Title: The FDA Modernization Act 2.0: Drug Testing in Animals is Rendered Optional
Abstract: The FDA Modernization Act 2.0 (S.5002), a bipartisan bill co-authored by Senators Cory Booker (D-NJ) and Rand Paul (R-KY), was passed by the U.S. Senate on September 29, 2022, by unanimous consent and without amendments. Later ratified by the US House of Representatives, the FDA Modernization Act 2.0, now part of the Consolidated Appropriations Act, 2023, was enacted into law on December 29, 2022.1CONGRESS.GOV. H.R.2617 - Consolidated Appropriations Act, 2023. Became Public Law No: 117-328. December 29, 2022. Available at: https://www.congress.gov/bill/117th-congress/house-bill/2617/text. Accessed March 10, 2023.Google Scholar The new law amends the Federal Food, Drug, and Cosmetic Act by authorizing sponsors of novel drugs to make use of “certain alternatives to animal testing, including cell-based assays and computer models, to obtain an exemption from the Food and Drug Administration to investigate the safety and effectiveness of a drug.”1CONGRESS.GOV. H.R.2617 - Consolidated Appropriations Act, 2023. Became Public Law No: 117-328. December 29, 2022. Available at: https://www.congress.gov/bill/117th-congress/house-bill/2617/text. Accessed March 10, 2023.Google Scholar The new law also “removes a requirement to use animal studies as part of the process to obtain a license for a biological product that is biosimilar or interchangeable with another biological product.”1CONGRESS.GOV. H.R.2617 - Consolidated Appropriations Act, 2023. Became Public Law No: 117-328. December 29, 2022. Available at: https://www.congress.gov/bill/117th-congress/house-bill/2617/text. Accessed March 10, 2023.Google Scholar In this Commentary we review the history of legislative efforts to curtail the mandated use of animals in the testing of drugs for safety and efficacy, discuss the emergence of nonanimal drug testing technology, and review the future prospects thereof. Congressional expressions of concern over the reliance of the US Food and Drug Administration (FDA) on animals for safety and efficacy testing have been a matter of record since 1998. It was in the course of hearings of the Senate Committee on Appropriations that the Doris Day Animal League lamented the discontinuation of “all assessments of in vitro, or non-animal test methods, to substantiate the safety of products.”2Authenticated US Government Information (GPO). Hearings Before a Subcommittee of the Committee on Appropriations. 105th Congress. Prepared Statement of Sara Amundson, Doris Day Animal League. March 31, 1998. Available at: https://www.govinfo.gov/content/pkg/CHRG-105shrg46086/pdf/CHRG-105shrg46086.pdf. Accessed March 10, 2023.Google Scholar Congressional consideration of the authorization of an Interagency Coordinating Committee on the Validation of Alternative Methods followed suit before too long. However, it was not until 2019 that a flurry of Congressional bills were introduced with an eye toward limiting the use of animals in the testing of new drugs on humane grounds. Examples include, but are not limited to, the Reducing Animal Testing Act (S.4288), a bill introduced by Senator Ben Ray Lujan (D-NM) on May 19, 2022. Perhaps the most compelling illustration of the leanings of the Senate is illustrated by the “Sense of the Senate on Animal Testing” the central missive of which was that “animal testing should not be used for the purposes of safety testing on cosmetic products and should be phased out with the exception of appropriate allowances.”3CONGRESS. GOV. S.2100 - Personal Care Products Safety Act. SEC. 109. Sense of the Senate on Animal testing. June 17, 2021. Available at: https://www.congress.gov/bill/117th-congress/senate-bill/2100. Accessed March 10, 2023.Google Scholar Now comprising Section 3209 (Animal Testing Alternatives) of the Consolidated Appropriations Act, 2023, the FDA Modernization Act 2.0 amends Section 505 of the Federal Food, Drug, and Cosmetic Act, which mandates animal toxicity testing of novel drugs prior to their deployment in human subjects in the course of clinical trials.1CONGRESS.GOV. H.R.2617 - Consolidated Appropriations Act, 2023. Became Public Law No: 117-328. December 29, 2022. Available at: https://www.congress.gov/bill/117th-congress/house-bill/2617/text. Accessed March 10, 2023.Google Scholar Specifically, the newly enacted law replaces the statute's reference to “preclinical tests (including tests on animals)” with “nonclinical tests” that are to be “conducted in vitro, in silico, or in chemico, or a nonhuman in vivo test, that occurs before or during the clinical trial phase of the investigation of the safety and effectiveness of a drug.”1CONGRESS.GOV. H.R.2617 - Consolidated Appropriations Act, 2023. Became Public Law No: 117-328. December 29, 2022. Available at: https://www.congress.gov/bill/117th-congress/house-bill/2617/text. Accessed March 10, 2023.Google Scholar Such tests may include