How Drugs get Approvd by the FDA

Contributed by: Michael Rafii, M.D., Ph.D - Director of the Memory Disorders Clinic at the University of California, San Diego.

Before a drug can be approved for use by patients, there is a set of clinical tests that must be performed. There is the Pre-Clinical Research Stage. Here the drug is synthesized and purified. Animal tests are performed, and institutional review boards assess the studies and make recommendations on how to proceed. If the recommendations are positive, then an application to the FDA occurs and clinical tests in humans may begin.

Phase 1: Clinical studies in this phase represent the first time that an Investigational New Drug (IND) is tested on humans, either healthy volunteers or patients. The purpose of these studies is to look at the metabolism and any potential side effects of the drug in humans. Phase 1 studies are usually conducted on 20 to 80 subjects and are therefore concerned with safety and tolerability.

Phase 2: The purpose of phase 2 is to determine the efficacy of a drug to treat patients with a specific disease or condition, as well as learn about common short-term side effects or risks. These studies are conducted on a larger scale than phase 1 studies and typically involve several hundred patients.

Phase 3: These trials provide even more information about the effects and safety of the drug, and more importantly assess the efficacy or the drugs ability to treat the disease. Phase 3 studies generally involve several hundred to several thousand people and can last from months to a couple of years. These trials are almost always double-blind and placebo controlled. This means that neither the subjects nor the researchers know who is getting the investigational drug versus placebo (or sugar pill).

There are several checks and balances in the process of clinical trials; among them is the use of institutional review boards (IRBs) and advisory committees. IRBs are designed to protect the rights and welfare of people participating in clinical trials both before and during the trials. IRB's are made up of a group of at least five experts and lay people with diverse backgrounds to provide a complete review of clinical proceedings. Also, clinical trials are monitored for their entire duration by study monitors and safety monitoring boards that follow subjects in real time as trials progress.

The Application Process:
Once a trial is complete, or closed, the data is then analyzed by statisticians and researchers to look for efficacy. Since many trials are multi-center, this process can take many months, the results of which are eventually submitted in a formal application to the FDA for final approval. This New Drug Application (NDA) must include results and analyses from tests of the drug on both animals and humans. The NDA must provide enough detailed information for FDA reviewers to make several critical decisions. The result of the study must show whether the drug is safe and effective and whether its benefits outweigh its risks.

The process of developing and testing a new drug is a lengthy one. The FDA estimates that it takes a little over 8 years to test a drug, including early laboratory and animal testing, before there is final approval for use by patients.

FDA Approval
The FDA's decision whether to approve a new drug for marketing comes down to answering two questions:
1. Do the results of blinded, placebo-controlled studies provide substantial evidence of its effectiveness?
2. Do the results show that the product is safe under the explicit conditions of use in the proposed labeling? Here "safe" is a relative term; it means that the benefits of the drug appear to outweigh its risks.
When the review is complete, the FDA writes to the applicant to say the drug is either approved for marketing, is "approvable," provided minor changes are made, or is not approvable because of major problems.


  1. Thank you for breaking this down. I have often read about drugs in a certain phase of development but never really understood what that meant with regards to when it would be available. This is brilliant.

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