Corrections, actions drag between FDA, Stedim.

Stedim, S.A., Aubagne Cedex, France.

A four-day audit of Stedim in Aubagne, France, seemed to exemplify some of the alleged inconsistencies in FDA enforcement actions to-ward foreign facilities. The agency has been accused of conducting "quickie" inspections of foreign firms and long time lags in issuing warn-ing letters, compared with U.S. facilities.

The company makes a variety of intra-venous bags, connectors and adapters.

The September 1996 audit was scheduled to verify that corrective actions were taken follow-ing FDA's previous visit in July 1994, when the agency cited untested post-sterilization blister-pack seal strength, unevaluated manufacturing process changes, inadequate packaging process validation and a failure to requalify or validate sterilization equipment after implementing a new software system, the EIR stated.

FDA followed that audit with an untitled letter. However, time constraints prevented in-vestigator Janice King of the Atlanta District from verifying that all items in the letter were corrected, according to the report.

The records suggested some confusion in the agency about whether Stedim had received a warning or untitled letter in 1995. King referred to a warning letter repeatedly throughout the EIR, but crossed it out and changed it to "untitled" twice. There is no record of a 1995 Stedim warn-ing letter, at least one that was released to the public.

Warning letter follows non-response

Nevertheless, the 1996 inspection did yield a warning letter -- but more than two months after the inspection. Stedim had not even replied to the 483, according to the letter. In contrast, the EIR stated that management had promised a prompt response and corrective actions.

When King arrived, Stedim had just con-solidated manufacturing operations from two buildings into one expanded facility and was in the midst of related validation and qualification work, the records showed.

The firm had expanded its product line, adding the Bio-Pharm XL bag for the medical and biotech industries, and the Flexboy, designed to replace carboys in biopharmaceutical processing. A portion of this growth was attributed to U.S. sales. Stedim also has a plant in Pleasant Hill, CA, and a sales office in Tokyo, the EIR said.

The company continued to produce its earlier line, which consisted of a compounder adapter set, Biopharm media and recovery bags/ containers, total parenteral nutrition (TPN) bags, plasma bags, biotech bags and miscellaneous I.V. connection components, FDA records stated.

Despite the new products and facilities, the 1996 citations were largely a rerun of earlier 483s, records indicated. For instance:

* Failure to perform post-sterilization seal testing. The EIR termed this a repeat from July 1992. Fur-ther discussion showed that samples were tested, but King said the samples were not statistically supported, the EIR said.

* Unvalidated post-sterilization seal integrity. Stedim said a study had been performed but could not be located during the previous audit.

After evaluating the study in 1996, King pro-nounced it insufficient and cited it on the 483.

According to Francoise Gauduchon, de-scribed in the EIR as "responsible for quality control," Stedim was complying with the Norme Francaise regarding the effects of resterilization, but King said the firm could provide no docu-mented evidence that multiple resterilizations did not have an impact on either the product or the seals, the EIR said.

* Incomplete computer software validation. A com-pany response, dated July 3, 1995, claimed that validation of the software controlling the sterilizer was documented in 1994, but King determined that "very little had actually been performed," according to the EIR. The firm had no written software specifications, relying instead on an out-side firm's expertise, the report stated.

King also cited Stedim for not having a "for-mal detailed user-defined software requirements," a "formal software test plan," a "documented correla-tion between user requirements, software functional elements, and software verification activities to as-sure thorough test coverage" and documentation of specifications testing.

In addition, when a new microprocessor was installed, the firm had simply rewritten the old program in compatible language, the EIR said.

Reliance on contractor faulted

President and CEO Bernard LeMaitre questioned these observations, asserting that they addressed the contractor's responsibilities rather than Stedim's, but King insisted that it was not enough to rely on someone else's know-how, and the company needed to have software spec-ifications of its own.

The report stated that Stedim had made progress in other areas, including procedures to assure neatness (and avoid hair) in container storage bags, change controls, dating of steriliza-tion cycle checklists and documenting complaint investigations.

However, concerns about environmental monitoring in the clean room, cited in 1994, were not addressed in 1996 because the focus on other areas did not leave time, according to the EIR.

The partial corrections did not keep FDA from issuing a warning letter in November 1996, putting the company's products and spare parts at risk of import detention until the violations were corrected.

Stedim, S.A., Aubagne Cedex, France, 9/9-12/96, Doc. 108330M, $8 plus retrieval.