NAMs is a common acronym used to represent human biology-based methods in biomedical research. This acronym often refers to human-relevant testing methods like organ chips, organoids, and in silico models, but sometimes can include methods that are not human-relevant, but play a role in reducing the use of animals in testing. In the United States, the term NAMs is used to mean multiple different things including New Approach Methods or Methodologies, New Alternative Methods, Novel Alternative Methods, and Non-Animal Methods.
While each of these uses essentially represents the same thing, the uncertainty muddies the waters and creates a barrier to the work that is being done in this space. The inconsistent usage of “NAMs” prevents interested parties like those in related fields, policymakers, and the public from easily accessing available information on human-relevant testing methods.
Environmental Protection Agency
The Environmental Protection Agency (EPA) first began using the term “NAMs” in 2016 after the Frank R. Lautenberg Chemical Safety for the 21st Century Act amended the Toxic Substances Control Act (TSCA). This amendment contained provisions directing EPA to “promote the development and timely incorporation of alternative test methods or strategies that do not require new vertebrate animal testing.” On the heels of the Lautenberg Amendment, the EPA published the Strategic Plan to Promote the Development and Implementation of Alternative Test Methods Within the TSCA Program. This publication specifically determines that the acronym “NAM” refers to New Approach Methodologies and defines “NAMs” for the purposes of TSCA to mean “any alternative test method and strategies to reduce, refine, or replace vertebrate animals.” This definition does not require NAMs to be animal-free or specifically based on human-biology because it includes methods that reduce the number of animals used for tests or refine existing tests using animals in order to lessen or avoid the pain and distress these animals endure.
Food and Drug Administration
Unlike the EPA, the Food and Drug Administration’s (FDA) use of NAMs is not as clear-cut. The FDA uses NAMs to refer to both New Alternative Methodologies and New Approach Methodologies. In 2021, the FDA published a large report, Advancing New Alternative Methodologies at FDA. Both New Alternative Methodologies and New Approach Methodologies are used interchangeably in this report. Additionally, FDA publishes several slide decks discussing alternative methods at FDA where the NAMs acronym is used without a clear definition or “new approach methodologies” is used.
When searching for information on “NAMs” at the FDA, it is possible to locate a webpage titled “New Approach Methods (NAMs).” This webpage discusses the limitations associated with animal testing and the rise of methods to use in place of animal testing. Specifically referring to the methods to use in place of animal testing as new approach methods, but then later mentioning how these methods can be used to refine existing methods. The information this webpage provides reflects how EPA uses NAMs, but makes it less clear on whether NAMs at the FDA are also New Alternative Methods. Despite this webpage discussing how NAMs can be used to replace animal testing, it does not mention the other work FDA is doing on these methods including the New Alternative Methods Program and their larger publications.
The FDA provides resources to educate interested parties on alternative methods. While these resources can be very useful, when the term alternative methods is being defined as a “testing strategy that reduces or replaces the use of animal testing…” which does not specifically include strategies that “refine” test methods to make them less painful for animals while simultaneously stating that “alternative methods” are also called “new approach methodologies” which has included methods of refinement. It is hard for someone (especially who is not well versed in the specific methods) to fully understand what any of these terms mean or what methods are included under which term.
National Institutes of Health and Other Uses
The National Institutes of Health (NIH) introduces an additional level of confusion on NAMs. NIH has used NAMs to mean Novel Alternative Methods. In a February 9th post by Deputy Director for Extramural Research, Dr. Mike Lauer, he refers to NAMs as, not only, novel alternative methods, but also as “non-animal-based approaches.” This is a departure from terms used by both the EPA and FDA by also specifically noting that NAMs are non-animal methods. The Catalyzing the Development and Use of Novel Alternative Methods report was published late 2023. This report acknowledges that NAMs are sometimes defined as New Approach Methodologies, Non-Animal Methods, or New Alternative Methods. Furthermore, this report defined NAMs to include in chemico strategies, in vitro methods, and in silico computational models specifically. A past Request for Information put out by NIH used this definition of NAMs. This is a significant departure from other uses of NAMs as both EPA and FDA have not called NAMs Non-animal Methods.
While NIH seems to favor Novel Alternative Methods, other agencies that work with NIH use New Approach Methodologies including the National Institute of Environmental Health Sciences, the National Toxicology Program, and the Interagency Coordinating Committee on the Validation of Alternative Methods. In the Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) states that the term NAMs “has been adopted as a broadly descriptive reference to any non-animal technology, methodology, approach, or combination thereof…” This definition goes directly against how EPA and FDA have used the term to also include methods that lessen pain on animals including using non-mammal organisms such as Zebrafish.
What Next?
If you were confused reading the above section, you are not alone. The multiple recognized uses of “NAMs” combined with the inconsistent definition of those uses create confusion surrounding the methods to move away from animal testing. This confusion manifests itself in a significant way: what is a “NAM.”
Both the FDA and EPA leave the definition of NAMs open to include methods that reduce or refine the use of animals in testing, while the NIH specifically uses NAMs as methods that replace the use of animals in testing (and even sometimes refers to NAMs as Non-Animal Methods). This distinction can lead to someone interested in learning about Non-Animal Methods, on the basis that they do not agree that animals should be used in research, not having a clear idea of what methods do and do not use animals. Additionally, someone not well versed in this space may see calls for an end to animal testing and not be able to easily locate methods that are being used and developed to replace animals. This would be due to entities like the FDA and EPA not explicitly recognizing that NAMs are often Non-Animal methods in the manner of the NIH. Additionally, even those who work in this space do not have a clear understanding of what NAMs mean, as there are peer-reviewed publications using all versions of the NAMs acronym.
Multiple versions of the same acronym inhibit progress by creating unnecessary barriers for those interested in learning about innovative technologies that help us move away from animal testing. A challenge in this space is the confusion about what “alternatives” to animal testing exist––when those versed in this space are unable to use a consistent acronym or definition, it makes it increasingly difficult for newcomers to the field. A standardized definition for NAMs is critical to drive accessibility and education on human-relevant research.