Medical Device Daily Washington Editor
Corrective and preventive action (CAPA) citations have peppered warning letters for at least a decade, and the June 26 warning letter to St. Jude Medical (St. Paul, Minnesota) addressing a March-April inspection of the company's neuromodulation division in Plano, Texas, offered no exception. FDA shot down the firm's responses to each of the warning letter's five detailed findings, two of which dealt with CAPAs in connection with the MTS (multiprogram trial stimulator) stimulators and the Eon implantable pulse generators made at the Plano plant formerly was operated by Advanced Neuromodulation Systems (ANS) before St. Jude bought the firm in 2005 (the ANS unit is still referred to as such in the warning letter).
Among the findings addressed by FDA was one that dealt with a removal last year of MTS units due to one hardware and two software problems, including a May 15, 2007, marketing update which "discussed unequal electric field strengths between the two sides of the charging antenna." Another CAPA was undertaken in response to "low antenna voltages of the returned chargers and possible ... explants if the replacement charger does not address the patient's concern." However, FDA did not indicate whether any explants in fact took place.
The agency acknowledged the company's proposed fixes to deal with this set of problems, but nonetheless said the actions "did not address the gaps in your company's design and production controls that caused the quality problems in the first place."
The warning letter also alleged that ANS had not "completed, implemented or verified the effectiveness of at least 18" CAPAs for the MTS and Eon line of stimulators at the time of the inspection, which took place between March 5 and April 6. One of those CAPAs assigned "design" as the root cause of an uptick in complaints that were associated with a software upgrade to an unspecified number of MTS units "to correct a timing problem causing system error codes ... and/or a loss of stimulation." This or other design issues, which were not described in any detail, were also assigned as the cause of three other CAPAs, one of which dealt with a defect in a printed circuit board. Again, details were lacking.
FDA indicated it was dissatisfied with the company's response to this set of findings, indicating that while the two CAPAs described above had been completed, the remaining two were outstanding as of the date of the warning letter. FDA said ANS "must perform extended field monitoring" and other quality data analyses "to prove that the design changes or production changes ... will in fact correct the quality problems and will not introduce adverse problems."
According to the warning letter, St. Jude had agreed to provide quarterly updates regarding the company's progress in amending its quality system. A company spokesperson returned a call to Medical Device Daily, but could not respond to specific questions other than to note that FDA's action has not led to a quarantine of the affected products. St. Jude's 8-K statement dated July 1 notes that "customer orders are not expected to be impacted" and that the firm "believes that FDA's concerns can be resolved without a material impact on the company's financial results."
Among the other citations are those dealing with design validation, finished device acceptance activities and complaint handling procedures.
Design reviews getting closer scrutiny
FDA's 11-point warning letter to auditory device maker Puretone (Rochester, UK) dealt with a variety of problems, including CAPA citation, and the agency concluded that the problems were serious enough to warrant detention of the company's devices pending a response to the warning letter and a possible re-inspection.
However, Puretone is the second company operating in the UK to receive a recent warning letter that cited the recipient for failure to include a disinterested party in reviews of device designs. Puretone's design review procedure was said to lack a requirement that an employee who has no direct responsibility for device designs be present during reviews of those designs. This issue also surfaced in a recent warning letter to Inditherm Medical (Rotherham, UK) (Medical Device Daily, July 14, 2009). Whether this constitutes a trend in terms of FDA's emphasis during inspections is not yet clear, but Puretone's proposed correction for this finding was deemed adequate.
The warning letter, which was extensively redacted, led with a citation for lack of a CAPA requirement for review of individual returned items, adding that the firm's procedures "do not address at what point the data analyses will result in corrective and preventive actions, but rather just the point at which the data must be investigated."
Much of the detail from this section of the warning letter was purged but FDA noted that as of December 2008, Puretone would henceforth analyze all units returned for credit to determine the problem. The firm's response was said to have lacked "a description and evidence of implementation of the new policy."
Device history records ran afoul of what appears to be poor bookkeeping on the part of Puretone. According to FDA, the company could not locate a device history record for a Sept. 1, 2008, shipment of tinnitus maskers because "the lot number listed on the invoice is not a valid lot number." FDA also states that the company's records another shipment of tinnitus maskers "includes serial numbers for only 23 units," although FDA saw fit to purge the number of units included in the shipment in question. Other tinnitus maskers were said to have been described in DHRs as "both passing and failing the final test" after a rework.
FDA, which listed a total of nine classes of problems with device history records – one of which included 12 documented instances – noted that Puretone did not respond to that finding. This was also the case for citations for labeling operations and returned product reworks.