Carton Services slapped with 4-item 483 for failing to perform required equipment challenges.

Carton Services, Norris, TN, New Orleans District

Carton Services, Norris, TN, was hit with a four-item 483 because it failed to perform SOP-required equipment challenges, and for failing to follow protocol during validation studies.

FDA documents stated that Carton Services manufactures paperboard cartons, some of which contain pharmaceutical or dietary supplement labeling. The firm also performs some repackaging and relabeling of pharmaceutical and dietary supplement products.

During packaging, the EIR stated, the company performs challenges of some equipment, such as, testing the ability of an undisclosed machine to detect errors. Such challenges were not conducted at times documented in SOPs, New Orleans District Investigator Edward Maticka wrote, adding: "It was noted that the form used to document these challenges has only [undisclosed] line available to document challenges, even though multiple challenges may be required."

Next, the 483 stated during validation, protocol procedures "were not always followed and some failures to meet acceptance criteria were noted." The final report was approved even though some follow-up actions and re-validations were required, the report continued. Also, "no formal controls are in place to assure these follow-up actions will be completed," the EIR stated. Next, the final report concluded that an undisclosed machine speed had not been documented.

The EIR added that "the various protocol documents provided very little information on how equipment was to be set up and speeds at which equipment was to be run during the OQ [operational qualification] study." Also, Maticka wrote that he "asked what set-up instructions the operators had to work with at the time the OQ study was performed. Management stated they did not have anything in writing. This was considered objectionable."

The firm also was cited because performance qualification (PQ) batches were released by concurrent validation, although the company's procedures for process validation "describe no provisions or controls necessary for concurrent validation," the EIR noted. The report added that while some PQ documents were signed to indicate approval, not all data documents were signed, nor was there a formal report approving the validation package before release.

"I asked why they had distributed these lots," noted Maticka, "if PQ or process validation had not yet been completed on [undisclosed] lots. The firm indicated they were using concurrent validation." The FDAer then asked what kind of review had been performed prior to release of these lots to assure that all PQ acceptance criteria had been met. "David Ulbricht, corporate director of quality and technical services, stated he had reviewed the batch record data and signed off that they were acceptable for release."

However, there was no formal report describing the concurrent validation review performed, or justification for release of these lots prior to completion of process validation, the EIR stated.

The investigator added that while he did not object to their use of concurrent validation, "I did object to their lack of procedures and controls to assure any lots released during concurrent validation would meet all their PQ acceptance criteria."

Next, the company's final reports for IQ and OQ did not always discuss failures to follow protocols, the 483 noted. "The protocol for IQ does not clearly indicate how IQ is to be performed, but it does reference a number of appendices."

The IQ final report included each of these appendices, but several of them were not completed. Also, there were comments that these items still needed to be determined, the report continued. Also, "the final conclusion in the report is that all items set forth in the protocol have been found suitable. Failure to discuss the final report, and their failure to deter mine preventive maintenance requirements and lubricants allowed, was considered objectionable."

Maticka also noted in the EIR the failure to:

* Follow protocol for safety testing during OQ or describe failure to follow protocol in the final report;

* Have management sign and approve an investigation report before one of the concurrent validation lots was released;

* Ensuring that protocols had clear procedures for performing validation studies. FDA wrote that in some cases, protocols lacked clear acceptance criteria; and

* Have validation studies include a review of sops.

Carton Services did not respond to requests for comment before deadline.

Carton Services, Norris, TN, 6/11-12/02, Doc. 109747M, $5 plus retrieval.