FDA’s Risk Management Guidance To Be Harmonized With Europe, Japan

Risk management and risk assessment collaboration between the U.S., Europe and Japan will be one of the topics discussed at the International Conference on Harmonization in Brussels, Belgium from May 9-12.

One conference topic will be "ways of coordinating or collaborating between Europe, the United States and Japan on areas related to risk assessment and risk management," FDA Office of Pharmacoepidemiology and Statistical Sciences Director Paul Seligman said at a Drug & Device Dialogue web conference on "FDA's Final Risk Minimization Guidances: How Will They Impact Approval of Your Drug?"

[Editor's Note: The April 26 Drug & Device Dialogue audio conference on FDA's final risk minimization guidances is now available on CD. Contact F-D-C Reports at 800-332-2181 or visit ¹ www.drugdevicedialogue.com .]

Seligman believes FDA's recently released guidance for risk minimization action plans (RiskMAPs) puts the U.S. ahead of its European counterparts.

"In terms of our guidance on the development of a RiskMAP...we're at this point ahead of the Europeans," he said. "The Europeans in many respects are in the initial stages of developing some of their own approaches to risk management."

FDA's RiskMAP design is outlined in three guidances released March 24: "Development & Use of Risk Minimization Action Plans," "Premarketing Risk Assessment" and "Good Pharmacovigilance Practices & Pharmacoepidemiologic Assessment" (² (Also see "Risk Management Guidance Suggests Advisory Cmte Review For RiskMAPs" - Pink Sheet, 28 Mar, 2005.), p. 3).

The publication of the guidances fulfills a requirement under the prescription drug user fee reauthorization from 2002. FDA Acting Commissioner Lester Crawford also required the guidances to be completed as part of an agency-wide drug safety initiative.

In the EU, legislation revamping the approval pathway for prescription drugs requires sponsors to include pharmacovigilance plans in their marketing applications starting Nov. 20, 2005 (³ (Also see "EU Drug Applications Will Need Pharmacovigilance Plans In 2005" - Pink Sheet, 14 Feb, 2005.), p. 6).

In addition, the European Medicines Agency aims to publish a plan during the second quarter to further develop its risk management strategy (⁴ , p. 5).

Drug marketers that sell products in multiple regions could benefit from a consistent global approach on risk management.

"To date, there are no internationally agreed upon standards or criteria for assessing" whether an adverse event was caused by a drug in individual cases, FDA Office of Drug Evaluation III Deputy Director Julie Beitz said during the Drug & Device Dialogue.

U.S. and European definitions of pharmacovigilance are very similar, Beitz noted. The overriding message is that "the best method depending on the situation can vary....Both sides of the Atlantic encourage sponsors to meet with regulators to discuss what the best studies might be to address the specific concerns."

In the U.S., FDA's oversight of drug safety has been thrust into the spotlight over issues like antidepressant use in pediatric patients and the cardiovascular safety of COX-2 inhibitors.

Office of Drug Evaluation II Director Robert Meyer stressed the need for a better drug safety message to patients. "There is a need that the public better understand how drugs are optimally used and that drugs have safety issues attached to them....All drugs do."

"We often hear reference to a drug being safe or not safe. Safety is always a relative term, informed by the data on efficacy, safety and how the drug is used."

"The message [to the public] is something that is the shared responsibility of FDA and the industry...to make sure that the drugs that are approved are found safe and effective for their indication as labeled," Meyer said.

"That doesn't mean that the drug doesn't have any risk in its use. And to the degree that the public does not understand that from my perspective...is the shared responsibility of agency and industry."

FDA acknowledged that it has no mechanism by which to definitely determine whether a product has any unidentified safety issues. "I don't know that we have any absolute requirements about this," Beitz said. "I assume the companies are already reviewing some of the safety profiles of their products."