REMS frequency seen increasing under FDAAA 2007, former chief counsel says.

ARLINGTON, VA -- Risk evaluation and management strategies (REMS) are expected to increase under the FDA Amendments Act of 2007 (FDAAA), a former chief counsel of FDA told a CBI conference here March 10.

Sheldon Bradshaw, now with the Washington office of Hunton & Williams, said Congress "significantly expanded FDA's authority over the post-market safety of drugs and biologics, including the authorization of FDA to require sponsors to conduct postapproval studies and clinical trials."

Bradshaw said the agency can now "order sponsors to make changes to a drug's label based on new safety information." He said Congress patterned REMs, in part, after several guidance documents previously issued by FDA.

"As such, the concept isn't entirely new. What is potentially new, however, is the frequency at which REMs will be imposed. In the past, risk management plans were only used when the drug posed a significant risk," he said.

Bradshaw said that under FDAAA 2007, FDA may order the development of REMs when it is necessary to ensure that the benefits of a drug outweigh its risks. And, FDA may request a REMS from the holder of an approved NDA or BLA if:

* The holder is seeking approval of a new indication, or

* FDA obtains new safety information and determines that a REMS is necessary to ensure that the benefits of the drug outweigh its risks.

In determining that a REMS is necessary, FDAAA specifies that FDA should consider:

* The estimated size of the population likely to use the drug;

* The seriousness of the disease or condition treated with the drug;

* The expected benefit of the drug with respect to the disease or condition;

* The expected or actual duration of treatment with the drug;

* The seriousness of any known or potential adverse events that may be related to the drug and the background incidence of such events in the population likely to use the drug; and

* Whether the drug is a new molecular entity. In the area of drug safety, Bradshaw said, FDA also is authorized to require a post-approval study or trial to:

* Assess a known serious risk related to the use of the drug;

* Assess signals of serious risk related to the use of the drug;

* Identify an unexpected serious risk when available data indicate the potential for a serious risk.

After a drug or biologic has been approved, FDA may order a study or trial only if the agency becomes aware of new safety information.

Under drug labeling, said Bradshaw, the FDAAA says that FDA now has explicit authority to mandate labeling changes based on "new safety information. "While the new authority (and the accelerated review process) certainly gives FDA additional leverage when negotiating with industry, FDAAA did not change the regulatory standard for adding a warning," he added.

Under the physician labeling rule, labeling may be revised to include a warning about a clinically significant hazard only if "there is reasonable evidence of a causal association with a drug."

Joseph Pickett, Associate Editor