FDA Modernization Act 2.0 Paves the Way to Computational Biology and Clinical Trials in a Dish
Open accessAbstract
The evaluation of drug safety and efficacy is an expensive, time-consuming process with a high failure rate.Animal testing was the only non-human testing method to assess drug safety and efficacy before clinical trials for nearly a century.The tragic incidents of mass poisoning that occurred when sulfanilamide was formulated into an elixir spurred the enactment in 1938 of the Federal Food, Drug, and Cosmetic Act that mandated all drugs must be tested for toxicity in animals and truthfully labeled 1 .In 1961, following the thalidomide disaster in other countries, the FDA enforced its own requirement for clinical trials and the need for preclinical validations of toxicity in animal studies.Since then, drug testing in animals has been the only standard recognized by the FDA before drugs are approved for human subject clinical trials.Following these guidelines, the success rate over the last 25 years of all drugs that entered Phase I clinical trials to reach FDA approval is only 9.6% 2 .Implicit in this failure rate is the inherent poor correlation between animal efficacy and toxicity data and how that adversely affected the success of drug approval in humans.This high failure rate necessitates the need for alternate methods to be instituted as part of the FDA approval process for clinical trials.On September 29, 2022, the U.S. Senate unanimously passed Bill S. 5002, which was subsequently approved by the U.S. House on December 23, 2022, giving rise to what is known as the "FDA Modernization Act 2.0".This landmark act is an attempt to update the 1938 mandate by allowing regulators to consider using new approach methods (NAMs) as a legitimate option to establish drug safety and efficacy instead of using animals.This bill allows the FDA to consider information other than animal studies, shining a spotlight on significant advancements in biology and technology over the past several decades.Some of these include cell-based approaches, such as human induced pluripotent
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This focus aligns with broader regulatory developments, as reflected in the FDA Modernization Act 2.0 and 3.0, which promote the adoption of Organ-On-Chip (OOC) platforms and other New Approach Methodologies (NAMs) as alternatives to traditional animal testing.
“This focus aligns with broader regulatory developments, as reflected in the Food and Drug Administration (FDA) Modernization Act 2.0 and 3.0, which promote the adoption of Organ-On-Chip (OOC) platforms and other New Approach Methodologies (NAMs) as alternatives to traditional animal testing (Carratt et al., 2024; Zushin et al., 2023; Ahmed et al., 2023).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as Ahmed et al., 2023
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Experimental — accuracy not yet measuredThe FDA Modernization Act 2.0 ends the long-standing animal mandate and promotes the use of validated in vitro human alternatives for next-generation drug development.
“Indeed, the recently passed FDA Modernization Act 2.0 ends the long-standing animal mandate and promotes the use of validated in vitro human alternatives for next-generation drug development.21”
From Reversal of contractile defects by mediating calcium homeostasis in human mini-heart models of heart failure with preserved ejection fraction (HFpEF) leads to first-in-human gene therapy clinical trial (2024) · cites this paper as [21]
In the paper’s discussion of the FDA Modernization Act 2.0 (page not specified), the authors say the act updates the animal-testing mandate by allowing regulators to consider alternatives, including human cell-based methods. The passage supports the shift toward in vitro methods for drug development, but does not say those alternatives have been validated. (LLM, conf=0.84)
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- Authors
- Ahmed, S. M., Shivnaraine, R. V., & Wu, J. C.
- Affiliations
- Stanford Cardiovascular Institute (US)
- Stanford Medicine (US)
- Venue
- Circulation
- Published
- 2023-07-25
- Volume
- 148
- Issue
- 4
- Pages
- 309-311
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC10902210
- OpenAlex
- W4385216125
- Cited by
- 46
- References
- 5
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 16 · 2023: 3
- FWCI
- 14.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R44HL170756)
- Topics
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Health Sciences › Medicine › Physiology › Biomedical Ethics and Regulation
- Health Sciences › Health Professions › Health Information Management › Healthcare Regulation
- Keywords
- new approach methodologies, alternatives to animal testing, drug safety assessment, computational biology, human induced pluripotent stem cells, drug approval, Federal Food, Drug, and Cosmetic Act
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