Medical Device Daily Washington Editor

The recent news of the shutdown of a reactor in the Netherlands that was producing molybdenum-99, a precursor agent for the anticarcinogenic technetium-99 (Medical Device Daily, Sept. 17, 2008) jangled a few nerves among radiation oncologists, especially given a previous decision on the part of Canadian authorities to end development of a new reactor for this application. This medical radioisotope is now back in the news with the release of a warning letter to Covidien (Mansfield, Massachusetts) addressing the company's processing of molybdenum-99 into technetium-99.

The Aug. 12 warning letter, which FDA posted early last week, addressed a March inspection of the firm's medical radioisotope plant in Maryland Heights, Missouri. The lead citation was for failure of the company's release limits for production of molybdenum-99 to "assure that the specification would be met." Molybdenum is a precursor material for technetium-99, which is used for treatment of a variety of cancers.

The agency said that the company's response to this finding indicated that Covidien had opted to deal with the related requirement by using a standard test method to predict the ratio of molybdenum to technetium, but FDA inquired as to "why you have chosen to set the limit in this manner versus setting a maximum limit that cannot be exceeded."

The letter cited Covidien for lack of established controls for "backwashing, column assembly and column activation ... to assure that the molybdenum adsorbs and remains adsorbed to the column," a failure of which was said to open the door to "molybdenum breakthrough effect." The agency said that the company's generator "is not a new product or process," but pressed Covidien to explain the source of "new unexplained variability in component quality and/or the manufacturing process," to which FDA chalked up a "recent increased number of molybdenum breakthrough complaints." The letter also stated that at the time of the inspection, Covidien had not studied "among other things, the washing process and particle size as well as how they impact product quality and function."

The company's responses apparently included reference to an investigation into the adsorption of molybdenum "onto the column," but FDA did not indicate the start date or projected duration of that investigation.

The warning letter also stated that the company's quality control unit missed on several points, including the molybdenum adsorption and the validation of "all key process variables." FDA said that while Covidien commenced with the related investigation in 2007, follow-up "did not occur until our representatives inspected your facility in March" and that the quality control unit had previously "failed to prevent the distribution of defective products." The agency also indicated that similar problems had shown up "in other product areas during previous inspections."

At press time, Covidien had not responded to calls for comment.

Pedicle screw maker hit with warning

Allez Spine (Irvine, California) also was the recipient of an August warning letter that surfaced at the FDA web site only last week. FDA cited the maker of pedicle screws for a number of citations indicating a lax quality control system, but the warning letter also indicated that Allez did not report to FDA several instances in which a failure of pedicle screws to fixate to the bone.

According to the warning letter, three complaints indicated that "your device failed to seat properly during initial implantation" and "the devices were therefore immediately explanted." FDA indicated that the company's investigation into the matter unearthed "evidence of cross threading and other distortions of the components in the returned devices," and the warning letter argued that these should have been forwarded as medical device reports (MDRs) because of the potential "to cause or contribute to a death or serious injury."

The company's response to this finding was deemed inadequate because "your files do not provide adequate documentation to support the reasonableness" of the initial conclusion that the events were not reportable. The company was said to have later reviewed and reported the events based on "unspecified information."

FDA also said that Allez had no PMA or 510(k) for the company's Laguna polyaxial pedical screw system, a citation apparently based on several changes made to the device. These included a change from "a two-piece press-fit locking nut to a two-piece welded locking nut" and "several revisions of to the thread profile of the locking nut." The agency made the case that such changes "raise the risk of decreased biomechanical performance, which could in turn lead to adverse events."

Among the more routine citations covering good manufacturing processes was a failure to validate changes to the design of an unspecified item "from a welded two-piece locknut to a one-piece locknut." At press time, Allez had not responded to a call for comment.

FDA hits firm with detention

The Aug. 20 warning letter addressed to Suarez Corp/dba Biotech Research (Canton, Ohio) led off by notifying the company that it had neither PMAs or 510(k)s for several of the firm's offerings, which includes the PainNOT heating pad. The letter also said that the company failed to file MDRs for two instances of burns associated with the use of the PainNOT. In one case, a user received third-degree burns "because he was not warned that the device used infrared heat," and in the other instance, a user received second-degree burns on his upper back, for which he went to an emergency room for treatment.

The letter notes seven other instances in which the company failed to file MDRs, and followed with a citation for lack of procedures for filing MDRs with the agency. FDA noted that Suarez was in the process of developing such procedures, but that they were incomplete as of the date of the warning letter.

The company apparently sent letters to owners of the Foot Choice infrared heat massager to urge the customers to "check the skin in contact with the heated area ... frequently to reduce the risk of burns or blistering," in 2006. FDA noted that the company failed to inform the agency of this action.

FDA also cited the company's PainNOT patch as a new drug for which the company had no new drug application, and informed the company – which is said to import at least most of its products from its overseas locations – that its products would be detained. At press time, the company had not responded to calls for comment.