NAMs in Industry: FDA Shows Emerging Trends in Regulatory Submissions

By Jorge Gana | May 7th, 2026

After decades of development, new approach methodologies are slowly breaking into the treatment development pipeline.

For players in the life science industry, new approach methodologies (NAMs) offer huge upsides in preclinical research, but they come with regulatory uncertainty. NAMs encompass alternatives to whole animal models used for testing the safety and efficacy of drugs. They can offer better predictivity of human trials while cutting costs and timelines. Still, traditional animal models have stronger precedent in FDA decision-making than NAMs, and when rejected regulatory submissions can delay treatment access or sink billion-dollar investments, industry sponsors find themselves cautious to test new methods for demonstrating a treatment candidates’ safety and toxicology profile. This paradigm is changing… gradually.

Prevalence in Industry

In a new 2025 publication, the FDA’s Center for Drug Evaluation Research (CDER) offers data on how often NAMs appear in regulatory submissions to the agency. This data signals the beginnings of NAM utilization in industry and exemplifies a regulatory transparency that can drive further investment from sponsors. Below are some key highlights:

• New approach methodologies have been included in only <1% of Investigative New Drug applications (INDs), New Drug Applications (NDAs), and Biologics License Applications (BLAs) from the last 15 years.

• in vitro and in silico techniques comprise 93% of non-animal alternatives used in all INDs, NDAs, and BLAs from the last 15 years.

• Submitted in vitro techniques are predominantly stem cell-derived models (42%), followed by sandwich cultures (21%), co-cultures (19%), then 3D culture models (11%).

• Submitted in silico techniques were found only from general keywords: “in silico” (66%) and “Quantitative Structure Analysis” or “QSAR” (33%).

With new data, the FDA offers several insights for translational researchers. Take organ-on-a-chip models and microphysiological systems: these methods have received significant praise and interest but only comprise 13 of 1178 instances of in vitro NAMs in submissions. That machine learning and artificial intelligence appeared nowhere in the submission data is even more striking. These examples highlight that translational research and validation efforts for some promising models have not been sufficient for industry adoption. As such, the FDA advises better resource allocation to researching these NAMs.

The observed trends also yield needed benchmarks for past policies. The 2022 passage of the FDA Modernization Act 2.0 and FDORA specifically allows in silico, in vitro, and in chemico approaches in place of animal testing requirements. However, data here shows fewer than 1% of CDER regulatory submissions include any such NAM in the last 15 years. Furthermore, the FDA adds that no significant increase has been observed since 2022. The 2025 FDA Modernization Act 3.0 and the NAMs Roadmap are actions already taken to address possible weaknesses in past policies, but more time is needed to judge their effectiveness.

In the meanwhile, the FDA calls on industry sponsors for help. “With increased NAMs submissions to CDER in drug development packages,” the authors write, “sponsors, and regulators together, can build scientific confidence on the use of NAMs to improve drug development”. Parallel submissions of NAMs and traditional models together and using keywords in NAM study reports (to aid future data collection) are other FDA recommendations to sponsors.

Impact in Industry

Even with such low prevalence, there are already instances of NAM studies being used to help treatments reach patients faster. Another 2025 paper from FDA highlights several:

• Kalydeco: In 2017, the FDA expanded Kalydeco’s approval to additional cystic fibrosis variants based on an in vitro cell-based model, without a specific post-approval trial.

• Galafold: After the drug’s initial 2018 approval, an in vitro assay was accepted as evidence for effectiveness in GLA gene variants of Fabry disease. The NAM data was later confirmed as predictive of the subsequent post-approval trial.

• Veopoz: Its 2023 approval for Chaple disease used cytotoxicity, hemolysis, and other efficacy data from a CH50 ex vivo cell assay. This data proved critical in the context of an extremely small patient population and lack of disease-relevant animal models.

• Kimmtrak: The drug’s 2022 approval was supported by toxicity and off-target reactivity data from a human tissue-based in vitro assay. The assay justified safety endpoints used in clinical trials, and predicted efficacy in patients with uveal melanoma.

Looking Forward

The industry pressures to better predict clinical success, cut down development costs, and shorten timelines have long been present. Since NAMs contribute to all of these goals, why the slow adoption?

Industry change is gated both by government regulation and scientific development. Even with formal acknowledgement of NAMs in the FDA Modernization Act 2.0 and the added reforms/incentives in the act’s successors, industry adoption is capped by the speed of translational research. Nonetheless, examples like Kalydeco, Galafold, Veopoz, and Kimmtrak demonstrate real patient benefit and real economic incentive to adopting these approaches in industry; research and validation efforts must be funded and incentivized. Commitments to open science, continued funding of NAM research, and first-hand participation in NAM development are all steps industry leaders can take to ensure that technology meets the demands for new and validated, nonclinical testing.

References

Avila, Amy M et al. “An FDA/CDER perspective on nonclinical testing strategies: Classical toxicology approaches and new approach methodologies (NAMs).” Regulatory toxicology and pharmacology : RTP vol. 114 (2020): 104662. doi:10.1016/j.yrtph.2020.104662

Carratt, Sarah A et al. “An industry perspective on the FDA Modernization Act 2.0/3.0: potential next steps for sponsors to reduce animal use in drug development.” Toxicological sciences : an official journal of the Society of Toxicology vol. 203,1 (2025): 28-34. doi:10.1093/toxsci/kfae122

Dao, Tyna, and Nakissa Sadrieh. “A CDER perspective: Landscape of New Approach Methodologies (NAMs) submitted in drug development programs.” Regulatory toxicology and pharmacology : RTP vol. 165 (2026): 106007. doi:10.1016/j.yrtph.2025.106007

Han, Jason J. “FDA Modernization Act 2.0 allows for alternatives to animal testing.” Artificial organs vol. 47,3 (2023): 449-450. doi:10.1111/aor.14503 

Harrell, Andrew W et al. “Endeavours made by trade associations, pharmaceutical companies and regulators in the replacement, reduction and refinement of animal experimentation in safety testing of pharmaceuticals.” Regulatory toxicology and pharmacology : RTP vol. 152 (2024): 105683. doi:10.1016/j.yrtph.2024.105683

Shenton, Jacintha et al. “Opportunities and insights from pharmaceutical companies on the current use of new approach methodologies in nonclinical safety assessment.” Drug discovery today vol. 30,4 (2025): 104328. doi:10.1016/j.drudis.2025.104328

Yao, Jia et al. “FDA/CDER/OND Experience With New Approach Methodologies (NAMs).” International journal of toxicology, 10915818251384270. 13 Nov. 2025, doi:10.1177/10915818251384270

The views expressed do not necessarily reflect the official policy or position of Johns Hopkins University or Johns Hopkins Bloomberg School of Public Health.