12 letters negated via pilot; device letters down 65% for first half of fiscal 1999.

Dear Reader,

FDA's much-heralded pilot to help device makers avoid a warning letter by responding adequately to a 483 only has negated 12 warning letters so far.

Statistics from March 29 -- when the pilot began -- to early August also show that eight firms wound up with warning letters after not addressing 483 citations, said Lillian Gill, director of the Office of Compliance in FDA's Center for Devices. She said this means the inspections were still considered "violative," and rated "Official Action Indicated" (OAI).

In the 12 cases in which warning letters were avoided, device manufacturers still received "post- inspection notification letters" (PINLs), Gill told the annual meeting of the Regulatory Affairs Professionals Society (RAPS), held Oct. 5 in Washington. This means the inspection also was OAI, but "the issues were addressed" in the company's reply to the 483, so the manufacturer avoided a warning letter.

In an interview after her talk, Gill said "it's still too early to tell" how many cases there were in which FDA avoided sending manufacturers warning letters.

But for the first six months of fiscal 1999 -- Oct. 1, 1998, through March 31 -- the agency only issued 115 warning letters compared to 320 for the same period in fiscal 1998. Gill explained the 65% drop as follows:

"We haven't done as many inspections, but certainly, there was some anticipation that this pilot was coming out, so I do expect the number of warning letters to be less because there is an alternative mechanism to a company responding."

If FDA finds the warning letter-avoidance system useful, it may become agency policy, at least for makers of human and animal drugs and biologics (with the possible exception of blood and plasma establishments).

Such was the case with pre-announced inspections, annotated 483s and letters from FDA saying a plant was in compliance. These reforms were tested with the device industry in 1996 and were adopted for drugs and biologics last November.

However, a member of the grass roots industry group that helped establish the device warning letter pilot criticized the exclusion of devices regulated by the Center for Biologics from the warning letter pilot.

Glenn Paul Freiberg, senior director of regulatory affairs, Gen-Probe, told RAPS that makers of devices regulated by CBER such as in vitro diagnostics (IVDs) and blood bank software -- should now be included in the warning letter pilot.

Freiberg said, however, that when the grass roots team got together in 1997 to lay the ground work for the pilot, FDA did not bring CBER officials to the table, nor did the agency -- or industry members -- request that biological devices be added.

Freiberg stated further that CBER-regulated devices should be removed from "Team Biologics" inspections. He argued that some members of the core inspection team -- which has increased from 12 to 20 FDAers since April 1998 -- expect IVDs, at least, to abide by drug GMPs.

Using label reconciliation as an example, Freiberg said "it's a good idea" for diagnostics to have ensure they have the correct quantity of labels for products, but noted that "this is not a requirement just a good idea." He argued that some biologics inspectors expect IVD makers to apply this drug GMP requirement.

Freiberg advocated that CDRH take over the regulation of all devices except those used to collect and process blood and plasma.

Dr. Lillian Yin, Ph.D., special adviser for device review in CBER, defended Team Biologics and said an agency-wide working group -- which comprises CDRH officials is trying to reconcile drug and device GMPs for devices.

This effort includes devising a document "clarifying applicability of stability and sterility requirements to CBER-regulated IVDs," and efforts to "lighten the inspection load" by identifying licensed biological devices where device standards alone could be applied.

Sincerely,

The Editors

The above-mentioned presentations on CBER-regulated devices plus Gill's presentation are $20 plus retrieval, Doc. 8121W.

The following symbols are used to flag certain warning letters containing alleged violations of specific FDA regulations and policies of current interest:

AE -- ADR, MDR reporting BiMo -- Sponsor/monitor, IRB, clinical investigator issues C-H -- Complaint handling CAPA -- Corrective and preventive action Comp/Soft -- Computer software validation, hazard analysis, component qualification Design -- Design control violations F-B -- Lack of fair balance in promotion NDA -- No drug application approved OL-Use -- Promoting a product outside its approved use OOS -- Out-of-specification results PMA -- Premarket Approval S-HACCP -- Violations of HACCP requirements for seafoods Val -- Validation Web -- Web-page promotion violation