The path from initial lab work on a drug to final approval is a long, labor-intensive process, according to the Food & Drug Administration. Generally, 10 to 15 years elapse between the initial stages of laboratory research on a pharmaceutical and its introduction into the marketplace.

Before a drug company or research institution can submit an Investigational New Drug Application (INDA) to the Food & Drug Administration, it does an average of six-and-a-half years of basic discovery work and preclinical testing in lab animals.

The INDA includes the results of the discovery work and testing in lab animals and describes the human testing that the sponsor--a company or research institution--proposes to do. At this stage, FDA decides whether it would be reasonably safe to test the drug on humans.

Clinical trials cannot begin until the trial protocols are reviewed by a local institutional review board consisting of a panel of scientists and nonscientists from hospitals and research institutions. These protocols describe the type of people who will participate in the trial, the schedule of tests and procedures, the drug and dosages to be used, and the length and goals of the study. The board also makes sure the participants have given consent and are informed of potential risks, and that researchers will take steps to protect patients from harm.

In the first phase of clinical trials--called Phase I toxicity testing--the drug is administered to 20 to 80 healthy volunteers for about a year and a half. At this point, researchers are looking at safety and trying to determine probable safe dosages. They are also attempting to detect the most frequent side effects and to learn how the drug is metabolized and excreted.

If the results of Phase I trials indicate acceptable toxicity, Phase II studies begin. Generally, out of five drugs tested in Phase I trials, only two emerge as acceptable and progress to Phase II. In this stage, the drug is given to 100 to 500 volunteer patients to determine effectiveness. This phase takes about two years, and only about half the drugs tested in Phase II emerge as successful.

If evidence of effectiveness is shown in Phase II, the drug is then given to 1,000 to 5,000 volunteer patients in Phase III, which lasts about three-and-a-half years. Most drugs that are successful in Phase II also are found acceptable in Phase III.

After the first three phases of clinical trials are completed, over a total of about seven years, the drug sponsor submits a New Drug Application (NDA) to FDA. The application includes all animal and human data, analyses of the data, information on how the drug acts in the body, and information on how it is manufactured. The agency acts on 90% of NDAs within 10 months. On average, only one in five drugs that enter clinical testing is eventually approved by FDA.

There is fairly continuous interaction between FDA and the drug sponsor throughout the review process. For example, before final approval of the asthma drug Singulair, FDA and Merck Research Laboratories had six meetings and 28 teleconferences.

The FDA review team consists of medical doctors, chemists, microbiologists, pharmacologists, and statisticians. If they judge a drug to be safe, this means they have decided that its benefits outweigh its risks, which are generally manifested as side effects. All drugs have side effects.

Sometimes, advisory committees of outside experts help FDA decide on NDAs. Their advice is usually, but not always, followed.

After FDA approves a drug and marketing begins, Phase IV studies may commence. These may explore new uses for the drug, new patient populations, and the long-term effects of the drug.

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