From Concept To Confidence: A Collaborative Path To Validating NAMs
By Ray Dogum, Chief Editor, Drug Discovery Online
As the biomedical research landscape evolves, drug discovery companies are increasingly exploring alternatives to traditional animal models.
A key milestone in this shift came on August 1, 2025, when the Foundation for the National Institutes of Health (FNIH) released a Request for Information (RFI) inviting proposals for pilot projects under the newly launched Validation Qualification Network (VQN). This initiative is part of the broader Complement-ARIE program (established in 2024), which aims to accelerate the development, validation, and regulatory acceptance of New Approach Methodologies (NAMs).
NAM Concept Submission Timeline
For companies developing or deploying NAMs—such as organoids, microphysiological systems (MPS), and computational models—the RFI offers a structured opportunity to engage in precompetitive, multi-stakeholder projects that could shape future regulatory standards.
The timeline outlined in the RFI provides clarity for planning:
- August 31, 2025: First cycle application deadline
- September 30, 2025: Notification of selected concepts from the first cycle
- December 31, 2025: Final deadline for rolling submissions
Selected concepts will be developed into collaborative pilot projects during the Implementation Phase, which spans Years 2–6, with a possible extension through Years 7–11. The initial Design Phase (Year 1) focuses on building partnerships, defining governance, and selecting up to four pilot projects. Another four may be selected during the implementation period, depending on community engagement and support.
A Strategic Opportunity for NAM Developers
“This is new,” says Stacey Adam, PhD, who leads the VQN initiative. She explained to me how, “We’re trying to figure out how to work these types of projects in a pre-competitive space.” For drug developers, participating in this process offers not only scientific collaboration but also the potential to co-develop regulatory-grade NAMs aligned with FDA and NIH priorities.
This is a huge opportunity for NAM developers to establish a heavy footprint in the marketplace. By contributing to early pilot projects, companies can help shape the standards and expectations for NAMs, positioning themselves as leaders in a space that’s rapidly gaining momentum.
Measuring Community Interest
While the NIH has not publicly defined its metrics for reducing animal use, the VQN has its own framework. “We’ll be tracking how many of our projects are NAM-only, how many use traditional models for comparison, and how many of our methodologies are able to replace animals,” Adam explains. This data-driven approach is essential for demonstrating progress and guiding future investments.
Pilot proposal submissions must meet specific criteria and will be evaluated based on about a dozen factors including the Context of Use (CoU), Domain of Applicability (DoA), relevance to human biology, and whether the concept proposes a combination of NAMs (which is highly encouraged but not required). According to Adam, as of August 13th, 2025, there have not been any official submissions, but interest has been strong. “I’ve had probably close to 40 or 50 emails of questions,” Adam shares. “We’re guessing maybe we can expect 30 to 40 submissions.”
Importantly, the interest spans both academia and industry. “I think it's going to be split down the middle between academic groups and companies, so we shall see,” says Adam.
Regulatory Pathways: Big Q vs. Little Q
One of the most significant hurdles for NAMs is regulatory qualification. In the U.S., the FDA’s ISTAND program offers a pathway for official qualification—referred to as “Big Q.” However, as Adam points out, “There hasn’t been a NAM that’s been fully through the ISTAND program yet, but I know it's a high priority of the current FDA commissioner to begin to see those things move through more quickly.”
That doesn’t mean NAMs lack regulatory value. Many are considered “little Q” qualified, meaning they’ve demonstrated sufficient evidence to be accepted by regulators without formal designation. “Sometimes it just needs enough validation, enough repetitive kind of use across laboratories,” Adam says. “Regulators come in multiple shapes and sizes… and they all have slightly different parameters.”
This nuanced view aligns with the FDA’s evolving stance, as highlighted in my previous article “FDA Leading the Decline of Animal Testing.” The agency is actively exploring alternatives and has signaled a willingness to accept NAM-generated data under certain conditions.
Decades in the Making
Despite being labeled “new,” many NAMs have been in development for over a decade. “We’re not transitioning to technologies that are not understood or that are not well developed,” Adam emphasizes. “These are things that people have been working on. It’s taken a lot of time to get them to this space.”
This sentiment echoes the message in “The Rise of NAMs", which outlines how organoids, organ-on-chip systems, and computational models are gaining traction due to their ability to mimic human biology more accurately than animal models.
Indeed, some NAMs are already demonstrating remarkable capabilities. Adam describes systems where “fibroblasts, vascular cells, immune cells, and tumor cells” are combined in spheroid formats within multi-well plates. “You could take cells… and recapitulate a person’s tumor and microenvironment in vitro. Then test 1,000 compounds against that in a week’s time.”
Preparing the Next Generation of Researchers
As NAMs gain momentum, young scientists must also adapt. Adam advises staying current with emerging technologies and integrating them into your research. Training and education are central to the VQN’s mission. “We want scientists to begin adopting these methodologies,” Adam says. “Once they’re done at scale… they’re going to be so much more inexpensive than maintaining mouse colonies.”
This shift could democratize research, making advanced testing more accessible and personalized. “NAMs will be much more amenable to taking the precision medicine approach,” Adam notes.
Trust Through Transparency
Ultimately, the success of NAMs depends on trust—among scientists, regulators, and the public. “We want to engage the public,” Adam says. “We want to advance forward from what we’ve seen in the past, where the public doesn’t always trust new technologies very quickly.”
Transparency, collaboration, and rigorous validation are the pillars of that trust. Through initiatives like the VQN, the scientific community is laying the groundwork for a future where NAMs are not just accepted, but expected.