FDA PRE-APPROVAL INSPECTIONS RESULT IN 62% "TURNDOWN" RATE

FDA PRE-APPROVAL INSPECTIONS RESULT IN 62% "TURNDOWN" RATE from agency field staff recommendations, FDA Mid-Atlantic Region, Assistant Regional Food and Drug Director Joseph Phillips told a Jan. 31 Regulatory Affairs Professionals Society meeting. Of 384 inspections FDA completed from the beginning of the program in 1990 to the end of the year, he said, FDA is "recommending withholding approval on 237 of them." Phillips noted that "a little mathematics shows you that's a 62% [recommendation] turn- down rate. That's fairly high." The field staff recommended approval after the 147 other inspections. In total, FDA's Office of Compliance sent the district offices 644 requests for inspections during 1990. These requests involved NDAs, ANDAs and applications involving vendors and control labs. Of the 644 requests "the district directors are opting to inspect 384," Phillips said. The district offices decided that 225 of the applications did not require inspections. The FDA field staff recommended approval of 225 applications without resorting to pre-approval inspections based on "intelligence gathering." Counting the 147 approval recommendations following inspections, the field staff recommended a total of 372 applications for approval in 1990. Also speaking at the RAPS meeting, Office of Compliance Director Daniel Michels noted that the inspections are finding violations at an "unacceptably high rate." Several weeks ago, Michels told the National Association of Pharmaceutical Manufacturers' annual meeting that "serious" good manufacturing practice deficiencies have been discovered in about one of every three pre-approval inspections ("The Pink Sheet" Jan. 28, p. 5). Phillips reported that FDA is going to ask sponsors to submit a third copy of certain sections of NDAs or ANDAs to the agency to aid investigators during pre-approval inspections. The proposed rule requesting this additional submission was published in the Jan. 28 Federal Register. FDA is proposing in the notice that applicants of NDAs, ANDAs, and supplemental applications submit "an additional review copy of the chemistry and biopharmaceutics" and "an additional copy of the applicant's draft labeling." FDA also indicated that it may require in the chemistry, manufacturing and controls section "certain information concerning the batches used to perform bioavailability, bioequivalence, and stability tests, the master production record for a commercial lot, and the results of component testing" if that information is not "ordinarily" required. The extra copies will be used "during a pre-approval inspection to audit application commitments against actual manufacturing practices used by applicants." The notice points out that investigators usually do not have access to information in applications before or during an inspection unless they use the applicant's own copy of an NDA or ANDA. Comments on the proposed rule are due by March 29, 1991.