the following: “(1) Cell-based assays, (2) Organ chips and microphysiological systems, (3) Computer modeling, (4) Other nonhuman or human biology-based test methods, such as bioprinting, and (5) Animal tests.”1CONGRESS.GOV. H.R.2617 - Consolidated Appropriations Act, 2023. Became Public Law No: 117-328. December 29, 2022. Available at: https://www.congress.gov/bill/117th-congress/house-bill/2617/text. Accessed March 10, 2023.Google Scholar In noting the significance of the new law, Senator Booker offered that it “will avoid the needless suffering of countless animals, now that experimental drug testing can be done with modern non-animal alternatives that are more scientifically relevant.” Senator Paul, for his part noted that “this bipartisan effort is a step toward ending the needless suffering and death of animal test subjects … will accelerate innovation and get safer, more effective drugs to market more quickly by cutting red tape that is not supported by current science.” Inasmuch as the institution of animal-free drug testing for efficacy and safety constitutes a worthy goal, the all-out realization of this lofty objective may not be quite at hand as yet. As it now stands, the FDA requires toxicity tests on one rodent species (eg, mouse or rat) and one nonrodent species (eg, nonhuman primate or canine). Alternative in vitro modes for drug testing have made frequent use of cell-based assays in multi-well plates. Evolving substitutes such as “organ-on-a-chip” technology (micro physiological system), seek to simulate the in vivo state by passing the soluble drug under study through living cell-lined interconnected channels that are embedded in silicone-based polymers. Use also has been made of organoids, that is, miniaturized 2- or 3-dimensional assemblies of cells, which, as a rule, are derived from induced pluripotent stem cells. Finally, consideration is being given to digital artificial intelligence and machine learning in drug screening, replete with an emphasis on assessing toxicity. Important as the aforementioned technologies are to be deemed, the science in question remains a work in progress, the routine implementation of which has yet to be realized. The aforementioned Congressional initiatives reflect a larger world-wide drive to minimize or eliminate the reliance on animals for drug testing that has been underway for some time. It was 2014 when the United Kingdom announced plans to minimize the use of animal tests in scientific research with an eye toward replacing those tests with “scientifically valid alternatives” where and when possible. More recently, in 2021, the European Parliament voted overwhelmingly in favor of a resolution that calls on the European Commission to draw up an action plan to phase out animal experiments. The United States is now following suit. Leading the way is the Environmental Protection Agency, which became the first federal agency to commit to phasing out all testing of mammals by 2035. More of the same is taking shape at the FDA, wherein the Alternative Methods Group is in continuous pursuit of “useful tools as well as new areas of science to support alternative methods to traditional toxicity and efficacy testing that extend across FDA's product areas.”4U.S. Food & Drug Administration. Advancing alternative methods at FDA. January 5, 2022. Available at: https://www.fda.gov/science-research/about-science-research-fda/advancing-alternative-methods-fda. Accessed March 10, 2023.Google Scholar As seen by the US Congress, the passage of the FDA Modernization Act 2.0 is but an added incentive to an animal-sparing federal drive that appears to be well underway. It is not beyond the realm of possibility that more of the same will apply to federally funded research. Indeed, H.R.1024, a bill introduced by Rep. Chris Pappas [D-NH-1] as recently as February 14, 2023, seeks to amend the Public Health Service Act to ensure that “non-animal methods are prioritized, where applicable and feasible, in proposals for all research to be conducted or supported by the National Institutes of Health, and to provide for the establishment of the National Center for Alternatives to Animals in Research and Testing, and for other purposes.“5CONGRESS.GOV. H.R.1024 – HEARTS Act of 2022. To amend the Public Health Service Act to ensure that nonanimal methods are prioritized, where applicable and feasible, in proposals for all research to be conducted or supported by the National Institutes of Health, to provide for the establishment of the National Center for Alternatives to Animals in Research and Testing, and for other purposes. February 14, 2023. Available at: https://www.congress.gov/bill/118th-congress/house-bill/1024?s=1&r=1. Accessed March 10, 2023.Google Scholar The next several years are likely to prove decisive as to how far Congress is willing to go in curtailing the use of animals, not least of which in the context of federally funded basic science research.