In 1906, the Pure Food & Drug Act established authority for a regulatory agency that eventually became the FDA. Today, the FDA alone decides whether and how pharmaceutical companies may test drugs in Americans and, ultimately, whether the companies will be allowed to sell a drug. Here's an overview of the FDA drug approval process.
What occurs between the first news report about a promising drug and the prescription in your hand is a lengthy process that involves a structured series of studies. If all goes well, the testing process leads to FDA approval: the legal right to sell the drug in the United States.
When a newspaper article ends with the statement "further testing is required," that's a reference to the three phases of clinical testing that occur between the laboratory tests in animals and FDA approval.
FDA Approval: Phase I -- The first clinical studies involve a relatively small number of patients or healthy volunteers, usually 20–80 individuals. In Phase I studies, researchers determine the biological effects of the drug in the human body at various doses -- including any harmful side effects -- and measure how well the drug is absorbed, how it is metabolized, and how long it stays in the body before it is eliminated. A candidate drug could be rejected in this phase for a number of reasons. The drug may turn out to be too toxic or the body simply may not absorb it well enough. Many drugs that look promising in mice and in test tubes fail to pass muster during Phase I clinical trials.
FDA Approval: Phase II -- If the Phase I trials are favorable, the next step is to test the drug in a larger number of subjects, typically around 100–300 individuals. Again, researchers look at safety, but now they also try to establish whether the drug provides a benefit in treating people with a specified disease or condition. Pharmacologists refer to this as a drug's "indication." For example, the FDA-approved indication for cetirizine (Zyrtec) is to treat allergy symptoms. In Phase II testing, it was tested in people with respiratory allergies to see if their symptoms improved without causing important side effects.
FDA Approval: Phase III -- To reach Phase III testing, a drug must be sufficiently safe in Phase II testing and show clear signs of being effective for a specific indication. Phase III trials usually involve about 1,000–3,000 people. At this stage, researchers better define the risks and benefits of the drug, its side effects, and how frequently the side effects occur, especially compared with other drugs used for the same disease. In short: How good is this new drug? Whom does it help? How much does it help? And what can go wrong?
One important goal of Phase III trials is to determine the circumstances under which the drug would be dangerous to prescribe. These conditions are called contraindications. For example, if a drug is somewhat toxic to the liver, it could be life threatening for a person with pre-existing liver disease. For this hypothetical drug, therefore, liver disease is a contraindication.
