An opportunity for organoid! FDA no longer requires preclinical animal testing of drugs

Under a bill signed by President Joe Biden in late December 2022, new drugs would not need to be tested on animals to be approved by the U.S. Food and Drug Administration (FDA). Animal rights advocates have long pushed for the move, with pharmaceutical industry sources arguing that animal testing can be inefficient and costly. The move marks a major shift in the use of animals after more than 80 years of drug safety regulation.

The Act repeals the 1938 regulation requiring prospective drugs to be evaluated in animals for safety and efficacy, and it permits the FDA to advance pharmaceuticals or biomolecules to human trials following animal or non-animal testing. Nonprofits and other advocacy groups feel that the FDA should rely more on computer modeling, organ-on-a-chip, and other non-animal approaches developed in the last 10 to 15 years for conducting human drug studies.

The FDA typically requires toxicity testing on one rodent (such as a mouse or rat) and one non-rodent (such as a monkey or dog). The biopharmaceutical companies involved conduct such tests using tens of thousands of animals each year. However, more than 90% of drugs that enter human clinical trials fail because they are unsafe or ineffective.

"All possible novel drugs must be investigated for safety in animals before initiating human clinical trials," Pfizer stated. According to the Biomedical Research Foundation, animals typically utilized in pharmaceutical studies include cats, dogs, pigs, monkeys, guinea pigs, hamsters, mice, rats, and rabbits.

As with cosmetic animal testing, laboratory workers may suffer emotional effects and even post-traumatic stress disorder from having to inflict so much pain on innocent animals. The NIH reports that approximately 95% of all drugs considered safe in animal testing fail in human clinical trials, proving that animal testing is ineffective.

Organoids are three-dimensional cell assemblages that incorporate many cell types and display at least some of the physiological properties of the organ to which the cells belong. Because stem cells have the ability to differentiate into all cell types, stem cell technology provides the foundation for creating organoid systems. Organoid technology has enormous promise for research in areas like developmental biology, disease pathology, cell biology, regenerative mechanisms, precision medicine, and drug toxicity and efficacy testing. Organoid culture provides a very informative supplement to conventional 2D culture methods and animal model systems for these and other applications.

"Animal models are frequently more incorrect than right," says Harvard bioengineer Don Ingber. Emulate, a human organ chip developer based in the United States, is currently commercializing the organ chip technology created in his lab.

Such organ chips are often made up of hollow channels embedded in a silicon-based polymer that is about the size of a USB flash drive, with living cells and tissues from organs such as the brain, liver, lungs, and kidneys placed within. Fluid runs through them to replicate blood flow through microvessels, and fluid flows through tissue as it would in a living organ.

Drug damage often presents itself in the liver, which breaks down drugs for elimination. A toxicity alert is issued when an investigational drug goes through the human liver chip and harms cells. According to Emulate's study, its liver chip properly detected 87% of all sorts of drugs that either failed in clinical trials due to liver toxicity or were discontinued or pulled back from the market due to liver toxicity. Furthermore, no non-toxic drugs were mislabeled by the chip.

It is unclear how much the new law will change the game at the FDA. Although the Act permits the FDA to approve a drug for human clinical trials without using animals, it does not mandate it.