How the FDA Drug Approval Process Works

March 16, 2012 | 1:31 pm
Francesca Grifo
Former contributor

Earlier this week, my colleague Michael gave some general background on the Food and Drug Administration and what Congress has to do this year to ensure that the agency can continue to ensure the safety and efficacy of prescription drugs and medical devices. In reading the post, I reflected back on my time leading a program at NIH dedicated to finding new drug compounds in nature, preserving the biological diversity that makes new discoveries possible, and strengthening the ability of developing companies to do such research.

I thought the enormous complexity of the drug discovery and development process warranted an explanation. So how exactly does the FDA make sure that new commercial products are ready for you?  Here’s what happens:

Step One: Initial development and testing

Living things and synthetic compounds supply the materials that may be effective in treating illness and injury in humans. Scientists explore various substances, many of which turn out to be dead ends. This initial research should demonstrate that a potential new drug is reasonably safe for initial use in humans, and that it holds some potential for treatment.

Western Yew

Nature provides us with many molecules that can help humans fight disease. The bark of the Pacific yew contains paclitaxel (brand name Taxol), a drug that is used to treat ovarian cancer. It is important to protect our world’s biodiversity so scientists can continue to discover these kinds of compounds. Photo: Flickr user brewbooks

Step Two: Application for testing in humans

Armed with promising results, drug developers submit an Investigational New Drug application to FDA’s Center for Drug Evaluation and Research (CDER) in which they propose “clinical trials” that will expose humans to the potential drug for the first time in limited and highly regulated ways. The application should contain pharmacological and toxicological data derived from animal studies and, if available, information on previous use in humans (often in other countries). The application also should include information about how the drug will be manufactured, who the investigators are, and how the investigators will conduct the clinical trials.

The FDA has 30 days to review the application and raise any red flags. The FDA can also stop clinical trials at any point if the agency sees problems.

Step Three: Clinical trials

The investigators conduct clinical trials in three initial phases described here. Data from these three stages are used to prepare a drug for evaluation.  Phase I trials are conducted on a very small group of healthy and non-healthy people to evaluate safety, dosage, and side effects. Once changes are made based on Phase I results, more sick people are exposed to the drug in Phase II to evaluate effectiveness and further understand side effects. If the second phase of trials demonstrates adequate effectiveness,  Phase III begins, which is designed to help reviewers determine whether the benefits of the drug outweigh the risks.

Step Four: Application for drug approval

If the clinical trial data is promising, the drug’s sponsor submits a New Drug Approval application to the FDA. In addition to the data, the application includes information about how the drug will be manufactured, proposed dosage, and proposed packaging and labeling.

Step Five: Evaluation of application

Under the Prescription Drug User Fee Act (PDUFA), the agency has ten months to review the application. CDER scientists review the data and proposed labeling. If they determine that the drug’s benefits outweigh its known risks, the drug is approved for sale.

Step Six: Post-market monitoring

Data from a fourth stage of clinical trials is collected after a drug is approved to refine its use. The FDA monitors a drug’s safety and efficacy by maintaining a program called MedWatch that allows the reporting of adverse side effects. Many believe that the FDA does not have adequate resources to carry out effective post-market monitoring.

Step Seven: Development of generics

When the patent on a new drug expires, manufacturers apply to FDA to develop generic versions of the drug.

The FDA has a decent summary of how this process worked to develop a new drug to prevent osteoporosis.

Both industry and FDA make big investments in this process. Both have enormous stakes in the outcome. This is why it behooves us to build in safeguards that ensure the process works and stays true to the science. This includes more transparency in the way FDA makes drug approval decisions. This also includes retaining and increasing limitations on conflicts of interest for the scientists who serve on supposedly independent scientific advisory committees that are set up to give advice to FDA on the safety and efficacy of new drugs.

These challenges can be met through the work of Congress to reauthorize the legislation that governs the drug approval process and by the FDA improving and fully implementing its scientific integrity policy.