Legislation marks significant boost to FDA post-market safety efforts.

WASHINGTON -- The Food and Drug Administration Amendments Act (FDAAA) 2007 is a "significant change in the regulatory paradigm," Center for Drugs Deputy Director Douglas Throckmorton, M.D., told the Food and Drug Law Institute (FDLI) annual meeting here March 27.

Particularly important changes occurred in the area of post-marketing safety, Throckmorton said. The legislation clarifies roles and responsibilities for parts of CDER and "rebalances the Center's efforts and resources devoted to drug development and post-market drug safety."

FDAAA 2007 expands safety review and pharmacovigilance efforts and allows the use of fees to fund drug safety activities without any date restrictions. It "builds on previous legislative actions to make drugs available that have significant adverse effects," Throckmorton said.

Throckmorton noted a recent "Federal Register" notice published in March that identified 16 drugs and biologics that FDA determined have an approved risk evaluation and management strategy (REMS) in place. FDAAA 2007 "notifies the holders of applications for such drugs of the Sept. 21, 2008, deadline for submitting a proposed REMS."

REMS will be used judiciously, he cautioned, and are not needed for all drugs. "Too many REMS would increase confusion in the system, could increase errors and decrease availability."

Throckmorton added that use of REMS:

* Must be commensurate with the specific serious risk listed in the labeling;

* Not be unduly burdensome on patient access to the drug; and

* To the extent practicable, conform with other elements for other drugs with similar serious risks and be compatible with established distribution, procurement and dispensing systems for drugs.

Regarding safety labeling changes, the legislation provides new authority for FDA to require labeling changes based on new safety information.

He noted that there are strict timelines for negotiating changes, and this is "part of a larger effort to engage earlier on efficacy and safety issues as they arise during the drug life cycle."

On post-marketing safety studies, Throckmorton said that "FDA may require studies at the time of approval, or after approval, based upon new safety information, limited to specific purposes," which include:

* To assess a known serious risk related to the use of the drug involved;

* To assess signals of serious risk related to the use of the drug; and

* To identify an unexpected serious risk when available data indicates the potential for a serious risk.

"Before requiring a clinical trial, FDA must find that adverse event reporting data from active post-market risk identification and analysis systems, and/or a post-approval epidemiology study or studies will not be sufficient," said Throckmorton. The apparent intent, he said, is to give FDA authority to obtain information in selective situations.

In pharmacovigilance, FDAAA "promises additional resources to address the dramatic increase in adverse event reporting and to monitor drugs." It also calls for expanded access to important population databases for both additional epidemiologic research and targeted safety surveillance.

This is "an enormous task with great promise and an ambitious timeline," he stressed.

Changes are needed in CDER personnel, and additional work is needed in the science of epidemiology and pharmacovigilance, Throckmorton stated. Also necessary is additional work on the IT systems needed to link disparate databases together and analyze their data meaningfully

He said the impact of the legislation may likely take "some time" to understand, but noted FDAAA 2007 includes new authorities, extensive new processes and procedures, as well as new timelines and expectations.

"Congress and the public are paying attention to what happens. Many of the changes mirror advanced work that is ongoing," he said.

By Joseph Pickett, AER staff