Medical Device Daily Washington Editor

FDA recently opened an office in China, but the agency warned that the move was geared more toward consulting with that nation's State Food and Drug Administration than toward inspections of drug and device plants in the Orient.

All the same, three Asian device makers – two in China and one in Japan – were snared in the U.S. FDA's warning letter net, as indicated by last week's release by the agency. As might be expected, language issues cropped up inasmuch as some of the responses to the inspections were apparently provided in the native language of the firm.

An Aug. 18 warning letter to Fuji Systems (Tokyo) included boilerplate language that states that a failure to correct the problems could result in detention of the firm's catheters, but the relatively short warning letter, which included only three citations, suggests no such move is imminent.

FDA led with a two-part validation citation, the first of which was for failure to validate "the silicone tubing extrusion and vulcanization process." The warning letter also indicated a failure to establish pressure limits for a package sealing process.

The agency indicated that the firm's response to this finding was inadequate due to lack of a systemic review of other validations and states a preference for "a review of completed process validations." The letter also requests that further correspondence be "translated into English."

Corrective and preventive action (CAPA) issues also arose, with FDA asserting that Fuji's CAPA procedures did not require that such actions be checked to ensure they have not adversely affected devices. Again asking for documents translated into English, FDA states that Fuji's response "only confirms the need to revise your CAPA procedures," rather than offer a systemic fix. The warning letter also indicates that temperature gauges used in the package sealing process had not been calibrated.

Onbo Electronics (Shenzhen, China), maker of blood pressure monitors, provided FDA with two responses to the inspectional findings, and both were apparently written in English. This was of little help to the maker of blood pressure monitors and thermometers, given that the agency stamped out an Aug. 19 warning letter that described 11 citations.

The first citation noted that Onbo lacked procedures to identify the party responsible for tracking, trending and reporting complaints. The warning letter indicated that Onbo contracted this work to Microlife USA (Dunedin, Florida), but FDA found this arrangement dissatisfactory because Onbo failed to indicate how Microlife "is handling the complaint-handling process when the device history records are located at Onbo."

A water-cooling unit used in an injection-molding process drew two citations. FDA states that Onbo did not validate the use of the unit and deemed the company's response to this finding inadequate because the company "did not provide any corrective actions on the issue of changes and assess the effects of the changes on the validated process or systems." The letter also states that the cooling system was not qualified for installation, noting that the company's response indicates that Onbo did "not agree with the necessity of calibrating this equipment."

Onbo's position was apparently that the absolute temperature of the cooling water "is not a critical parameter to the molding process" because water temperatures affected only "the initial settings of the process parameters." This was said to have been backed by data on temperature ranges picked up later in the process, but FDA charged that the firm had no documentation that justified the selection of these in-process temperature ranges.

The warning letter states that Onbo could not justify a decision to not calibrate the water cooling unit, and that "there appears to be some confusion at your firm between installation qualification and calibration." The warning letter further states that the company did not provide "adequate justification for why the temperature of the water is not a critical parameter of the molding process validation."

Some warning letters gather plenty of moss on their way to the FDA web site, which was decidedly the case with the Jan. 31 warning letter to Teamedics (Shezhen, China). The maker of heating pads earned 11 citations in a sparsely detailed warning letter that led with a citation for failure to validate PVC (polyvinyl chloride) welders used to weld the edges of a heating pad.

The company also was cited for lack of design history files, a situation perhaps abetted by the practice of throwing away such files after two years, according to FDA. The agency went into no detail in citing Teamedics for environmental control issues, but the issues were apparently fairly simple. According to FDA, company officials explained to the FDA investigator that Teamedics "never made a complete assessment of what was needed in terms of environmental controls ... and so never determined how to implement or monitor environmental control issues."

Other citations include those for device history records in regard to the PVC welder situation noted above and failure to calibrate a voltage regulator used during welding operations for printed circuit boards.

Clinical investigator cited

Last week's published warning letters included one to Sarah Lisanby, MD, of Columbia University Medical Center (New York), citing the clinical investigator (CI) and study sponsor for failure to obtain the agency's approval prior to changing an investigational plan to boost the upper age limit for the unnamed clinical trial from 35 years of age to 75. However, Lisanby is said to have cleared the move with the study's institutional review board.

Lisanby is listed at as a principal investigator for eight trials employing transcranial magnetic fields for treatment of affective and behavioral disorders, but is not listed as a study sponsor on any of those.

FDA also states that Lisanby allowed CIs to participate in the trial without investigator agreements that included curricula vitae and financial disclosure information. Lisanby is said to have amended the appropriate procedures to cover these lapses, but FDA requested "a copy of this policy."

The agency cited Lisanby for several other lapses, and at the end of the warning letter asked her for "a complete list of all clinical trials which you have sponsored or participated in for the last five years." The agency states that it may "initiate disqualification proceedings against you."

A Medical Device Daily attempt to contact the physician for comment netted a response from Columbia, which stated in an e-mail, "We are in the process of responding to the FDA's letter. We have no further comment."