For nearly 84 years, the US Federal Food, Drug and Cosmetic Act has demanded that any drug intended for humans be tested in animals before human clinical trials commence. If Congress passes a package of reforms for the Food and Drug Administration as expected, that mandate could be reversed this summer. The legislation does not ban animal testing. Instead, it allows the use of alternatives — such as organ-chips that recreate the physiology of the human body in a microchip — that are claimed to be better than animal models for evaluating drug safety and effectiveness in humans.
The lead sponsor of the FDA Modernization Act of 2022, Rep. Vern Buchanan of Florida, said in a press release. “Our drug development model needs a reboot, and this bill moves us in that direction in one simple but meaningful way. Generally, animal tests do not predict the human response to drugs, with very high failure rates when the drugs go to clinical trials.”
Introduced as standalone bills in the House and Senate, the FDA Modernization Act was later included in both chambers by health-committee leaders as amendments to broader FDA-related statutory packages. These larger bills are considered must-pass beas they contain provisions that update and reauthorize user fees paid by pharmaceutical companies that account for 45 per cent of the FDA’s budget. If the fees are not reauthorized by mid-August, the agency could start to send out unemployment notices to employees. The previous authorization expires on September 30, 2022.
On June 9, bipartisan solid support carried H.R. 7667 through the House by a vote of 392 to 28. Then on June 14, the related Senate Bill, S. 2952, cleared the Senate Health, Education, Labor and Pensions Committee by a vote of 13 to 9.
Many animal welfare groups, biotech companies, medical associations and patient advocacy organizations have supported the bills. Wayne Pacelle, founder and president of the Animal Wellness Action, a major animal rights lobby group and an advocate of the FDA Modernization Act, said the strength of the legislation is that what is right for animals is also right for the public’s health.
“Between 90 per cent and 95 per cent of drugs shown safe in nonclinical tests do not succeed during human clinical trials because of toxicities not predicted by animal tests or because of lack of efficacy,” Pacelle said. “Those failures hinder research, extend time frames, increase costs for drug developers and disincentivize research on drugs for rare conditions. Embracing new, non-animal test methods, will speed development timelines, provide more reliable results and lower failure rates.”
Bill supporters also consider removing the animal-testing requirement will encourage more development of human-based biological alternatives such as organ-chips and promote greater recognition of what Pacelle calls “morally and scientifically superior” testing methods.
The legislation follows developments at the FDA, which has been spending more money on resources and pursuing research into alternatives that reduce the need for experimental animals or their numbers.
The FDA’s budget application for the fiscal year beginning October 1 includes funding for a wide-ranging strategy of product-testing alternative methods “… to decrease animal testing by developing qualified alternative techniques and stimulate the acceptance of methods for regulatory use that can replace, reduce and refine animal testing.” The “replace, reduce and refine” are well known in laboratory animal medicine as the 3Rs. They are a humane basis for experimentation in animals developed by William Russell, a zoologist, and Rex Birch, a microbiologist, in the 1950s. Since then, they have been widely adopted by academia, industry and government. Precisely, the 3Rs are Replacement: circumventing or replacing the use of animals, for example with in-silico models such as computer modeling or computer simulation; Reduction: using as few animals as possible to get enough necessary data; and Refinement: changing husbandry and techniques to experimental animals’ pain and distress.
Under existing FDA rules, it is impossible to escape from using animals altogether. According to Pacelle, no definitive count of animals used in drug testing each year. Some species, such as mice and rats, do not have to be tallied, and those that are counted are not classified by the type of testing, such as drug development versus testing chemicals or cosmetics.
“Some people would like to see a ban on animal testing,” Pacelle said. “We decided not to push for that because animal testing has been the paradigm for a long time, and drug developers and regulators need to transition over time from that strategy. Enlarging human-based biological testing systems will go a long way toward reducing the number of animals used in experiments, even without a ban.”
The two FDA reform packages differ in some terms, so after the Senate passes its version, it will need to be resolved with the House version. Some elements may disappear or be revised from the final bill. Pacelle said it is unlikely the testing provision would be jettisoned since the language is similar in both bills and has broad support.