aspects of FDA’s regulatory testing requirements for ensuring the safety of food and feed ingredients and additives. In fact, in an October 2024 report (“Potential Approaches to Drive Future Integration of New Alternative Methods for Regulatory Decision-Making”), the NAMs Subcommittee of the Science Board to the FDA provided recommendations on how the agency can spur the broad adoption of NAMs, including “…as a possible way to drive faster and more accurate human risk assessments of compounds that FDA regulates (e.g., as drugs, food, cosmetics, and others…).”
FDA’s Role in Advancing NAMs for Food Safety
Among the subcommittee’s recommendations were that the FDA establish a transparent and scientifically rigorous review process for NAMs used to support product safety and/or efficacy product applications; identify and invest in high-impact NAMs initiatives that will aid in regulatory decisions; and compile a central NAMs database for all of FDA to use.
In May 2025, The Society of Toxicology released a statement on the use of animals in research and NAMs, and while supporting the principles of reducing, refining, and replacing the use of animals in science, the Society urged governmental agencies to “…maintain flexibility in their policies and language concerning methods used for safety and risk assessments.”
The Food Industry’s Role in Advancing NAMs for Ingredient and Protein Safety
The food industry has an equally important role of being an active partner with the FDA in advancing the use of NAMs by investing in NAM development, validation, and application to support safety and efficacy determinations. As pointed out in our paper, “Application of new approach methods (NAMs) in food safety with considerations for new proteins,” the increasing demand for new protein ingredients combined with limitations of animal models in assessing macronutrient safety provide incentive for the use of NAMs as an effective alternative.
Additionally, with the historical and scientific knowledge base for the source, structure, genetics, metabolism, toxicity, allergenicity and use having been well understood and documented for many types of proteins, the paper utilizes case studies of three categories of protein products to illustrate the application of NAMs: proteins produced by precision fermentation, protein concentrates from traditional foods, and total protein extracts.
Through this, NAMs can help determine protein safety by:
- Addressing mechanistic questions.
- Showing physicochemical equivalence to existing foods.
- Comparing intake levels to traditional consumption.
- Assessing potential allergenicity.
NAMs are well suited for identifying key safety concerns for a new protein, instead of relying on the traditional 13-week sub-chronic study, as a first step in identifying whether additional studies are needed. Demonstration of equivalence between a fermentation-derived protein and the existing corresponding protein can be achieved through the use of sophisticated analytical techniques such as mass spectrometry to assess whether any further toxicological testing is necessary. A determination can then be made on whether further safety studies are needed by comparing human exposure to new proteins with traditional consumption levels. Allergenicity can also be assessed by matching new proteins against established databases of known human allergens to ensure reliable results.
Implementing Public-Private Partnerships to Advance NAMs Adoption
The adoption of NAMs should continue to grow through short-term progress in their use, as well as the development of new techniques that have been scientifically validated. NAMs not only reduce reliance on animal studies but also offer the potential for greater sensitivity and specificity for assessing food components. But continued progress in their use depends on collaboration between the public and private sectors.
Summary: New Approach Methods (NAMs) are gaining momentum as validated alternatives to traditional animal testing, offering faster and more targeted ways to assess the safety of food ingredients and new proteins. As the FDA, researchers, and industry continue to advance and validate these tools, collaboration will be essential in supporting innovation while maintaining strong safety and regulatory confidence.
