Congress Must Rehaul Animal Testing Paradigm for New Drug Development
FDA Modernization Act Can Deliver Game-Changing Results for Patients and for Animals
Since 1938, the Federal Food, Drug and Cosmetics Act (FFDCA) has required animal testing for new drugs. In every and all cases. Hard stop.
The Food and Drug Administration (FDA) religiously requires the use of animals in testing even when its own scientists and pharmaceutical industry scientists believe that non-animal testing methods are superior for measuring the safety and effectiveness of new drugs. FDA says the law is unambiguous in its mandate.
Here’s a policy area where the stakes couldn’t be higher. If people don’t get palliative treatments, they may experience unremitting pain or discomfort. If they cannot access a cure, their lifespan is shortened.
Call the government’s response what you will. Bureaucratic. Even robotic. Tone deaf. Deadly.
You would think that government personnel would demand Congress act to change the statute to unlock a storehouse of new testing methods. But no, FDA has been silent in calling on Congress to change the legal requirement that guides its drug approval authority.
FDA Modernization Act Aims to Speed Testing, Spare Animals
A group of House lawmakers are aiming to turn over tables at FDA. U.S. Representatives Vern Buchanan, R-Fla., Elaine Luria, D-Virg. Nancy Mace, R-S.C., Mikie Sherrill, D-N.J., and Brendan Boyle, D-Pa. introduced the FDA Modernization Act, H.R. 2565, to allow scientists to use the best testing methods to develop drugs to treat cancer, Alzheimer’s and other scourges in our society. With so many lives at stake – animals on the front end of the process and human patients at the back end – why opt for inferior testing methods?
The COVID-19 pandemic is a reminder that we, as complex biological organisms, are vulnerable and that we need vaccines and other drugs to ward off disease. The pandemic has shined a spotlight on our entire drug approval process and revealed how much is at stake. AIDS was, for two decades, a death sentence; now drugs allow HIV patients to live long, productive lives. In other cases, cures and palliatives have been maddeningly difficult to develop. Heart failure and cancer remain the two biggest killers of Americans.
Despite billions in funding for animal research into Alzheimer’s disease and cancer over several decades, the failure rate in drug development remains 97% for cancer and 99% for Alzheimer’s. In addition to being ineffective, many drugs are unsafe. Just listen to the litany of health warnings in the narration for television advertisements for new drugs. It’s not surprising then that adverse reactions to drugs, taken as prescribed, constitute the fourth leading cause of death in the United States.
Study costs can be astronomical and the time frame often extraordinarily slow. Whether it’s a heart medication or a cancer drug or an arthritis treatment, data show that it typically takes 10 years and an investment of $2 – $12 billion for a new drug, slowing delivery of palliatives and cures for patient groups, driving up drug costs, and sacrificing countless animals, including mice, rats, dogs, and non-human primates.
Draize Tests Demonstrates Problems with Existing Paradigm
One of the best-known and most inhumane and unnecessary forms of animal use in science is the acute toxicity measure known as the Draize test, devised in 1944 to measure irritancy caused by cosmetics, but subsequently becoming the most common method for assessing skin and eye irritancy in pharmaceuticals. The Draize test calls for solutions to be applied directly into the animals’ eyes, causing intense burning, itching and pain. Clips are placed on the rabbits’ eyelids to hold them open during the test period, which can last several days, during which time the rabbits are placed in restraining stocks. The chemicals often leave the eyes ulcerated and bleeding. In the Draize test for skin irritancy, the test substances are applied to skin that is shaved and abraded (several layers of skin are removed with sticky tape), then covered with plastic sheeting.
The Draize has remained the traditional test for nearly eight decades, despite scientific studies for the last 40 years showing deficiencies with Draize in predicting human response and perfectly suitable human-relevant, non-animal test methods.
Since 2005, FDA has informally stated that Draize test data are not required for primary skin and eye irritation testing, but that statement is functionally irrelevant given the FFDCA requirements. The law requires animal testing and the application of potentially toxic substances and the clipping open of the eyes of the animals continues unabated.
A 2015 study reveals that the Draize test was used in 94 percent of all skin irritation and 60 percent of all eye irritation tests for all new drugs approved by FDA between the years 2011- 2014. Of the drugs for which the Draize test was conducted, 76% were for systemic, not topical, administration, thus no irritancy testing of any type was even necessary to begin with.
While the rabbits can’t close their eyes, government leaders seems to keep their eyes shut to necessary changes in the law. There are better methods available, and everybody in the field knows it, but the mistreatment of animals and the use of inferior testing methods continues because we are in a statutory straitjacket.
The FDA Modernization Act, however, would make clear to sponsors that they can bypass torturing rabbits and other animals and use human-relevant test methods such as reconstructed human epidermis (RhE) for skin irritation, which is acknowledged to be more accurate in predicting effects on humans than the Draize test.
“The most predictive technologies in existence should be available to drug sponsors to provide the safest and most effective medicines for patients,” said Gary K. Michelson, M.D., Founder and Co-chair, Michelson Center for Public Policy. “Animal data shouldn’t be the automatic reflex if there are superior non-animal test methods that predict what will happen in human clinical trials.”
Animal Tests Not Predictive of Human Drug Response
Just how unreliable are these mandatory animal tests? In 19 of 20 cases, when a new drug passes muster in animal tests – whether it’s rabbits, mice, dogs, or primates – it fails in human clinical trials. Think of all the time, intellectual energy, and animal lives wasted because the government requires an archaic process for safety and efficacy testing.
And we’ve known this for a long time. Vioxx appeared safe and even beneficial to the heart in animal tests, but was withdrawn from the global market in 2004 after causing an estimated 320,000 heart attacks, strokes and cases of heart failure worldwide – 140,000 of them fatal. Nine of 11 studies on mice and rats had shown Vioxx or other COX-2 inhibitors to be safe for animal hearts and blood vessels. In fact, six different animal studies—in four different species—showed Vioxx was actually protective against heart attacks and vascular disease.
The FDA is not unleashing the power of scientific innovation to attack disease in America, even as these alternative methods gain traction in other regulatory settings. According to one study, cell-based assays are predicted to grow at a compound annual growth rate (CAGR) of 10.2%, and organ-on-a-chip assays should grow at a compound annual growth rate (CAGR) of 39.9%.
Updates to the FFDCA would provide drug sponsors with options for testing the safety and efficacy of drugs that would improve clinical trial attrition rates, cut time to market in half for new drugs, and substantially reduce research and development costs as much as fivefold.
“I want to see research move away from the animal model, not only for the animals but for the American people who are in need of faster delivery of cures for devastating diseases with drugs at a lower price point,” says Rep. Buchanan. “That means that research must focus on human biology, not animal biology. Our bill does just that.”