A Medical Device Daily

Despite the availability of manufacturing expertise and advice, new and experienced firms alike run into trouble with FDA's 21 CFR 820 standards, such as corrective and preventive actions (CAPA) and validation for software and for changes to device design. Among the latest recipients of FDA warning letters is a firm that had not caught up with problems disclosed in a 2003 inspection and another that had to recall more than 2,500 infusion pumps due to faulty tubing.

The January inspection of the Lutz, Florida, plant operated by DBI America, makers of ultrasonic scalers, said that the firm's environmental controls for electrostatic discharge (ESD) were inadequate, with some circuit boards "observed touching each other and not being protected." Also, the type of wrist strap used by employees to prevent ESD was not periodically tested "to verify that it is functioning properly." The March 29 warning letter said that DBI lacked device history records and design control procedures, and no CAPA written procedures.

Employee training was the focus of two findings: DBI could not document employee training for welding procedures, or the minimum number of successful welds "before they are considered qualified." Employee training deficiencies were noted in the citations regarding ESD, specifically: no documents existed regarding ESD reduction procedures.

FDA cited the company for lack of documentation for inspection of incoming computer circuit boards and for supplier audits.

An April 24 warning letter to G&B Electronic Designs (Bordon, UK), makers of two ambulatory encephalographic recorders, said the company failed to validate automated welding processes and had no written procedures for installation and operational (IQ/OQ) qualification for equipment used to manufacture one of the recorders. The letter said the firm's response to this finding was inadequate because "you have confused process validation with equipment qualification" and the firm failed to offer a timetable for corrective action.

The November 2006 inspection cited failure to validate software for a variety of record keeping functions. FDA indicated that the firm offered to roll out a new system, which the agency said "may not be necessary," but that the company's corrective action for its use of Microsoft Word and Excel in these areas called for submission of validation procedures and a timetable for corrective action.

FDA also cited the company for failure to register the facility with the agency. The letter noted that "an FDA trip planner will be in touch with you shortly" to arrange follow-up inspection.

LifeCare Technologies (Tampa, Florida) fended off a warning letter for some months following the August 2006 inspection, but the company was unable to correct problems with its perinatal information network (PIN) software in time to dodge an April 2 warning letter. The lead citation was for failure to document "structural (white box) testing," including both independent code reviews and validation of the program compiler. FDA found the firm's proposed corrections inadequate. LifeCare could not document the rationale behind "significant changes" to PIN software dating to 1990, the agency said, and the company response "addressed design inputs" but not design changes.

The letter said the firm "received at least 16 complaints in 2006 concerning signal and/or data being lost at the central station or bedside monitor related to the PIN software, and failed to document the potential root cause of the problem." FDA said this under a citation for lack of procedures for CAPA and investigations into "the causes of non-conformities." The company's response failed to provide supporting documentation, thus deemed inadequate.

FDA also said that the company had not obtained premarket application approval for a version of the software that would access the Internet.

A March warning letter addressed to Sigma International (Medina, New York) ran to a hefty 15 pages, citing lapses in connection with its manufacture of patient-controlled analgesia/epidural analgesia infusion pumps. The company responded to the findings with three letters, in November and December 2006 and February 2007, but as the length of the warning letter and the inspection indicates the number of miscues was too great to overcome.

The letter cited failure to establish procedures for the documentation and validation of changes to the design of the firm's Spectra line of infusion pumps, the subject of a recall in June 2006. Sigma "recalled 2,455 units . . . due to several events where the pump tubing misloaded when installed by the end user."

Sigma redesigned the pump and rewrote a pair of software modules and, by FDA's account, restarted manufacturing operations prior to validating the changes. The agency alleged that the master engineering change notice for the individual changes in question was reviewed and approved by members of the firms' regulatory affairs and engineering staff "without ensuring that the appropriate validation/verification" for one of the software patches. Sigma is said to have distributed 257 of the redesigned units.

FDA cited Sigma separately for releasing units with the software patch despite the fact that those units did not have the related hardware.

The agency said Sigma had experienced an increase in the rate of battery failures and a tendency of the batteries to recharge to only 83% of their full capacity. Company records did not include documents to verify or validate corrective action, and the letter said that a complaint dated July 31, 2006, had not been entered into the CAPA system. FDA said, "this same deficiency was previously identified" in an April-May 2004 inspection.

Sigma returned a call to Medical Device Daily but declined to comment for the record.

The April 18 warning letter for TMED (Columbia, Tennessee), a maker of blood pressure cuffs said the company did poorly in January 2003 inspection for which no warning letter was issued. But FDA said in a warning letter, the result of a January 2007 audit, that "only one" of the items was corrected after that earlier inspection. Thus, the agency mandated that the company submit certifications by an outside inspector in November of 2007 and 2008.

The agency cited TMED's lack of requirements for analysis of quality reports and audits, service records and complaints, and for lack of a requirement for investigation of non-conformities.

The agency said that the company had no device history records (DHRs) for one lot of cuffs, and that DHRs for only six of 11 lots "contained the package labeling information, and none contained a facsimile of the graphics screen-printed on the blood pressure cuffs."

Perhaps the most damaging finding was that "the general manager, who identified himself as the most responsible individual at the firm, stated that he is unaware of any quality audits conducted since January 2003." TMED also reportedly had no procedures for medical device reports.