How the FDA can cut back on animal testing


As an appointed senior executive in the Trump administration’s Food and Drug Administration, I have seen some officials put policy above scientific advances in animal testing. If the FDA prioritizes science, health, and ethics over political considerations, it should support the development of in vitro and computational approaches to reduce animal testing.

The old rules govern the FDA’s current approach to this. In 1962, Congress passed the Kefauver-Harris (KHA) Amendments to the Federal Food, Drug and Cosmetic Act. Among other requirements to “modernize” scientific methodologies, this now dusty law has authorized the FDA to impose animal testing requirements for the approval of new drugs. In addition, Sec. Section 312.20 of the Code of Federal Regulations describes the requirements for investigative new drug submissions (INDs), and the FDA also requires comprehensive animal studies for the approval of new drugs in humans. Last year, in credits, the FDA was tasked with updating its regulations to allow for non-animal methodologies. The agency was due to report on its progress by September 30, but it missed that deadline.

The existing regulations are extremely precise. Drug manufacturers are advised to use animal testing to discern pharmacology (how a drug exerts its effects) and toxicology (the dose at which it causes unwanted effects), as well as radiation absorption and effects on the reproduction. The regulations do not allow any flexibility to explore or implement new methods that may be more predictive for humans. Only the FDA has the power to initiate any change. Companies must follow these regulatory rules to get an investigational drug through the review process and eventually gain FDA approval.

Beyond regulation, other FDA guidance documents list and prioritize animal testing. Guidance documents are meant to be non-binding recommendations that reflect the agency’s thinking on a topic, but do not carry the weight of regulations – or are they? Recently, Vanda Pharmaceuticals tried to avoid conducting a nine-month dog study, saying the study, which would kill dozens of beagles, had no scientific justification. But FDA reviewers would not budge, referring to their own guidance documents.

The number of animal tests required each year is staggering. In the United States, more than 110 million mice and rats are killed each year in the name of science, as are other animals, including monkeys, rabbits, pigs, guinea pigs, cats, and dogs.

And the benefits are not always obvious. When the KHA was adopted, it was the scientific standard of its time. Sixty years later, scientists have learned that animal test results are not necessarily useful or predictive in humans. About 90% of early phase clinical trials fail after extensive animal testing has already been conducted. Despite this, the FDA requires that animal testing be performed for almost all INDs it reviews, regardless of their usefulness.

Animal testing is often unnecessary. Aside from the many species and breeds of animals involved, the variety of metabolic pathways and drug metabolites in animals results in variation in efficacy, toxicity, disease latency, and dosage regimens. Often the results are only vaguely relevant to humans. For example: Isotretinoin, also known as Accutane, causes birth defects in rabbits, monkeys and humans, but not in mice or rats. Corticosteroids are known to cause birth defects in many animal species, but not in humans. Thalidomide is not teratogenic (affecting the development of an embryo or a fetus) in animals but is in humans. Many of the studies required by the FDA are nonsense, including eye and skin irritation testing of drugs approved only for oral administration. The National Institutes of Health recognize that “about 30 percent of promising drugs have failed in human clinical trials because they have been shown to be toxic despite promising preclinical studies in animal models.”

All of this can lead to excruciating results. It was recently reported that the National Institute of Allergy and Infectious Diseases awarded $ 424,455 in public funds for a study that locked beagles alone in cages in the desert for nine days to attract parasite-infested sandflies, then starved those sandflies, then let them feed on live and restrained beagle heads. The beagles are said to have “vocalized in pain” although they were heavily sedated during the experiment.

As a research scientist in experimental medicine at Pfizer in the early 2000s, I was responsible for overseeing “LD50” testing in animals. My colleagues and I needed to determine the lethal dose – the amount that would kill 50 percent of the animals after a single dose. Often times this meant force-feeding dogs and rodents with several grams of experimental drugs before the first human trials (FIHs) that dose humans with just a few milligrams of the drug, a tiny fraction of the dose we administered. To animals. We then went up logarithmically until we found the maximum tolerated dose. This was done to meet the mandates of the FDA.

Major advances have been made in drug testing since the regulations in force were drafted. These include non-animal preclinical methodologies. Consider “Organ-on-a-Chip” (OOC) technology. As a former White House-appointed senior official to the FDA, I was tasked with advising the Commissioner of the FDA and the White House on ways to modernize and accelerate drug development. One of my proposals was to advance OOC technologies, which potentially did both. OOCs are made by programming or culturing human cells obtained from relevant human organs (heart, liver, kidney, brain, gastrointestinal) in a microenvironment “chip”, where micro-doses of experimental drugs can be. applied. The OOCs can then be linked to form model human systems, adding additional complexity. Since human cells are used to populate these OOCs, this in vitro the technology bypasses – and could one day dramatically reduce – the cruelty and experimental limitations inherent in animal testing.

The ethical and technological advantages of such innovations are obvious. OOCs have the potential to predict safe doses more clearly and quickly than animal testing. Alternatives to animal testing are already enjoying bipartite support. And such innovations have public health benefits and efficiency.

Unfortunately, some FDA officials are reluctant to change. While there, I spent months preparing a detailed proposal in which funding would be provided to a few pharmaceutical companies to implement OOCs in tandem with existing animal testing. The aim was to test the hypothesis, supported by some comparative studies, that OOCs could accelerate preclinical drug development by more accurately predicting safety and efficacy in humans. To my amazement, I have been blocked every step of the way by career management bureaucrats at the FDA. One of them, Patrizia Cavazzoni, had a reputation for refusing to work with Donald Trump’s political figures; she was promoted by President Biden shortly after her inauguration. Cavazzoni and his team wouldn’t even consider listening to my research or scientific recommendations.

Americans overwhelmingly frown on animal testing and would likely rally to put the brakes on it, especially if they knew about technologically superior alternatives like OOC. Over the past seven decades, technology has advanced dramatically, as has our view of the role of animals in society. To keep up with the latest technology, the FDA should strive to reduce its reliance on animal testing by embracing – without ignoring – innovative alternatives.

Photo by Anna Moneymaker / Getty Images

About Sally Dominguez

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