FDA Issues Five-Year Drug Safety Plan; Draft Plan Limited to So-Called “PDUFA IV Drug Safety Enhancement Resources”

Earlier this month, FDA announced the release of the Agency’s draft Prescription Drug User Fee Act (“PDUFA”) IV Drug Safety Five-Year Plan.  The draft plan is one of the goals FDA agreed to under PDUFA IV, which is the latest reauthorization of PDUFA that was enacted as part of the FDA Amendments Act (“FDAAA”) in September 2007.  Specifically, FDA agreed to prepare and implement “a 5-year plan to modernize drug safety, including improving communication and coordination between the post-market and pre-market review staff.” 

FDAAA Title I reauthorized PDUFA through Fiscal Year 2012 and made several changes to the law, including the broader use of user fee revenue to fund FDA’s drug risk management activities.  Since the enactment of PDUFA in 1992, FDA has only been authorized to use user fee revenues “for the process for the review of human drug applications.”  PDUFA III, enacted in 2002, first expanded the definition of “process for the review of human drug applications” in FDC Act § 735(6) to include “collecting, developing, and reviewing safety information on [drugs approved after October 1, 2002], including adverse event reports, during a period of time after approval of such applications or supplements, not to exceed three years.”  PDUFA IV further expands the range of postmarket activities (without any temporal limitation) for which user fees revenues can be expended by adding the development and use of “improved adverse-event data-collection systems,” “improved analytical tools to assess potential safety problems,” and enforcement of new provisions of the FDC Act added by FDAAA into the definition of “process for the review of human drug applications.”   

Under PDUFA IV, $29.29 million (plus an annual inflation factor) in user fee revenue is to be used by FDA for drug safety activities – specifically the negotiated drug safety commitments identified in the goals letter accompanying PDUFA IV.  FDA refers to this funding stream as “PDUFA IV drug safety enhancement resources.”  In addition to the $29.29 million, FDAAA authorized FDA to collect additional user fees ($25 million in Fiscal Year 2008, increasing annually to $65 million in Fiscal Year 2012) to broaden the focus of drug safety.  FDA refers to this funding stream as “FDAAA authorized resources.”  FDA believes that “Congress intended these additional resources to increase the Agency’s capacity for handling new authorities and requirements of FDAA, including (as examples) efforts associated with implementing Risk Evaluation and Mitigation Strategies (REMS), Post-Market Study/Trial Requirements, Safety Labeling Changes, Active Postmarket Risk Identification, and other provisions.”  At this time, FDA’s draft safety plan focuses only on “PDUFA IV drug safety enhancement resources.”  However, FDA intends to update the draft plan periodically (not less than annually), and a future plan will reportedly include the Agency’s strategies for spending the additional “FDAAA authorized resources.”

FDA’s PDUFA IV drug safety commitments identify several goals, including: (1) strengthening management and operations; (2) improving collection and analysis of adverse event data; (3) implementing epidemiology best practices; (4) expanding database acquisition and use for targeted post-marketing surveillance and epidemiology; (5) strengthening risk management and communication tools; (6) improving post-market information technology systems; and (7) increasing timely, consistent review of new drug trade names to prevent confusion. 

FDA’s draft safety plan discusses the Agency’s strategies for meeting each of these commitments. For example, to strengthen FDA’s management and operations, the Agency will significantly expand the Office of Surveillance and Epidemiology in the Center for Drug Evaluation and Research by hiring additional staff.  FDA notes, however, that the effects of a staff increase might not be immediately felt, because “[t]ypically, it takes at least two to three years of intense training to prepare new staff to be seasoned in drug regulation.”  Some of FDA’s strategies are not new, but rather, expand on previous proposals.  For example, while FDA notes in the draft plan that the Agency will be holding a public workshop in May 2008 on developing guidance on conducting scientifically sound pharmacoepidemiologic safety studies, FDA floated the idea of developing and issuing guidance on epidemiology best practices in the Agency’s January 2007 report responding to the to the Institute of Medicine’s September 2006 report September, titled The Future of Drug Safety: Promoting and Protecting the Health of the Public.

By Kurt R. Karst