U.S. Food and Drug Administration (FDA)
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| The FDA requires extensive toxicity testing on animals. |
Drugs
The marketing of drugs and other pharmaceutical products in the U.S. is controlled under the federal Food, Drug and Cosmetics Act, which empowers the FDA's Center for Drug Evaluation and Research to require extensive toxicity testing on animals before a new drug is deemed "safe" for marketing. In order to satisfy FDA data requirements, thousands of rats, mice, rabbits, dogs, and primates are killed in "pre-clinical" laboratory poisoning experiments to test the safety of new drugs (including all ingredients and even minor differences in formulation). Commonly required animal tests include the following:
- Acute (short-term) toxicity: 7 to 20 rats + dogs or primates
- Subchronic (14- to 180-days) toxicity: rats + dogs or primates
- Chronic (lifetime) toxicity: 120 rats + 32 dogs or primates
- Cancer-causing effects: 400 rats + 400 mice
- Toxicity to reproductive systems
- Segment I (reproductive toxicity in 2 generations): 2,500 rats
- Segment II (birth defects): 900 rabbits + 1,300 rats
- Segment III (peri- and postnatal effects): rats
- Absorption, distribution, metabolism, excretion, and pharmacological interactions of active ingredients
- Specialty studies
- Genetic toxicity: 80 hamsters/mice x 2 to 5 separate studies
- Immune system toxicity: 32 rats
- Skin/eye/mucosal irritation: 3 rabbits per test
In fact, the FDA recently reported that 92 out of every 100 drugs that successfully pass animal trials and go into human clinical testing proceed to fail during the human clinical trial phase. The world was astounded in February 2006, when six men participating in phase I testing of a new therapeutic antibody fell into comas and almost died; these antibodies had been tested on primates without a hint of such problems.
The problem is that species differences are so large that animal results are, at best, a very rough approximation of what will happen in humans or, at worst, dangerously misleading. The alternative is to advance science to the point where preclinical tests are based on human biology, which will better predict what will happen in the clinic to real human volunteers or patients. As of today, cutting-edge technologies such as the Hurel biochip, which features microfluidic circuits lined with cells from various human organs, allow us to better predict complex human reactions.
Biologicals
"Biologicals" are medicinal products, such as vaccines, hormones, antibodies, and blood products, which are derived from a living organism. In the U.S., biologicals are regulated by the FDA's Center for Biologics Evaluation and Research. Because of their origin, biologicals must undergo extensive quality control during production. Vaccine testing in particular consumes an estimated 10 percent of all "biomedical" animal use every year (an estimated 10 million animals) because they are often produced by weakening, inactivating, or detoxifying a virulent microorganism or toxin. Each batch of the finished product is tested on animals, causing them pain, suffering, and death.
Safety testing is carried out to try to determine that people who are inoculated with the vaccine are not infected by the pathogen. A common study is the "abnormal toxicity test," in which guinea pigs and mice are injected with a biological product and observed for one week. The test may be repeated multiple times for the same product, until all of the following criteria are met:
- All of the animals survive the observation period.
- None of the animals shows any weight loss at the end of the observation period.
- None of the animals shows toxic signs.
"Potency testing" is carried out to determine the effectiveness of inactivated (nonliving) vaccines in protecting the recipient against bacterial or viral infections. These studies use "challenge" tests, in which large numbers of animals, which are usually mice, rats, guinea pigs, rabbits, and/or chickens, are inoculated with a vaccine and then "challenged" through purposeful infection with the disease that the vaccine is designed to protect against. For example, the potency of the whole-cell pertussis vaccine is measured using the "Kendrick test," in which the pertussis toxin is injected directly into animals' brains, after which the animals are monitored to see how many die.
An almost identical procedure is used to test the potency of rabies vaccines, using the "NIH test." In this test, 160 mice per batch are used; some are given the protective vaccine but some are not. All the mice then receive injections of live rabies virus in their brains through their skulls. This is both extremely painful and completely irrelevant to normal routes of infection. Approximately half of the animals develop and/or die of rabies, a painful neurological disease involving tremors, loss of control over one's body, and severe weight loss. The real shame is that a completely non-animal method of testing the potency of rabies vaccine has existed for more than 30 years, but government regulators have yet to officially accept it.
The potency of tetanus and diphtheria vaccines is determined by immunizing guinea pigs or rabbits with the pathogen in question, collecting their blood (usually by bleeding them to death), and then measuring the antitoxin titer using a "toxin neutralization test." In this test, the aim is to determine the dilution of a toxin mixture that causes death and/or clinical signs of disease in half the mice within five days of their being injected. Although it is unknown how many animals are subjected to this procedure in the U.S., it is estimated that as many as 10,000 mice are killed in this test in the Netherlands alone every year.
The relevance and appropriateness of continued batch safety testing has been called into question, not only because of the inherent cruelty in the animal tests used, but also because the use of increasingly automated manufacturing processes has markedly decreased the variability between batches. While this will not necessarily eliminate animal testing altogether, it has the potential to greatly reduce the number of animals who are killed in safety testing.
Medical Devices
The FDA's Center for Devices and Radiological Health is responsible for the licensing of medical devices, which include an extremely broad range of products, such as cardiac pacemakers, stents, insulin pumps, and surgical devices. A great deal of animal testing for these products relates to the safety of the materials in the medical devices: the plastic polymers, the metals, and the ceramics. These materials are implanted into an animal's tissues, or else chemicals leached from these products are injected into their tissues to observe the toxicity to animals. Researchers are generally looking for toxicity to cells and allergic potential, as well as the acute and chronic toxicity tests described above (under Drugs). Similar to biologics, each batch of a medical device is also tested for quality control, using animals.
Testing the effectiveness of medical devices is often difficult because they are specific to human anatomy and physiology. For this reason, pigs, sheep, and dogs are the most commonly used species since they have the misfortune of being relatively similar to humans in overall size and in organ size. Even so, the geometry of the animals' bodies is often too dissimilar to be of use.
Alternatives include benchtop simulators of various human organs and computer programs that can simulate, for example, the effect of a particular heart rhythm as encoded into a pacemaker.
What You Can Do
1) Write to the FDA commissioner and ask that the FDA make it mandatory to use non-animal methods whenever they exist, instead of animal tests:
Dr. Margaret A. Hamburg
Acting Commissioner
Food and Drug Administration
5600 Fishers Ln.
Rockville, MD 20857
301-796-5000
margaret.hamburg@fda.hhs.gov
2) Write to the FDA's Center for Biologics and demand that it validate the non-animal potency test for rabies vaccine and require that vaccine manufacturers use this superior method:
Lorrie McNeill, Director
Division of Communication and Consumer Affairs
Center for Biologics Evaluation and Research
Food and Drug Administration
11400 Rockville Pike
Rockville, MD 20857
301-827-2000
301-827-3843 (fax)
lorrie.mcneill@fda.hhs.gov
