The drug research process is complicated, time-consuming, and costly; and the end result is never known at the outset. Literally hundreds, and sometimes thousands, of chemical compounds must be made and tested to find one that can achieve the desirable result without too serious side effects.
Such a complicated process costs vast amounts of time and money. The FDA estimates that, on average, it takes eight-and-a-half years to study and test a new drug before the agency can approve it for the general public. That includes early laboratory and animal testing, as well as later clinical trials using human subjects.
The role of the FDA in the early stages of drug research is small. The Federal Food, Drug, and Cosmetic Act does not give the agency responsibility to develop new drugs. So, FDA physicians, scientists, and other staff review test results submitted by drug developers. The FDA determines whether the drug is safe enough to test in humans and, if so--after all human testing is completed--decides whether the drug can be sold to the public and what its label should say about directions for use, side effects, warnings, and the like.
Building on Good Science
New drug research starts by studying how the body functions, both normally and abnormally, at its most basic levels. The pertinent question is, "If the body's functioning is changed, will I have a useful drug?" That, in turn, leads to a concept of how a drug might be used to prevent, cure, or treat a disease or medical condition. Once the concept has been developed, the researcher has a target.
Sometimes, scientists find the right compound quickly. More often, hundreds or even thousands must be tested. In a series of test-tube experiments called assays, compounds are added one at a time to enzymes, cell cultures, or cellular substances grown in a laboratory. The goal is to find which additions show some chemical effect. Some may not work well, but may hint at ways of changing the compound's chemical structure to improve its performance. The latter process alone may require testing dozens or hundreds of compounds.
A more hightech approach is to use computers to simulate an enzyme or other drug target and to design chemical structures that might work against it. A computer can show scientists what the receptor site looks like and how one might tailor a compound to block an enzyme from attaching there. However, while computers give chemists clues to which compounds to make, they don't give any final answers. Compounds made based on a computer simulation still have to be put into a biological system to see whether they work.
A third approach involves testing compounds made naturally by microscopic organisms. Candidates include fungi, viruses, and molds, such as those that led to penicillin and other antibiotics. Scientists grow the microorganisms in what they call a fermentation broth, one type of organism per broth. Sometimes, 100,000 or more broths are tested to see whether any compound made by a microorganism has a desirable effect.
To this point, the search for a new drug has been confined to a laboratory test tube. Next, scientists have to test those compounds that have shown at least some desired effects in living animals. In animal testing, drug companies make every effort to use as few animals as possible and to ensure their humane and proper care. Two or more species are typically tested because a drug may affect one differently from another. Such tests show whether a potential drug has toxic side effects and what its safety is at different doses. The results point the way for human testing and, much later, product labeling.
So far, research has aimed at discovering what a drug does to the body. Now, it must also find out what the body does to the drug. So, in animal testing, scientists measure how much of a drug is absorbed into the blood, how it is broken down chemically in the body, the toxicity of its breakdown products (metabolites), and how quickly the drug and its metabolites are excreted from the body. Sometimes, such tests find a metabolite that is more effective than the drug originally picked for development.
The Wrong Road
More often than many scientists care to admit, researchers just have to give up when a drug is poorly absorbed, is unsafe, or simply doesn't work. The organization Pharmaceutical Research and Manufacturers of America estimates that only 5 in 5,000 compounds that enter preclinical testing make it to human testing, and only 1 of those 5 may be safe and effective enough to reach pharmacy shelves. Nevertheless, progress may yet be made. Occasionally, a stubborn scientist keeps looking and finds a usable compound after others had given up. In other cases, compounds may be put aside because they failed to work on one disease, only to be taken off the shelf years later and found to work on another.