The FDA’s device center has resumed a more normal pace of warning letter issuance in recent months, and the latest batch posted to the warning letter website features warning letters to one device maker in Europe and three firms in Asia. One U.S. firm, Steiner Biotechnology LLC, of Henderson, Nev., also received a warning, however, which is the second the company has received since June 2017.

The overall volume of FDA warning letters to device makers had ebbed considerably over the past few years even though the volume of inspectional forms 483 did not exhibit a proportionally similar track. Still, warnings to outside-U.S. (OUS) sites have recently been more conspicuous, and the newest posted batch of warnings includes several, including two threatening detention.

The Feb. 3, 2020, warning to Steiner stems from a June 2019 inspection taking up the company’s preclinical study of two orthopedic graft devices under an investigational device exemption (IDE). The FDA said Steiner had performed “repeated multiple surgeries on the same animals over time” despite that neither of the IDE protocols explicitly made provisions for repeat procedures. The agency said the company had also used a given animal in studies for both products in the absence of any provisions for such a practice in either protocol.

The company responded to the effect that this practice reduced the number of animals needed for these studies and that both studies employed the same grafting material, even though the site of application varied. The FDA’s objections were rooted in the prospect that these practices could increase the rate of bone fracture, particularly given the possibility of induced bilateral bone defect. This could induce “a high level of variability” in study data that may prove difficult to sort out, but the warning letter said this practice was not spelled out in the related protocols in any event.

Another deviation was the use of off-protocol anesthesia dosing for the animal models, a practice the agency said was purportedly supported by a veterinarian. The FDA said Steiner did not adequately respond to this finding and recommended the company “create or revise” a standard operating procedure to prevent recurrence of this violation.

Among the other violations cited in this latest warning to Steiner are a lack of quality assurance reviews of studies and record-keeping for specimen collection/retention. Steiner Laboratories received a June 21, 2017, warning citing the company for IDE studies, and while the company name is different, the addresses listed for each of these entities is identical. The 2017 warning cited the company for failure to obtain IRB approval of two IDE studies even though those studies were of significant risk devices.

The agency said that the devices used in these studies were “made up of two previously cleared devices,” and that the company was well founded in obtaining new 510(k)s for the study articles. According to the agency, the risk designation for the study articles had been communicated to Steiner on two occasions in 2011. Other citations for this warning are for “failure to maintain any protocols” for investigations and failure to maintain records for informed consent documents. Steiner did not respond to multiple contacts for comment.

Detention vowed for Hungarian firm

The Feb. 3 warning to Mandelay Kft, of Pest, Hungary, addressed an October 2019 inspection of Mandelay’s production of the Scientific Consciousness Interface Operation (SCIO) device, a bioresonance system. The warning cited Mandelay for failure to fully implement design controls for another product, the Quest 9 device, but the company’s response to the inspectional findings was inadequate.

Mandelay is said to have failed to address a citation for complaint-handling procedures in its response to the 483, but the company did respond to a 483 citation for activities designed to thwart electrostatic discharge (ESD). Despite three pieces of correspondence, including the provision of back-dated training records, the FDA said it was not clear whether any of the associated ESD training had been conducted. The agency said it may order a detention for any imports of the devices.

Cannula maker sees detention threat

The Sept. 20, 2019, warning to Dongguan Microview Medical Technology Co. Ltd., of Guangdong, China, threatens detention, given that the June 2019 inspection of the company’s production of cannulae did not include a validated process for ethylene oxide sterilization. Documents for the process in question failed to spell out the rationale for Dongguan’s selection of a process challenge device or the location of the placement of the biological indicator during sterilization validation work-ups. The FDA makes no mention of a response to the 483 for this or any other of the warning letter citations.

Another citation that drew the attention of the FDA field investigator was the presence of cases of raw materials in a storage room without acceptance status labels. FDA said also components stored in the floor of an ultrasonic cleaning room lacked labels indicating whether those components had been cleaned. The company is said to have lacked documentation in connection with a change of materials used in device packaging materials, and the agency said the net effect was to suggest adulteration.

Similarly, the March 2 warning letter to E-Care Technology Corp., of Chubei City, Taiwan, threatened detention of the company’s class II Swaive thermometers due to a number of quality control issues. Among these was a failure to consider several possible hazards in risk management reports, including the possibility that the manufacturing process may create “sharp edges” on the device, although the letter also cited storage conditions and inadequate packaging as other uncontrolled hazards.

E-Care had followed the October 2019 inspection with three pieces of correspondence, the last of which the FDA said was dated Feb. 20, but the agency said the company’s response to this citation came up short because of a lack of mitigations despite the company’s updated risk management plan. In addition, the FDA said, “it does not appear the firm performed any review or analysis to ensure this issue does not occur in the future.”

Among the other citations was one stating that the company’s medical device reporting procedures failed to define terms such as “become aware date” for complaints, and that E-Care did not have an electronic MDR account with the agency. E-Care had no better luck with its response to a finding that software validation reports did not document the results of testing for execution of mathematical operations or for information displayed “with 4 decimal digits and 5 icons.”

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