Five years of audits show ups and downs at Lifecore.

Lifecore Biomedical, Chaska, MN, Minneapolis District.

A combination drug-device inspection of Lifecore Biomedical in June 1996 focused on implementation of corrective actions promised following a February 1995 warning letter. FDA records show that in some cases, Lifecore had taken up to a year to put promised corrective actions in place after the previous audit.

The visit followed a patchwork of inspec-tions during the previous four years that showed fluctuations in the company's compliance record as it juggled the start-up of a new veterinary drug product, a move to a new location and response to FDA's observations.

An October 1992 audit yielded no 483, although Electronic Engineer Darin Busch noted some concerns about a delay in filing one MDR and incomplete information in another.

The agency returned just two months later to zero in on GMP compliance for Lifecore's endosseous implants. This EIR, signed by Investigator Jocelyn Muggli, hit complaint-handling procedures and more delays in filing MDRs. The company was then in the final stages of a move from Minneapolis to Chaska, MN.

EIR handwritten 

The Minneapolis district itself seemed to be in some type of transition. Muggli submitted the EIR in long-hand, which, she explained in the report, was necessitated by "a severe shortage of secretarial help."

In its written response, Lifecore responded that it had upgraded several SOPs. However, when Muggli returned in May 1994, she found that while the corrections were effective, Lifecore had taken about a year to implement them, the EIR stated. The accompanying 483 listed continued problems in complaint handling and slow filing of MDRs as late as June 1993.

A subsequent audit in July 1994, conducted by Investigator Jennifer Longie, looked at company preparations to start manufacturing a veterinary drug. Longie made some verbal suggestions that were noted in the EIR, but told management "their production and laboratory operations were operating in compliance with current drug GMPs."

In contrast, an audit extending from Aug. 29 through Oct. 17, 1994, yielded a warning letter that assailed the production of a drug product, Hy-50 Hylan hyaluronate sodium sterile injection. While the EIR for this inspection was not released, the warning letter and Lifecore's written responses indicated that FDA cited:

* Incomplete product validation.

* Concerns about adjustments to the manufacturing process.

* Lack of established bioburden and endotoxin levels for water systems.

* Use of an incorrect temperature for incubation.

* Lack of a second signature in maintenance logs to verify that work was completed.

Although a letter from FDA in February 1995 said the agency was satisfied with Lifecore's proposed corrections, further correspondence shows that the company still was providing an update on one remaining 483 observation in October 1995 -- a year after the inspection.

The June 1996 audit focused on verifying these changes. Investigator Sharon Thoma reported in the EIR that while Lifecore had cleared up 23 of the deficiencies, one remained outstanding. This one dealt with the second signature missing from maintenance logs, as cited in the warning letter.

Routine maintenance was properly signed, the EIR said, but unplanned maintenance was not. Management agreed and promised to correct this, according to the documents.

Besides checking on corrections to old issues, Thoma added some observations of her own:

* Failure of product/process validation to include "an evaluation of additional mixing times when adjustments are required." Management agreed, the report said, adding that the company planned to conduct this validation, a correction that would take about two months.

* USP growth promotion work sheets and a bioburden work sheet that lacked documentation of incubation temperatures. Management promised to revise the work sheets, the EIR said.

Thoma added a verbal observation involving a labeling issue. She noticed that labeling for Hy-50 Hylan lacked the required wording, "manufactured for," "manufactured by" or "manufacturer" followed by the Lifecore name and location. The omission resulted in misbranding, the EIR said.

When asked if the company could use up the remaining labeling stock for exported supplies, Thoma responded that she did not have "the authority to approve exportation of misbranded product," the EIR said.

Muggli performed the device portion of the June 1996 inspection. This time she found nothing amiss, the records show.

In a written response dated three days after the close of the inspection, Lifecore reaffirmed its promised actions to correct the drug-related observations. An update followed in September 1996, assuring FDA that the corrective actions were complete. The agency answered five days later that the corrections sounded adequate and would be verified at the next inspection.

Lifecore management declined comment on the inspections when contacted, citing turnover in the regulatory affairs staff since FDA's last visit.

Lifecore Biomedical, Chaska, MN, 10/6/92, 12/4, 7-10 & 17/92, 5/11-19/94, 7/14, 18, 20, 21/94, 6/11-14/96, Doc. 107995M, $39.50 plus handling.