FDA And EMEA To Compare Regulatory Approaches Used In 1998 NME Cohort

FDA and the European Medicines Evaluation Agency will conduct a joint assessment of the approaches used by the two agencies in the 1998 cohort of new molecular entity reviews.

The project will investigate "what, if any, differences there were in the questions and issues [FDA] raised on the applications and the questions and issues raised by the EMEA" about the products.

FDA Center for Drug Evaluation & Research Deputy Director for Review Management Murray Lumpkin, MD, will conduct the research during a three-month sabbatical at the EMEA this summer.

Lumpkin said in a memo to CDER staff that he plans to participate as "a part of daily life" at EMEA, which will include observing the development of guidance documents and sitting in on meetings of EMEA's Committee for Proprietary Medicinal Products and the CPMP's Pharmacovigilance Working Party.

Lumpkin has coordinated his visit primarily with EMEA New Chemical Substances Head of Sector Patrick Le Courtois.

The project will look at how FDA and EMEA emphasize product review disciplines differently during the approval process and will attempt to determine reasons for any differences in regulatory action.

For applications that were approved by both agencies, Lumpkin plans to compare the U.S. and European labeling for the product in order "to see how both institutions tried to communicate the information about and issues with the product."

"I hope that this will ultimately allow us both to compare and contrast how we both approach and accomplish the drug oversight jobs we both have," Lumpkin said.

Lumpkin's analysis will focus on products submitted in 1998, the last cohort for which FDA has completed first actions. The cohort includes about 35-45 drugs.

In terms of product approvals, FDA has been more productive in recent years. In 1998, for example, FDA cleared 30 NMEs compared to 17 approved by EMEA.

Of the 17 drugs approved by the European agency during the study year, FDA approval preceded European clearance for 13 of the applications.

Only four of the 1998 drugs - Roche's Xenical, Sonus' Echogen and Novartis' Comtan and Exelon - were cleared by EMEA before FDA approval. FDA approved Xenical only in April 1999, Comtan in October 1999 and Exelon in April 2000. Echogen, first filed in August 1996, is still pending at FDA.

Post-marketing experience with the products will likely be an area of comparison for the assessment. FDA's 1998 approvals did not include any drugs that have been subsequently withdrawn in the U.S. Roche's COMT inhibitor Tasmar, however, has been withdrawn in Europe and relabeled in the U.S. following reports of liver toxicity.

Other drugs approved by FDA in 1998 that subsequently required safety-related labeling changes include Glaxo Wellcome's Ziagen, Pfizer's Viagra and Merck's Singulair.

FDA's 39 NME approvals in 1997 included a number of drugs which have since been withdrawn: Warner-Lambert's Rezulin and Wyeth-Ayerst's Duract due to liver toxicity; Roche's Posicor due to drug interactions and cardiac toxicity; and Glaxo's Raxar due to cardiac adverse events.

Other 1997 approvals, including Pfizer's Trovan and Pharmacia's Mirapex, required safety-related labeling changes. Trovan use has been sharply restricted.

Public Citizen's Health Research Group has highlighted the 1997 NME class as evidence that the increased productivity at FDA has led to decreasing emphasis on product safety (¹ (Also see "FDA Defends Approvals After Divided Advisory Committee Votes In JAMA" - Pink Sheet, 10 Jan, 2000.)).

During Lumpkin's sabbatical, Office of Drug Evaluation IV Director Dianne Murphy will serve as Office of Review Management acting director.

Murphy recently concluded another temporary assignment in an FDA leadership position, serving as associate director for pediatrics for a one-year detail that ended in March.

The pediatric position was a high-profile role in FDA as the agency began to administer the pediatric exclusivity provisions of the FDA Modernization Act. Pediatric health issues have been a focus of the White House, with First Lady Hillary Clinton sponsoring several forums on aspects of childhood development.

FDA has created a science director position for pediatrics. Children's National Medical Center Infectious Diseases Chairman William Rodriguez, MD/PhD, will join the agency in July and focus on the science and research issues that resulted from the implementation of FDAMA and the pediatric rule.

Murphy rejoined FDA as ODE IV director from the University of Florida in 1998. She had previously served on the agency's antiviral drugs advisory committee and worked as assistant director of medical affairs in FDA's antiviral drug division from 1990 to 1993.

Murphy will be assisted as director of ORM by Office of Review Management Senior Management Officer William Oswald, who will handle administrative issues. Office of Medical Policy Director Robert Temple, MD, will continue to be responsible for specific product decisions or disputes with policy implications.

Office of Drug Evaluation IV Deputy Director Sandy Kweder, MD, will fill in for Murphy as acting director of ODE IV. Kweder already has experience directing ODE IV, after serving in the position during Murphy's pediatric assignment.

Office of Review Management Deputy Director Solomon Sobel, MD, will continue with his duties.

ORM did not have a deputy director position before Sobel assumed the role (² (Also see "FDA ODE II Overhaul Continues: Rarick Returns, Sobel Moves Up" - Pink Sheet, 20 Dec, 1999.)). Sobel had previously served as Endocrine & Metabolic Drug Products Division director.

Lumpkin was a candidate for the Center for Devices & Radiologic Health director position after Bruce Burlington, MD, joined Wyeth-Ayerst as senior VP-regulatory affairs (³ (Also see "FDA Pulmonary Division Director Jenkins To Head ODE II; Bilstad To Head QA" - Pink Sheet, 26 Apr, 1999.)).

Former Center for Biologics Evaluation & Research Medical Deputy Director David Feigal is now CDRH director. CDRH Deputy Science Director Elizabeth Jacobson, who served as acting center director following Burlington's departure, has been named acting senior advisor for science in the Commissioner's office (⁴ (Also see "FDA Calls Off Deputy Commissioner Search; Jacobsen Named Senior Advisor" - Pink Sheet, 5 Jun, 2000.)).