Breakthrough: FDA no longer requires drug animal testing, presenting an opportunity for organoids

Recently, the journal Science published an article stating that the FDA will no longer require animal testing before clinical trials of drugs.

On September 29, 2022, the United States Senate unanimously passed the FDA Modernization Act 2.0, aimed at significantly reducing the use of animal testing in the coming years by eliminating federal mandates for animal testing on new and generic drugs.

In December, the U.S. House of Representatives approved the bill as part of the Consolidated Appropriations Act, signed into law by President Biden.

This change has been welcomed by animal welfare organizations and may signal a significant shift in drug safety regulation after more than 80 years of reliance on animal testing.

Tamara Drake, Director of Research and Regulatory Policy at the non-profit animal welfare organization Humane Economy Center, said: "This change is huge and it's a victory for the industry. It's also a victory for patients who need treatment."

In 1938, President Roosevelt signed the Federal Food, Drug, and Cosmetic Act, requiring evidence of safety for all drugs before they could be marketed and allowing drugs or biologics to be promoted to human testing after animal or non-animal testing.

But for the changes today, some people are in favor of them:

In actual practice, the FDA usually requires toxicity testing on one type of rodent (such as mice or rats) and one type of non-rodent animal (such as monkeys or dogs) in order to approve drugs.

Every year, various pharmaceutical companies use tens of thousands of animals for toxicity testing. However, 9 out of 10 drugs fail due to safety or effectiveness issues after entering clinical trials, so some people believe that animal experiments are a waste of time, money, and lives, with a well-known example being the thalidomide-induced phocomelia in 1960.

In 2019, Vanda Pharmaceuticals also sued the FDA, accusing it of being unreasonable to require additional toxicity testing on a nausea drug on dogs. In 2020, a US judge ruled against the company, citing the animal testing requirements in the law at the time that governed FDA drug evaluation.

Tamara Drake believes that when approving drugs for human trials, the FDA should rely more on computer modeling, "organ chips," and other non-animal methods developed in the past 10 to 15 years.

This has also given rise to new technologies, such as organoids.

The journal Science provided an example in the article, citing the development of organ-on-a-chip technology by Don Ingber, a board member of Emulate and a bioengineer at Harvard University.

These chips typically consist of hollow channels embedded in silicon-based polymers, roughly the size of a computer thumb drive. The channels contain live cells and tissues from organs such as the brain, liver, lungs, and kidneys. Fluid flows through them to simulate blood flow in tiny vessels and to track fluid movements within tissues, just as it would in living organs. In the human body, drug damage often manifests in the liver because it breaks down drugs for elimination. When experimental drugs pumped through the liver cause cellular damage, human liver chips can detect this toxicity.

According to a study published by Emulate, the liver chip correctly identified 87% of toxic drugs, including those that failed clinical trials due to liver toxicity and drugs that were withdrawn from the market due to liver damage.

However, some people believe that implementing this bill may be difficult.

The Communications Director of Americans for Medical Progress believes that non-animal technology is still "in its infancy" and cannot replace animal models for many years to come. He pointed out that the FDA still has significant discretion to require animal testing, and he does not expect the agency to change its position quickly.

Wendy Jarrett, CEO of Understanding Animal Research in the UK, said that non-animal methods cannot determine all the risks that a drug may pose to human test participants. We can put a new candidate drug on a bunch of liver cells. We can see that it will not harm them, but what we don't know is whether it will make people cough or damage their intestines or brain.

Many people believe that although animal testing has always been a controversial topic in scientific ethics, there is currently no better alternative solution and the implementation of this new law may be slow.

The chief scientist of the FDA also stated that the agency supports scientifically-based alternative methods and provides necessary data to demonstrate the safety and efficacy of products, and that they will attempt to move away from animal testing when other methods are ready. In addition, the agency applied for and received $5 million in funding in 2013 to launch a program aimed at developing alternative methods to reduce, refine, and replace animal testing.

However, toxicologists at the FDA still prefer animal testing because it allows for examination of the potential toxicity of drugs on each organ after the animals have been euthanized.

In summary, attitudes towards the new law are still divided, and its main role may not be for all pharmaceutical companies to immediately abandon animal testing, but rather to pave the way for serious discussions about non-animal testing at the FDA and in the pharmaceutical industry. At the same time, this provides confidence to companies that are developing non-animal technologies, promoting the rapid development of computer modeling, 3D organ cultivation, organ chips, and other technologies.

In particular, in the race for organ chips, last August, the world's first drug based entirely on "organ chip" research obtained preclinical data and was approved by the FDA for clinical trials (NCT04658472), marking a milestone in progress.)

Reprinted from NetEase News