Medical Device Daily Washington Editor

The May 18 warning letter to endoscope maker Karl Storz (Tuttlingen Germany) was populated with a dozen citations for deviations from the quality systems regulations, and although the company's responded within three weeks of the Feb. 2-5 inspection of the firm's plant in Schaffhausen, Switzerland, FDA notes that in nine instances, "the adequacy of [the firm's] response cannot be determined." The letter indicates that Storz had been snared partly by problems engendered by a vendor whose components were not up to snuff and partly by a lack of procedures to keep those vendors from shipping faulty parts.

FDA alleged that Storz's Schaffhausen plant had no standard operating procedure (SOP) for corrective and preventive action (CAPA) and says that Storz's Feb. 26 response to the inspection "did not properly address the documentation of orally initiated corrective measures." The warning letter asks for "proof of implementation" for several of the firm's proposed corrections, including one dealing with investigations into non-conforming components, and FDA suggested that the company rewrite its procedures to deal with "how to handle supplier-related non-conformities."

The purchased non-conforming items led to another citation, this one for lack of procedures for control of non-conforming products. This citation says that Storz had returned several items descriptions of which were redacted that failed finished-product testing, and the warning letter states that Storz could not document a corrective action in response. Again, FDA says it was unable to verify the adequacy of the company's response, said to consist of a revision of an SOP designed "to ensure that non-conforming components are properly investigated and reported by their respective suppliers."

On the same topic, FDA notes later in the warning that Storz did not follow its existing SOPs for non-conforming product in reference to "several failures of the [redacted] components of the [redacted] during finished product testing." The company's Feb. 26 response fell flat for this citation as well, with FDA asking for "proof of implementation" of an amended SOP.

The third citation hints at a need for site-specific compliance systems. In a citation under the heading of "failure to maintain adequate complaint files," FDA indicates that Storz's electronic complaint system does not deal with "potential complaints unique to the Schaffhausen operation."

The warning letter states that the firm's Feb. 26 response fails to address "the issue of keeping separate information for the two different facilities" in reference to the fact that Storz also manufactures the endoscopes at its Tuttlingen plant. Here again, FDA states that the adequacy of the firm's response "cannot be determined at this time."

Medical Device Daily was unable to find a statement addressing the warning letter at the Storz web site.

CI cited for informed consent lapses?

Failure to conform to informed consent requirements has long been a common citation and two recent warning letters to clinical investigators show that the trend is in no danger of fading anytime soon.

A July 1 warning letter to Thomas Jones, MD, of Seattle Children's Hospital (Seattle, Washington) dealt primarily with informed consent in an eight citation warning letter that led by stating that Jones enrolled patients in a trial without first obtaining final approval from an institutional review board (IRB). According to FDA, the IRB for the study, information on which was redacted from the warning letter, had only conditionally approved the study pending a report from a safety data monitoring board (DSMB) when Jones had implanted the device in four patients. The DSMB data were said to round out information regarding the risk of embolization, which was necessary for completion of a revised consent form.

FDA also states that Jones enrolled another 10 patients with the first version of the consent form after the IRB gave final consent. According to the warning letter, the hospital hired one full-time and one part-time assistant "to oversee these activities," but the agency asserted that it wants to see "documentation of corrective or preventative actions to ensure that subjects are not enrolled" prior to IRB approval and issuance of an updated consent form.

The warning letter states that Jones could not document that he sent annual progress reports to the sponsor. Jones' response to this inspectional finding, conveyed to FDA in an April 17 letter, was that he had sent the material electronically and that he had e-mail confirmations, but the agency deemed this response inadequate because "you did not provide copies of the e-mail confirmations."

At press time, Jones had not returned a call for comment.

Also appearing on the FDA warning letter page was a May 20 letter to Neil Feins, MD, of Children's Hospital Boston (Boston). Feins is listed in only two studies at clinicaltrials.gov, both of which are completed studies for minimally invasive closures of umbilical hernias sponsored by Q-Med Scandinavia (Princeton, New Jersey). The warning letter describes the physician as both a clinical investigator and a sponsor in the trial in question.

FDA states that Feins could produce no documentation "that a parent signed and dated an informed consent form (ICF) for one subject" in the unnamed trial and that Feins "did not use the [redacted] approved ICF for the subjects enrolled in this study." The warning letter indicates that the amendments to the consent form dealt with "cost to the subject" and included a privacy statement and a financial conflict-of-interest statement. The warning letter adds that the ICF "did not include a statement that the Food and Drug Administration may inspect the records in its confidentiality provision."

The agency adds that the unrevised consent form "contained positive statements of the investigational device's safety and effectiveness that are misleading with respect to foreseeable risks of the device." FDA purged the relevant details.

Fein is said to have "acknowledge[d] that you should have been using the [redacted] approved ICF and agree that in the future you will use the proper consent form," but FDA indicated that it was dissatisfied due to lack of "any new or revised policies and procedures that will ensure informed consent is obtained" per regulations.

At press time, Feins had not returned a call for comment.