Warnings to device makers up in '01; drug warnings flat despite spike in recalls.

Dear Reader,

Warning letter counts for the first half of fiscal year 2001 suggest that little has changed for most centers at FDA in its output of the mechanism despite pilot programs designed to suppress the counts.

The agency's Center for Drugs had knocked out 67 warning letters at the midpoint in FY '01 as compared to a total of 130 in the preceding year. By the same date, the Center for Biologics had issued 23, a figure that roughly keeps pace with the full year's count of 43 in FY '00. CDER letters include those for medical gases.

The Center for Devices, however, has used substantially more toner than last year. In the first six months of FY '01, CDRH cranked out 414 warnings compared to 528 in all of last year. Of this year's count, 317 letters were addressed to mammography clinics (the total for last year's mammography letters was not available at press time).

Among the letters from CDER to drug makers was a warning (Doc. 9955W) from the Division of Drug Advertising, Marketing and Communication (DDMAC) to Pharmacia for promotional activities undertaken on the firm's behalf by a physician who took in an untitled letter of his own (Doc. 9957W) from DDMAC.

The warning letter cited "repeated" promotions that minimized the risks involved in concurrent use of Celebrex (celecoxib) and Coumadin (warfarin) and suggested CDER had grown tired of talking to the firm about the promotion.

Joseph Famulare, director of the Division of Manufacturing and Product Quality at CDER, stated recently that drug recalls reached an all-time high in FY '00, a trend running counter to the lower number of warning letters issued after a peak of 258 in FY '98. Of the 472 recalls this past fiscal year, 352 were for prescription drugs and industry left it to others to uncover the defects in all but 181 of the recalls.

Conspicuous in its absence is any warning letter to Schering-Plough for the inspection of its plant in Kenilworth, NJ, also site of the firm's headquarters. The inspection ran from November 2000 to January and gave birth to an 18-page 483 that Public Citizen Health Research Group obtained and released, garnering Schering lots of bad ink and a black day on Wall Street in February. The inspection is reviewed in the April issue of "Inspection Monitor," published by the Washington Information Source Co.

FDA has relented from its issuance of letters constituting "Notice of Initiation of Disqualification Proceedings and Opportunity to Explain" (NIDPOE) letters. CDER punched up three in FY '00 and CBER wrote two, but only one has gone out since Oct. 1, 2000, addressed to James Wilson, M.D., of the Institute for Human Gene Therapy at the University of Pennsylvania. CBER alleged that prospective subjects were "misled" as to the agency's involvement in dose escalation of an unnamed study and that Wilson did not let FDA in on amendments to the protocol that allowed grade III toxicities. Wilson also took a hit for failing to exclude an unspecified number of subjects for elevated antibody titers.

This issue of "Warning Letter Bulletin" includes no warning letters to drug manufacturers, an unusual outcome. On the other hand, FDA wrote up eight device makers in the weeks of April 9 and 16 as well as 16 letters to dairies and feed mills.

Six feed mills were cited for deviating from regulations promulgated to stem the tide of Mad Cow disease, a.k.a. bovine spongiform encephalopathy. This disease has driven much of the regulatory action in this area since the beginning of the year. Whether hoof-and-mouth disease will generate a similar outpouring of ink remains to be seen.

Sincerely,

The Editors