A coordinated national effort is emerging to bring alternatives to animal testing into routine preclinical use, backed by a fresh FDA roadmap and a global coalition of scientific and industry partners.
The Foundation for the National Institutes of Health (FNIH) will soon announce the first concepts for validation and qualification of New Approach Methodologies, Stacey Adam, vice president in science partnerships at the FNIH, told BioSpace in an interview. They will be developed into proof-of-concept projects for the long-term goal of expediting therapies to patients.
New Approach Methodologies (NAMs) are laboratory (in vitro or in chemico) or computer-based (in silico) research approaches that have the potential to transform basic, translational and clinical science through the development and use of new human-based biomedical research models.
NAMs will be further discussed on a Denatured podcast episode December 4.
“Many of the NAMs we select in the first few cycles will be more mature and well-validated,” Adam said. “Our goal is to push these toward acceptance and qualification by regulators. Over time, we may be able to bring forward more nascent technologies, providing additional validation as needed.”
Although NAMs have been in development for more than a decade, this year has seen the maturation of that long-term work, she continued. “The [FDA] has been advocating for alternatives to in vivo models through in vitro technologies for quite some time, but regulators naturally wait for sufficient evidence before fully embracing new approaches,” she said.
But the agency’s publication in April of the Roadmap to Reducing Animal Testing in Preclinical Safety Studies indicated the FDA’s renewed drive in NAMs engagement, agreed Adam and Patrick Smith, senior vice president of Translational Science at Certara.
“This roadmap outlines a strategic, stepwise approach for FDA to reduce animal testing in preclinical safety studies with scientifically validated [(NAMs)], such as organ-on-a-chip systems, computational modeling, and advanced in vitro assays,” the document states. By partnering with federal agencies like the National Institutes of Health and Veterans Administration through the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), “FDA can accelerate the validation and adoption of these human-relevant methods, improving predictive accuracy while reducing animal use.”
Companies are weighing the pros and cons of being the first to undergo the validation process, Smith said. Large pharma may have an advantage because their broad portfolios give them the flexibility to run pilots and test new approaches, and more are developing organ-on-a-chip methods internally and actively incorporating them into their programs, he added.
“On the other side, we’re hearing from many biotechs saying, ‘Does this mean we no longer need [animal] toxicity studies? How can we move faster?” Smith noted.
The roadmap drew heavily from an ICCVAM report issued in 2024, Adam said. “Currently, [the FNIH and the NIH] are in the design phase of the Validation Qualification Network (VQN), defining the overarching infrastructure for long-term implementation.” VNQ’s partners, including Certara and others at the table, are helping shape this design, she added.
The FNIH intentionally maintained a “large tent” to gather a wide range of perspectives during the design phase, including international engagement, ensuring that stakeholders could provide input and help guide the pilot program, Adam said.
On the federal side, about 15 agencies are participating, with the FDA and EPA being the most prominent. From the private sector, there are more than 40 partners ranging from small methods developers to companies like Certara, which help advance NAMs, as well as end users including pharma companies, chemical companies represented by the American Chemistry Council, and nonprofits invested either in NAM development or in reducing animal use.
European Commission observers, Japanese regulators and representatives from several ministries in India all have seats at the table, and further international engagement is under discussion, Adam said.
The VQN will define shared data elements and unify reporting practices across preclinical, clinical and safety testing. Alongside the VQN, the program also includes Technology Development Centers and the NAMs Data Hub and Coordinating Center.
As part of the Data Hub and Coordinating Center, there will also be a searchable database of NAMs, Adam said, including their validation status and which organizations are actively participating. This will help provide transparency and foster collaboration across the field.
The Scientific Rationale
NAMs are increasingly considered a suitable alternative to toxicology studies, which are typically long, resource-intensive programs involving large numbers of animals, Adam said. There is growing scientific recognition that animals do not provide adequate models of human health and disease, the roadmap states.
“If technologies like microphysiological systems or organ-on-a-chip platforms can replace what is currently a multi-month process—administering drugs to animals, then dissecting tissues to understand effects—that would be transformative,” Adam said. “These systems can generate insights in days or weeks, so I think toxicology and safety will be among the first areas where NAMs gain widespread deployment.”
Areas with high activity and obvious impact, like liver and cardiac toxicity, will be well- represented in the NAMs portfolio. “At the same time, we’re emphasizing areas of unmet need, such as ocular and neurological applications, where development is less advanced,” she said.
In terms of therapeutic areas ripe for deployment, Adam pointed out that organoid models, multicellular chips and related technologies have been used in cancer research for quite some time across academic labs, biotech and likely pharma as well.
“Of course, everything depends on the interest and funding from our partners,” Adam said, adding that FNIH is also selecting pilot proof-of-concept projects that can realistically be implemented.
“One reason oncology moved in this direction early is its alignment with personalized medicine. Researchers can take a patient’s tumor, create organoids or chip-based systems directly from it, and then test drugs against that patient’s own cancer,” Adam said. “This offers a higher-throughput, in vitro alternative to traditional xenograft models and enables more tailored treatment strategies when feasible.”
The roadmap suggests starting with monoclonal antibodies (mAb) as a promising area for reducing animal use in preclinical safety testing and then expanding to include other biological molecules and eventually new chemical entities and medical countermeasures. The mAbs selection makes sense, Smith said, as they have more predictable pharmokinetics and less off-target effects than small molecules.
Validation Crucial for Widespread Adoption
For a company to routinely adopt these approaches or include them in a preclinical submission, it needs to have confidence that the technology is thoroughly validated, Adam said. “That means strong technical validation, ideally replicated across multiple laboratories, so companies know the method is robust, reproducible and capable of generating data they can trust.”
Microphysiological systems are relatively far along, largely because they’ve received substantial investment from both pharma and government, she said. For example, the National Center for Advancing Translational Sciences at the NIH has supported a major portfolio focused on organ-on-a-chip development.
Still, the field still faces significant gaps. “There’s limited standardization, limited advanced validation, and none of these technologies have yet been qualified through FDA programs like the Innovative Science and Technology Approaches for New Drugs (ISTAND) program,” Adam said.
Take organ-on-a-chip technologies, for example. Imagine five different labs each with a “heart-on-a-chip” system; they may use slightly different cell lines or flow parameters. The goal is to reach a point where those minor differences do not affect standardized readouts, which should reliably replicate what is seen in animals or humans, Adam noted.
From the industry viewpoint, demonstrating a clear, workable regulatory path with valid systems is critical, and that can only be done once robust systems are in place, Smith said.
Closing this gap is a central objective of the VQB public–private partnership. The effort aims to thoroughly validate these methods and produce enough supporting evidence for regulators to confidently incorporate them into preclinical submissions.
As part of this regulatory package, alignment with international regulators is a key consideration to facilitate this field and product development, Adam and Smith agreed. Europe and Australia are ahead of the U.S. regarding NAMs, with a greater openness to accepting these methodologies, and have actively pushed these initiatives forward faster than the U.S.
“The path forward will require combining better assays and methodologies with AI and in silico modeling,” Smith said. “Together, these approaches can drive meaningful progress. Until then, we are likely in a position to significantly reduce animal use, even if complete elimination is not yet feasible.”
