CDER eyes end of repeat warning letters; CDRH to spot-audit Class I makers.

FDA wants to get back to the policy of firms getting only one warning letter, not repeat letters, before the agency swoops in with stiffer enforcement actions.

Joseph Famulare, director of CDER's Division of Manufacturing and Product Quality, told the annual Regulatory Affairs Professionals Society (RAPS) meeting last month that FDA found itself in a practice in recent years of issuing firms multiple warning letters instead of taking action - i.e., seizures or injunctions - after one warning letter that does not get resolved.

"We want to look at that," he said. "It's always been our intention to send one warning letter but as we look over the last few years, we sometimes see more than one or more than one site. It makes you to start looking at the corporate entity."

He identified no examples, but perhaps the most notable case of a firm that received multiple warning letters, only to be found in continuous violation of GMPs, was Schering-Plough. But FDA has issued no consent decree as yet.

Famulare said the agency's move to "systems-based" inspections, wherein FDA examines subsystems of a firm's overall quality assurance program, is designed to get after corporate management responsibility.

He said FDA's drug field committee has approved the expansion of the pilot program for systems audits, which began earlier this year. This means all human drug manufacturers are subject to this new style of audit come January.

Under the new compliance program, FDA can declare a company's QA to be "out of control" if one system is not in compliance.

However, Famulare said there is no evidence of a trend toward the use of consent decrees and seeking disgorgement of profits, as was the case with Abbott Diagnostics and Wyeth-Ayerst's vaccine business.

He said the agency wants industry to comply so it is ramping up the release of several new guidance documents and rules.

For example, Famulare announced the work in reviewing comments for the draft GMP rewrite - issued in May 1996 - "is 80 or 90% complete. The last 20% represents a good body of the work to go through to prepare a Federal Register notice." In addition, the Center is working to revise medical gas GMPs, eyeing a proposal in "the next few months."

However, Famulare gave no time frame on when the drug or medical gas GMPs would be published.

He also said CDER will finalize the 1998 out-of-specifications results guidance, issue a guidance on cut labels and release a draft update of the 1987 aseptic processing guide - a document that has been expected for several years.

Meanwhile, FDA's Center for Devices has directed field districts to begin surveillance inspections of a random sampling of Class I device makers to see how they are complying with GMPs and Quality Systems rules. See next page...

CDRH Director David Feigal, M.D., told RAPS the sample will be based on 4,000 manufacturers "whom we do not normally visit."

He explained that these will not be quality systems audits, but described them as "short form inspections" that will involve no more than one day of an inspector's time.

"We have not inspected this category for five years, but have seen a cascading upward of recalls due to Class I devices," Feigal said. Class I device makers also are exempt from several facets of GMPs, such as design controls.

In an interview, he used as an example the now-defunct company Clinipad, which in March 2000 recalled millions of sterile pads because of the presence of Pseudomonas aeruginosa and Stenotrophomonas maltophilia. The Class I pads were incorporated in many device kits used in hospitals and blood banks. Thus, about 100 manufacturers were snared in the recall.

The products were tainted due to unsanitary water used in their preparation, sources said. The recall included products labeled sterile including povidone iodine, tincture of iodine and alcohol pads.

Feigal said the field assignment is in effect for this fiscal year (which ends next Sept. 30). Once complete, the agency will examine trends from 483s and EIRs and see where Class I device makers are having problems complying with GMPs.