Ensuring Drugs Are Safe and Effective : Reviewing Applications

by Food and Drug Administration (FDA)

(Page 2 of 4)

Though FDA reviewers are involved with a drug's development throughout the IND stage, the official review time is the length of time it takes to review a new drug application and issue an action letter, an official statement informing a drug sponsor of the agency's decision.

Once a new drug application is filed, an FDA review team — medical doctors, chemists, statisticians, microbiologists, pharmacologists and other experts — evaluates whether the studies the sponsor submitted show that the drug is safe and effective for its proposed use. No drug is absolutely safe; all drugs have side effects. "Safe" in this sense means that the benefits of the drug appear to outweigh the risks.

The review team analyzes study results and looks for possible problems with the application, such as weaknesses of the study design or analyses. Reviewers determine whether they agree with the sponsor's results and conclusions, or whether they need any additional information to make a decision.

Each reviewer prepares a written evaluation containing conclusions and recommendations about the application. These evaluations are then considered by team leaders, division directors, and office directors, depending on the type of application.

Steven Hirschfeld, M.D., Ph.D., a medical officer in CDER's Division of Oncology Drug Products, says, "It is impossible to have all the information we wish to have at the time we need it." One factor is the practical size of clinical trials, which typically include several thousand subjects at the most.

"We are using information about past experience from a select group of people — those enrolled in particular clinical trials — and attempting to predict the future experience of the population at large."

For Hirschfeld, recognizing uncertainty and attempting to minimize it is one of the greatest challenges in reviewing information about health products. Recommending designs for clinical trials is one way to ask for more information and resolve unanswered questions, he says. Controlled clinical trials allow the FDA to conclude whether a new drug has shown substantial evidence of safety and effectiveness.

In Hirschfeld's opinion, some aspects of the job are similar to the responsibilities of air traffic controllers in the sense that they also analyze information that's available to them and make recommendations that can be acted on.

"People bringing planes in have to balance weather, other planes in the sky, ground traffic, and arrival and departure schedules, all without placing people at greater risk," he says. They can rearrange flight schedules and use different runways to lower the risk of problems, and the FDA can limit a drug's use or take other steps to lower the risk of problems, he says. "We all have responsibilities to protect or guide those who are vulnerable, and we use the best analytic tools at our disposal."

Reviewers receive training that fosters consistency in drug reviews, and good review practices remain a high priority for the agency. For example, CDER recently held a two-day retreat in which clinical reviewers discussed review priorities, including improved communication between drug review divisions in CDER regarding drugs being reviewed for more than one indication.

Sometimes the FDA calls on advisory committees made up of outside experts who help the agency decide on drug applications. Whether an advisory committee is needed depends on many things.

"Some considerations would be if it's a drug that has significant questions, if it's the first in its class, or the first for a given indication," says Mark Goldberger, M.D., director of CDER's office that evaluates drugs to treat infectious diseases and immunosuppressive agents. "Generally, FDA takes the advice of advisory committees, but not always," he says. "Their role is just that — to advise."

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.