FDA cites Part 11 violations once again in 21-item 483 for device firm.

Carolina Liquid Chemistries Corp., Brea, CA, Irvine, CA, District

Carolina Liquid Chemistries Corp., Brea, CA, was cited in a recent inspection because its software and electronic records did not meet the requirements of FDA's electronic records regulations (21 CFR Part 11). In addition, the firm was cited because an adequate and effective quality system was not in place, and did not implement procedure for management review, resulting in a 21-item 483.

Conducting the audit of the medical device manufacturer were investigators Selene Torres and Vickie Anderson of the Irvine, CA, District Office. Only the 483 and the firm's written responses were available at press time.

According to the 483, "software used as part of production and the quality system has not been fully validated for its intended use according to an established protocol. Electronic records are used but they do not meet systems validation, system access limitation and audit trail requirements to ensure that they are trustworthy, reliable and generally equivalent to paper records."

Specifically, these systems were not properly validated:

* The web-based complaint-handling system;

* The receiving, shipping and inventory control software program;

* The bar code software used in production of finished device labeling; and

* The label printing software used in production of finished device labeling.

The company responded in a letter to FDA: "We are in the process of evaluating software validation SOPs with protocols and procedures for validation. Estimated time of completion is the second quarter of 2006."

Regarding the quality plan and system, the 483 stated that management did not implement and maintain a quality system. Further, the firm did not establish a quality plan. Also, "Quality Assurance SOP-4, page, 4.9, section for management meetings is incomplete," the 483 noted. Further, the company lacked documented management reviews from 2003 to 2005.

The firm stated that its internal audit procedure had been reviewed and approved by senior management.

Carolina Liquid replied: "Executive management has signed and approved a new quality system that will address all 21 CFR 820 guidelines." Part 820 are the GMP/Quality Systems regulations.

Next, "quality audits were not conducted at sufficient regular intervals, as prescribed by internal procedures to verify that the quality system is effective in fulfilling your quality system objectives," according to FDA documents.

Next, Carolina Liquid provided "no justification for not reporting a correction or removal action to FDA." For example, a product corrective action requesting replacement for lot #403302 for CK reagent did not meet stability claims and was not reported. Also unreported to the agency, the 483 noted, was a product corrective action dated Dec. 21, 2004, "concerning iron interference between Beckman's Iron reagent #467910 and Catch Homocysteine."

The company stated in response: "All four observations will be investigated as per SOP. All CAPAs [corrective and preventive actions] will contain a thorough examination with appropriate justification decisions based in reporting corrective actions to FDA ..."

In addition, complaint-handling procedures for complaints were not completed and implemented. For example, the complaint procedure in SOP-4, page 4.12, was incomplete in that it did not "define timeliness for processing complaints," or "require evaluation of complaints for medical device reporting (MDRs)," the 483 stated.

In a related violation, "records for complaints where no investigation was made do not always include the reason why." For example, the report noted, "there is no documented reason for no investigation of leaking cartridges, shipping errors, 32 complaints for HCY lot C050501 or 23 complaints for HCY lot HR103305."

Further, the report stated that "the documentation of approval of documents does not include the document approval date and the signature of the approving official. Electronic records are used but they do not meet systems validation and audit trail requirements ..." For example, device master records (DMRs) for in vitro diagnostics were not all signed and dated, and receiving procedure REC-001 with effective date December 2004 was not signed and approved prior to release.

The company responded that it had revised an SOP that provided a general calibration and certification schedule for all equipment used at Carolina Liquid.

Another observation in the FDA document was: "There is no clear agreement from the suppliers, contractors and consultants that they will notify you of changes in the product or service." Specifically, three of the four contracts reviewed for Class II in vitro diagnostic devices did not require the vendor to notify the firm for changes made to the product.

Also, records of acceptable suppliers, contractors and consultants were not maintained. Examples listed in the 483 included the contractor of the deionized water system and the software consultant.

Procedures to ensure that equipment was calibrated, checked and maintained also were not established, the document stated. For example, "refrigerators and freezers used to store raw materials and finished devices and the bulk material storage refrigerator was not calibrated as per the calibration sticker on the equipment."

The company was unavailable for comment.

Carolina Liquid Chemistries Corporation, Brea, CA, 10/26-11/8/05, Doc. 109840M, $6 plus retrieval.