Before regulators approve a drug, it typically has been tested on hundreds of animals. The FDA requires initial testing in at least two species: one rodent, one nonrodent. By the end of the process, mice, pigs, rabbits, dogs, monkeys and other animals may have been used (Wall Street Journal, March 30, 2007).
Drug testing in animals began with the Diethylene glycol tragedy in 1937 when many people died after taking sulfa drugs to which it had been added. When it was fed to animals it was found that they too were sensitive to the chemical. And animal testing was born.
Today animals are used primarily in ADMET tests which stands for:
A – How the drug is absorbed in the body
D – How it is distributed to the tissue
M – How the body metabolizes it
E – How the body eliminates it
T – The toxic effects
The existing approaches to safety testing in the preclinical phases of drug development are not reliable enough to identify potential toxic liabilities for humans. In addition, regulatory agencies and the pharmaceutical industry understand that the present "gold standard" of animal testing is not the answer, as rodent testing is about 50 percent predictive of human toxicology.
It can happen that a product doesn't hurt animals, but turns out to be poisonous to patients. This occurred with the catastrophic British trial of an experimental biotech drug called TGN1412, meant to treat leukemia and other diseases. It didn't cause problems when tested in numerous animal species, including rabbits and monkeys. Then six people took it in a small initial study and had life-threatening convulsions and organ failure. All six men were hospitalized in critical condition approximately one hour after being given the drug. British regulators blamed an "unpredicted biological action of the drug in humans" that wasn't foretold by the "apparently adequate" preclinical studies.
A study begun in 1976 by the FDA to follow all the new medications it had released over a ten year period, found that 102 of the 198 new medications (52%) were either recalled or relabeled, due to side effects not predicted in animal tests.
Another study examined six drugs which were already known to cause certain side effects in humans. The study determined that animals correctly predicted 22 side effects, but incorrectly identified 48 side effects that did not occur in humans, and missed 20 side effects that did occur in humans. This means that the animal models were incorrect 68 out of 90 times (76% of the time).
The medical decision to prescribe hormone replacement therapy (HRT) to post-menopausal women did not work out as predicted by the animal models. Women who received HRT suffered more strokes and heart attacks that those who did not take HRT.
It’s all too familiar. Researchers announce the discovery of a new drug that minimizes the symptoms of disease in animals. Then, a few years (and often many lost lives) later, the drug fails under a cascade of media derision and widespread litigation. The reality is that people do not need drugs that are found to be safe in animals, or even in most humans – people want what is safe and effective for them.