Medical Device Daily Washington Editor

When several months pass between an inspection and the issuance of a warning letter, the tendency is to think that the company managed to trim the list of citations a little. One might also expect that after six months, a firm would at least have its paperwork in order.

A Jan. 28 warning addressed to Siemens Medical Solutions (SMS; Hoffman Estates, Illinois) suggests the opposite, with FDA noting that lack of documentation lay behind the agency’s determination that the company’s response was inadequate.

FDA said that SMS failed to follow its own procedures in validating software for the ECAT series of computerized tomography (CT) scanners, which resulted in “an error in the scan start time used in the decay correction algorithm.” The citation said that “the risk analysis for the hazard of linking PET/CT scans to the incorrect patient” had not been updated after three incidents that occurred after the previous update. The firm’s responses to these findings were deemed inadequate, for lack of documentation.

The warning letter listed a generic complaint about corrective and preventive action (CAPA) procedures, stating only that SMS’ procedures “inadequately identify quality data to be analyzed or the statistical methods to be used to analyze quality data.” The company’s response to this finding also fell short due to lack of documentation.

The question of linking scans to patients resurfaced in the fourth citation as a CAPA finding. FDA stated that the software that led to the four incidents in question had been patched, but apparently only for purchasers of PET/CT units purchased after July 2006. FDA also stated that the firm had not included “documented preventive action considerations” when filing Medical Device Reports for those incidents.

Regarding SMS’ response, FDA said that the response included no copies of the risk reassessment, and “since your firm has two different risk mitigations for the same problem, you should provide documentation showing both ... address the problem and are compliant with your current risk management procedures.” The agency said that Siemens did not provide copies of “the newly-created acceptance criteria for future revisions to the software.”

Siemens did not respond to calls for comment.

Clinical investigator a repeat violator

Heavily redacted warning letters leave a lot of questions unanswered, and the Jan. 30 letter addressed to Barry Katzen, MD, of the Baptist Cardiac and Vascular Institute (Miami, Florida) was one of these. The warning letter states that FDA audited the clinical investigator (CI) in October, but FDA makes no mention of responses to the inspection findings.

Katzen has been on the agency’s radar screen before.

According to the warning letter, a 2003 audit of Katzen’s activities disclosed similar problems, and FDA issued the CI an untitled letter in October that year.

“It appears the corrective actions you developed and implemented after the last FDA inspection are ineffective,” the agency said. The letter also stated that even though the sponsor may have been aware of the deviations from the protocol disclosed by the 2007 audit, “you are still held responsible for knowing and following the regulations pertinent to your activities as a clinical investigator.”

A search of the database at clinicaltrials.gov lists Katzen as an investigator in the recently completed VALOR study, which investigated stented grafts for thoracic aneurysms, sponsored by Medtronic Endovascular (Minneapolis). However, Katzen is listed as a CI in other studies as well.

The warning letter cited Katzen for failure to perform the required follow-up for four subjects in the unnamed study, and the relevant clinical details were also redacted. This citation was under a heading that alleged that Katzen failed to obtain, “in a non-emergency situation, prior approval by the sponsor of changes in or deviations from the investigational plan.” Katzen was also alleged to have failed to contact the study’s IRB as well as FDA regarding the changes.

The warning letter also cited Katzen for “discrepancies ... between diagnostic test reports, progress reports and case report forms.” However, the relevant information was again redacted.

Anne Smith, public relations manager at Baptist Cardiac and Vascular Center, told MDD only that “we’re in the process of responding to the warning letter.”

The Jan. 9 warning letter to Ansaar Rai, MD, of West Virginia University (Morgantown) addressed his participation in a trial for which the relevant data were redacted from the letter. FDA cited Rai for failure to obtain a dated consent form for one patient. Rai apparently responded with a dated consent form for the patient, but FDA indicated it wanted to see evidence of corrective action to “prevent this violation in the future.”

Rai was also cited for failure to report adverse events within the required timeframe, including one instance in which the patient experienced “a urinary tract infection with positive blood cultures” and another “suffered respiratory failure ... and expired.”

Rai was said to have filed the reports, but, again, FDA wanted to see corrective action to prevent such incidents in the future.

Rai told MDD,“I have already responded and from what I gather, my response is going to be satisfactory.”