Drug Approval Process

The process that a manufacturer of a new drug must undergo to gain approval by the United States Food and Drug Administration (FDA) is lengthy and complex. Drug companies seeking approval to sell a prescription drug in the United States must first test it to prove that it is safe and that it actually works. This is true for all drugs, even if the drug being tested is related in some way (as in a similar chemical structure) to one already approved and marketed for the same disease.

Sometimes, a drug that was developed to treat one disease may wind up being used for a totally different purpose by the time the drug development and clinical trial phases are completed. It can take up to 8-10 years or even longer for the development and human testing of a prescription drug before it is approved for sale in the United States by the FDA. The drug company and the FDA work very closely during this entire period of time and it is expected that the drug company will report all test findings, both good and bad to the FDA.

Early Testing

First, the drug company or sponsor must perform laboratory and animal tests to discover how the drug works and whether it’s likely to be safe and work well in humans. Most drugs that undergo preclinical (animal) testing never even make it to human testing and review by the FDA. However, if tests in animals do show that a prescription drug might be safe and work well, tests in humans begin but only after the company files an application with the FDA called the Investigational New Drug Application (IND). The IND describes how the manufacturer will test the drug in humans.

Testing in Humans

Drug studies in humans can begin only after an IND is reviewed by the FDA and a local institutional review board (IRB). The board is a panel of scientists and non-scientists in hospitals and research institutions that oversees clinical research in order to insure the safety of people participating in the clinical trial as well as how the study itself is designed. IRB’s make sure that people who enroll are fully informed about any risks that might occur as a result of participating in a clinical trial. This is called informed consent.

Clinical Trial Phases

Phase I trials

Phase I trials are the initial tests of a drug safety in humans. Commonly, these tests are performed in 20-80 healthy volunteers. Phase I tests determine how the prescription drug enters and leaves the body; how the drug changes the normal functions of the body; and, what side effects might occur as doses of the drug get higher and higher. If patients with a disease are tested in a Phase I trial, early evidence of whether the drug works to treat that disease can be collected. If a drug is considered to be safe and potentially effective in Phase I trials, it will be tested in Phase II trials.

Phase II trials

Phase II trials test whether the drug works in a particular disease or condition. Typically, 100 to 300 patients with that disease or condition are tested. These tests also find out the common short-term side effects and risks. At this stage of the development, if a prescription drug is considered to be safe and effective in patients with a particular disease or condition, the drug company and the FDA will together decide how it will then be tested in Phase III trials.

Phase III trials

Phase III trials are intended to compare the overall benefits of a drug to its common side effects or other potential risks in 1000 to 3000 patients with a particular disease or condition. If the benefits of the drug outweigh its risks, the results of these Phase III tests are submitted by the drug company to the FDA in the form of a New Drug Application (NDA). A team of FDA physicians, statisticians, chemists, pharmacologists, and other scientists review the company’s data, study results and proposed prescribing information, or labeling in order to move the prescription drug from development to approve. During this time, the FDA also makes sure that the drug company can manufacture the product safely and consistently. If this review establishes that a drug’s health benefits outweigh its known risks, the prescription drug is approved for sale.

Phase IV trials

Phase IV trials are performed after a prescription drug has been approved for sale in the US. These trials gather additional information on the benefits and optimal use of the drug in more real-life settings. In addition, because the drug is now being used in greater numbers of patients than those who were enrolled in limited clinical trials, Phase IV studies also likely to identify less common side effects. Frequently, the FDA and pharmaceutical manufacturers work jointly to perform additional effectiveness and safety trials after a drug has been approved, or the FDA may require that Phase IV studies be conducted after the drug is approved as a condition of approval.

Information on clinical trials being conducted for a wide range of prescription drugs and diseases in the United States and globally can be found at www.clinicaltrials.gov.

Written by: Teri Robert | Last reviewed: August 2014.