FDA Announces Plan to Phase Out Animal Testing. Will That Work?
Human organs-on-chips and organoids offer new alternatives to animals for drug development, but there is still a long way to go. With the FDA’s goal of replacing animal testing, scientists look to organoids and organ-on-a-chip technologies as replacement alternatives.
In April of this year, the Food and Drug Administration (FDA) announced a new roadmap that aims to replace animal testing in the development of new drugs with more human-relevant methods. The goal is to improve drug safety, accelerate the evaluation process, shorten drug development timelines, reduce costs, and spare animal lives. The FDA aims to make animal testing the exception rather than the norm within three to five years. Is this possible?
The FDA has required animal testing of new drugs since the 1930s after more than 125 American adults and children died after ingesting an antibiotic elixir that mistakenly contained the poison found in antifreeze—diethylene glycol—which was then thought to be just a sweetening agent. Animal testing remains the mainstay of drug evaluations by the FDA, and it undoubtedly has helped prevent other potentially dangerous chemicals from reaching patients. However, on the flip side, the results of drug tests in animals fail to predict future responses in humans more than 90 percent of the time.1 It is also likely that many drugs that could have been safe and effective in humans never received approval because they were found to be toxic in early animal studies. Aspirin is a great example; we are all lucky because it was first marketed before 1900.
The scientific and ethical limitations of animal testing have received progressively more attention over the past twenty years. Finally, in December 2022, Congress passed the FDA Modernization Act 2.0 which authorized the agency to use data generated with advanced human cell-based assays and computer models as alternatives to animal testing when considering the safety and effectiveness of a drug. But since that time, Congress has seen little evidence that the FDA is walking the walk along this path. As a result, it has been considering passage of the FDA Modernization Act 3.0 that compels the agency to take more active steps to phase out animal studies. This is precisely what the new administration chose to do on its own in April.
Artificial Intelligence Could Help Replace Animal Models…But Not Right Away
While the FDA’s new accelerated timeline for replacing animal testing is aspirational, they believe that recent advances in artificial intelligence (AI)-based computational models and in new advanced human cell culture models, namely organoid and organ-on-a-chip (organ chip) technologies could now make this a possibility. While AI could potentially dive through heaps of data to pull out drug candidates that are safe and effective in humans in the future, the field is still in its infancy. More importantly, AI models are only as good as the data they ingest, and predictions made based purely on existing data from the web and past publications are essentially computer-based correlations or "guilt-by-association." The true power of this approach will be tested when AI predictions can be tested in human-relevant experimental assays, with the data being fed back into the model to refine and optimize predictions through iteration. At present, drugs being developed with AI models still require validation through testing in animals, and now potentially in human organoid or organ chip models.
Human Organoids and Organ Chips as Alternatives to Animal Testing
The FDA's proposal to explore human organoid and organ chip technologies, along with AI, is timely and wise because these different approaches can synergize to produce results that are highly predictive of human drug responses. Organoids are small balls of stem cells isolated from human patients that reform specialized tissue structures and functions, such as finger-like intestinal villi, when grown within a Jello-like matrix and bathed in a nutrient medium. Because these organoid cultures express the molecular machinery of human cells rather than rat or dog cells, they are much more relevant testbeds for both mechanistic studies and for testing drugs that are designed to go into humans. But the same human cells that grow within these organoids behave differently when they are naturally nestled close to connective tissue containing blood vessels, contact immune cells, and experience physical forces associated with blood flow, breathing motions, and body movements as they do within living organs inside our bodies.
