FDA will track Phase IV safety studies through a new Office of Post-marketing Drug Risk Assessment, Center for Drug Evaluation & Research Deputy Director for Review Management Murray Lumpkin said in a memo to FDA employees Dec. 23.

The formation of the new office represents CDER's first organizational response to the FDA reform/user fee reauthorization law. As part of its post-marketing surveillance duties, OPDRA will be responsible for tracking Phase IV study commitments relating to safety questions, Lumpkin indicated. The review divisions will likely be responsible for tracking other types of Phase IV studies. The FDA Modernization Act signed in November mandates tracking and reporting the progress of Phase IV studies ("The Pink Sheet" Nov. 17, 1997, p. 14).

CDER's Division of Pharmacovigilance and Epidemiology (within the Office of Epidemiology and Biostatistics) will be transformed into the new office over the next six to eight months, Lumpkin said. The office will include two Divisions of Drug Risk Assessment, DDRA1 and DDRA2.

The director of the new office will report to Lumpkin. The agency will advertise internally and externally for a permanent office director, a deputy office director and division directors in January. The remaining biometric portion of the present Office of Epidemiology and Biostatistics will become part of a renamed Office of Biostatistical Sciences that will continue to be headed by Director Robert O'Neill, PhD, Lumpkin's memo adds.

"Once the new leadership is selected and in place," Lumpkin said, "we will implement the new office structure. Until that time, while we are transitioning to the new office, DPE will continue to function as a division of OEB as at present."

Ralph Lillie will be DPE's acting director during the transition period. Lillie was previously a project manager in the Center for Drug Evaluation and Research director's office, where he has been involved in acceptance testing of the Adverse Events Reporting System.

A transition team consisting of Lumpkin, O'Neill, Lillie, OEB Associate Director Bob Nelson, PhD, Review Management Senior Manager Bill Oswald, and a representative from each of the three present branches in DPE "will be responsible for the overall coordination of the work and various efforts of DPE during its transition," Lumpkin said. Nelson plans to retire at the end of January.

"Yet to be determined is the extent of the info tech support in the new office required to maintain contracts, interactions with [the office of Information Technology], data entry, and daily services of the [software]," the memo states. "Obviously there will be a need for this service within the new office (most likely as a group reporting to the director), but the details of this will need also to be worked out during the transition period." Lumpkin said DPE is expanding its staff by 10 employees, to a total of 68, in fiscal 98.

The reorganization will be funded out of FDA's appropriated budget. FDA Lead Deputy Commissioner Michael Friedman, MD, said at a CDER seminar in November that FDA "tried very hard" to have additional funding under the Prescription Drug User Fee Act for Phase IV surveillance. Friedman suggested that the agency needs to implement an efficient and effective post-marketing surveillance system throughout the agency before it can receive funds for the activity ("The Pink Sheet" Nov. 10, p. 5).

"With more products being developed well and more expeditiously (and thus more approved expeditiously), the imperative to have an outstanding system of post-marketing drug risk surveillance, assessment and management is all the greater," Lumpkin said. FDA approved 39 new molecular entities in 1997 .

The importance of post-marketing surveillance will be emphasized by raising DPE to "office" status, Lumpkin suggested. In addition, DPE's growing responsibilities in operating the electronic Adverse Events Reporting System and ongoing development of guidances to implement the International Conference on Harmonization agreements on adverse event reporting make the timing right to reorganize, Lumpkin said.

"Presently going through the final stages of acceptance testing, we will continue to transition our info tech and basic analytical processes to this new AERS system throughout FY98," the memo says. Besides hiring OPDRA's leadership, getting the AERS in final working order is one of the transition team's top priorities, Lumpkin said. OEB Surveillance and Data Processing Branch Chief William Calvert told a recent FDA/Food & Drug Law Institute meeting that FDA expects AERS to be "up to full performance" by early January ("The Pink Sheet" Nov. 24, T&G-14).

"With the implementation of several ICH risk assessment process agreements, much more will be required and expected of our post-marketing drug risk assessment staff," Lumpkin noted, including reviewing post-marketing safety update reports; "defining further the content of PSURs as situations arise; more analytical surveillance using the tools in AERS; more feedback to companies regarding the adequacy of their PSURs; and more proactive and seamless risk assessment `strategizing' with the pre-market review divisions including Phase IV safety studies."

Post-marketing adverse event data will be reviewed by teams of experts from different disciplines similar to the way INDs or NDAs are reviewed.

Under the new structure, OPDRA's "epidemiologists and risk assessors will be combined into drug risk assessment teams within the new divisions," Lumpkin said. The teams will be assigned specific drugs for post- marketing signal analysis. Lumpkin said that to start, drugs will be divided evenly between OPDRA's division on a numerical basis, although in the future, the divisions could become more closely linked to specific review offices.

"As with the review teams within the [Offices of Drug Evaluation], it is expected that members of these risk assessment teams in the new divisions will bring their individual discipline expertise to the overall process of assessing the new risk data," Lumpkin continued.

The divisions "will not only concern themselves with review activities related to post-marketing risk assessment," Lumpkin added. "It is expected that they will also be actively involved with their biometric colleagues in exploring and defining new methodologies and quantitative approaches to investigating post-marketing safety concerns."

"In addition, the new office and divisions will be responsible for maintaining and utilizing our various cooperative agreements with various epidemiologic databases and in maintaining our partnerships with our post-marketing risk assessment colleagues in other drug regulatory agencies," the memo says.

FDA OFFICE OF POST-MARKETING DRUG RISK ASSESSMENT WILL TRACK PHASE IV SAFETY STUDIES; TWO DRUG RISK DIVISIONS WILL DIVIDE NME WORKLOAD, TRACK DRUGS IN TEAMS

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