WASHINGTON _ The FDA approved 22 new drugs and one newbiologic in 1994, down from 25 drugs and four biologics in 1993,according to a report released on Wednesday by the PharmaceuticalResearch and Manufacturers of America (PhRMA).

The figures account only for approval of "novel" molecular andbiologic agents and do not include other FDA approvals (such asvaccines) or actions.

PhRMA President Gerald Mossinghoff noted that while 1994 "wasnot a record year for new drug approvals," average review times atthe FDA are decreasing. The average time it took for the FDA toapprove a new drug in 1994 was 19.7 months, down from 26.5months in 1993 (a 26 percent reduction). For drugs under the aegisof the user fee program, the average review time was 12.9 months.The one biologic approved in 1994 that PhRMA counts as "novel"_Centocor Inc.'s ReoPro _ was reviewed by the FDA in 12 months.

The FDA released its own drug approval statistics on Tuesday,crediting its shorter review times to the 1992 Prescription Drug UserFee Act (PDUFA). According to the FDA's calculations, the mediantime it took the agency to approve 23 vaccines and other biologicalproducts in 1994 was 12.2 months, down from a median of 23.4months in 1993. The median time for the 62 drug approvals made in1994 was 19 months.

The FDA's median review time for the 22 drugs classified as "newmolecular entities"_ the same drugs that PhRMA focused on in itsreport _ was 17.5 months in 1994. FDA and PhRMA statisticsdiffer due to the fact that the agency uses "median approval times"while PhRMA uses "adjusted average review times." Generallyspeaking, the median does not capture the extremes of a given dataset (i.e., a drug that took 10 years to approve), while an average (themean) does. At the same time, averages can be "skewed" byextremes.

Despite the good news on FDA review times, George Rathmann,chairman and CEO of ICOS Corp., charged on Wednesday that theFDA's "zero-risk" requirements for the approval of new biologics isthreatening U.S. leadership in biotechnology. Noting the singlebiologic approval in 1994, he urged the Clinton Administration to"come to grips" with the "biotechnology product approval problem"at the FDA.

"In 1994, the Center for Biologics Evaluation and Research [CBER]had a staff of 776, but only one new therapeutic biologic wasapproved," said Rathmann. "The FDA . . . said it had eliminated its[biologics] backlog. And yet, only one new therapeutic biologic wasapproved last year. We are concerned that so many applications didnot result in approvals. This suggests a breakdown in the system."

However, CBER director Kathryn Zoon said last July that a majorityof the backlog applications were actually withdrawn by theirsponsors. Further, the vast majority of backlogged applications weremanufacturing supplements _ documents which do not result indrug approvals. "The high number of withdrawals suggests that therewere a lot of old dogs at the center," Zoon said in a speech sponsoredby the Food and Drug Law Institute. "There were very fewapprovables in the backlog cohort."

Zoon said that CBER had a backlog as of Oct. 1, 1992, of 26 ProductLicense Applications (PLA), 25 Establishment License Applications(ELA), six effectiveness supplements and 232 manufacturingsupplements. Between October 1992 and June 1994, more than 60percent (16) of the 26 backlogged PLAs at CBER were withdrawnby sponsors, two were approved by the FDA, three were deemed"not approvable" by the agency and three were classified as "other."That left two PLAs in the backlog. Likewise, 72 percent (18) of the25 backlogged ELAs were withdrawn by the sponsors, four weredeemed "not approvable" and three were classified as "other." (PLAsand ELAs must be filed simultaneously for biologics.)

About half (121) of the 232 backlogged manufacturing supplementsat CBER were withdrawn by sponsors, 38 were approved by theFDA, 49 were deemed "not approvable," and 25 were classified as"other." Only one out of six backlogged effectiveness supplementswas approved, while five (83 percent) were deemed "notapprovable."

PLAs Are On The Decline

The number of PLAs submitted to CBER is on the decline. In fiscal1993, 10 were submitted (the FDA's fiscal year runs from Oct. 1 toSept. 30), while fiscal 1994 saw eight new PLAs. Three-and-a-halfmonths into fiscal 1995, only one has been submitted. "While thenumbers of INDs are continuing to increase, the INDs are nottranslating into PLAs at the rate we thought they would," said Zoonat the BioEast '95 conference last week here. "We are studying thisproblem and industry should look at it as well."

Rathmann offered one reason why he thinks PLAs are on thedecline: the FDA's burdensome over-regulation and "over-caution"during Phase I and Phase II trials. "People are focusing on reviewtimes at the FDA when the real bottleneck is the first five or six yearsof clinical investigation," said Rathmann. "User fees address theproblem late in the game, in the last year and a half of the drugdevelopment process."

For example, he cited dosing and dose escalation studies as an areawhere FDA reviewers are increasingly insisting on time-consumingprocedures. "There's been a change toward a more conservativeposition on these early studies in the last year and a half and I thinkit's a result of fialuridine," he said. (Fialuridine was an experimentalnucleoside analog that unexpectedly killed five patients during aPhase II study in 1993.) He also said that FDA rules governingmanufacturing and process controls are antiquated.

FDA spokesman Donald McLearn said criticizing CBER forapproving one biologic with a staff of 776 people was "unfair andmisleading." In fact, only 200 people at CBER work in thetherapeutic biologics review division. The rest are divided among theblood products, vaccines, compliance, and ELA divisions. Accordingto FDA records, CBER as a whole took 1,730 "actions" in 1994,including 15 "major biologics approvals" (the agency countsvaccines, diagnostics, and new indication and dosage approvalsamong these) and 896 ELA and PLA supplement approvals. "Thenumber of biotech products approved is not going to go up everyyear unless the applications go up," McLearn told BioWorld.

Greg Simon, chief domestic policy advisor to Vice President AlGore, told BioWorld that criticisms of the FDA don't jibe with therecord review times being reported. "My feeling is, don't make theFDA the first target when most analysts agree that the biotechindustry's problems have been the difficulty of creating successfuldrugs, not the review process," he said. n

-- Lisa Piercey Washington Editor

(c) 1997 American Health Consultants. All rights reserved.

No Comments