Understanding drugs and their effects on human health

FDA Drug Approval Process

In order for a pharmaceutical company to obtain FDA approval for a new drug, a long sequence of detailed testing and clinical trials must be administered. The approximate cost of putting a new drug through the approval is $500 million, and it takes an average of fifteen years for a drug to make it from initial testing to being available for patients. Furthermore, of every 5000 compounds that go through pre-clinical testing, only five advance to the human testing phase, and only one of these compounds will actually be approved. There are six key phases of testing that potential drugs go through on the path to FDA approval. These phases are early research / pre-clinical testing, clinical trials (phase I, phase II and phase III), FDA approval, and post-marketing testing.

The first phase of the drug approval process is pre-clinical testing. This consists of laboratory and animal testing to demonstrate biological activity of the new drug against the targeted disease. The safety of the new drug is also assessed in the pre-clinical phase. This initial phase generally takes about 6.5 years to complete

After completion of the pre-clinical phase, the drug company files an Investigational New Drug Application (IND) with the FDA in order to begin testing the drug on humans. The IND outlines information known so far about the new compound and how new studies will be conducted. The Institutional Review Board where the studies will take place must review and approve the IND, and annual progress reports must be sent to the FDA.

The next phase is clinical trials. Volunteers in all three phases of the clinical trials must give informed consent before participation. Participants must know that the drug is investigational, understand risks involved, know their right to decline participation, and understand the pay incentive involved. In phase I, 20 to 80 healthy volunteers are used to test the drug over a 1.5-year period. This phase further tests the drug's biological and chemical activity as well as its safety profile, including safe dosage range. Phase II of clinical trials follows, in which 100 to 300 patient volunteers with the targeted disease are tested to evaluate the new drug's effectiveness and to determine any possible side effects. This phase takes approximately 2 years to complete. In phase III of clinical trials 1000 to 3000 patients with the targeted disease are studied for approximately 3.5 years. The large number of volunteers used in this phase minimize error caused by variable courses of the disease, observer bias, placebo effect, double or triple blind studies, or hidden toxicities. Tests in this phase confirm effectiveness of the new drug, and long-term use is monitored to determine any adverse reactions.

After all three phases of clinical trials have been completed, the company analyzes the data collected thus far and, if the data show effectiveness and safety, files a New Drug Application (NDA) with the FDA. The NDA is generally an immense document that must contain all of the detailed scientific information known about the drug up to this point. In 1996, the average review time for new drugs approved was almost 1.5 years.