Genta, Inc (fka GNTAQ)

[The Holder]

Understanding "Bumps in the Road"

Bumps in the Road

If the FDA decides that the benefits of a drug outweigh the risks, the drug will receive approval and can be marketed in the United States. But if there are problems with an NDA or if more information is necessary to make that determination, the FDA may decide that a drug is "approvable" or "not approvable."

A designation of approvable means that the drug can probably be approved, provided that some issues are resolved first. This might involve the sponsor and the FDA coming to a final agreement on what should go on the drug's labeling, for example. It could also involve more difficult issues, such as the adequacy of information on how people respond to various dosages of the drug.

A designation of "not approvable" describes deficiencies significant enough that it is not clear that approval can be obtained in the future, at least not without substantial additional data.

Common problems include unexpected safety issues that crop up or failure to demonstrate a drug's effectiveness. A sponsor may need to conduct additional studies--perhaps studies of more people, different types of people, or for a longer period of time.

Manufacturing issues are also among the reasons that approval may be delayed or denied. Drugs must be manufactured in accordance with standards called good manufacturing practices, and the FDA inspects manufacturing facilities before a drug can be approved. If a facility isn't ready for inspection, approval can be delayed. Any manufacturing deficiencies found would need to be corrected before approval.

"Sometimes a company may make a certain amount of a drug for clinical trials. Then when they go to scale up, they may lose a supplier or end up with quality control issues that result in a product of different chemistry," says the FDA's Kweder. "Sponsors have to show us that the product that's going to be marketed is the same product that they tested."

John Jenkins, M.D., director of CDER's Office of New Drugs, says, "It's often a combination of problems that prevent approval." Close communication with the FDA early on in a drug's development reduces the chance that an application will have to go through more than one cycle of review, he says. "But it's no guarantee."

The FDA outlines the justification for its decision in an action letter to the drug sponsor. When the action is either approvable or not approvable, CDER gives the sponsor a chance to meet with agency officials to discuss the deficiencies. At that point, the sponsor can choose to ask for a hearing, or correct any deficiencies and submit new information, or they can withdraw the application.

http://www.fda.gov/Fdac/features/2002/402_drug.html