Medical Device Daily Washington Editor

The progress of medicine is nothing if not uneven, and the recent public safety notification called by FDA regarding recombinant human bone morphogenic protein (rhBMP) highlights the hazards posed by novel technologies.

The July 1 notice states that FDA "has received at least 38 reports of complications during the last four years" in cervical spine applications of the product. Among the complications are swelling of neck and the throat tissues, which the agency says "resulted in compression of the airway and/or neurological structures in the neck." Severe cases of difficulty in swallowing have also been reported.

FDA says that the data indicate that "most complications occurred between two and 14 days post-operatively, with only a few events occurring prior to day two." Among the interventions necessitated were tracheotomy, administration of anti-inflammatory medication and intubation. However, the notice states that the effect in some cases necessitated "second surgeries to drain the surgical site."

The product is not approved for use in the cervical spine, but is part of a PMA for lumbar spine use as part of the Infuse line of products made by Medtronic (Minneapolis), as well as for an ingredient in a putty made by Stryker (Kalamazoo, Michigan) the OP-1 implant and OP-1 putty.

Medtronic recently got the nod from FDA to sell the InFuse kit for uses in other spinal fusion and for use in fractures of the tibia, one of the two main bones of the lower leg. FDA also gave the nod to the product for use in dental bone regeneration applications.

Chuck Grothaus, senior public relations manager at Medtronic's corporate offices, told Medical Device Daily in an e-mail statement that a similar problem with rhBMP cropped up in 2004, but that Medtronic added a warning to the product's label advising physicians about the risk of such complications. Regarding a clinical trial the company is conducting for rhBMP in conjunction with a cervical spacer and an anterior cervical plate, Grothaus said that the public health notice "does not have an impact with the progression of ongoing IDE clinical trials."

"FDA has not asked us to take any further action that would affect or interfere with the progression of the ongoing IDE clinical trials," Grothaus said. He said the firm has finished site enrollment but that trials are still open for additional patient enrollment.

A Stryker spokesman told MDD that the firm does not comment on FDA advisories.

Synapse gets warning for bi-mo lapses

Most device firms know full well the requirements of clinical trial conduct, but still FDA has to hang the periodic warning letter on sponsors who fail to closely track how those trials are documented.

Count Synapse Biomedical (Oberlin, Ohio) as one of those, as indicated by the June 20 warning letter the agency sent off to the maker of the NeuRX DPS, a device designed to restore pulmonary function in paralyzed patients. The device stimulates the function of the diaphragm so as to free them from a life on conventional ventilators 24 hours a day. FDA recently gave the company a green light to go to market with the NeuRx.

The warning letter, which cited the company's sponsorship and review of a clinical trial, was heavily redacted for the name of the device, but the web site lists the company as the sponsor of only two trials, both involving the NeuRx. One is for patients with spinal injuries, the same indication as was recently approved, and the other for patients with amyotrophic lateral sclerosis, also known as Lou Gehrig's disease.

The letter said that Synapse expanded the trial "to four additional clinical sites without prior FDA approval." FDA deemed the company's response to this finding on the 483 inadequate due to lack of a corrective action plan to prevent recurrence, and FDA requested a copy of any such procedures.

FDA also cited the firm's standard operating procedures (SOPs) for study monitoring, noting that Synapse "could not provide documentation of monitoring for the [redacted] involving 16 subjects after you acquired sponsorship of the IDE" on a date that was also redacted.

One study site lacked records for exams such as electrocardiograms, chest X-rays and neurological evaluations. Two other sites also fed this citation, with one apparently exhibiting discrepancies between case report forms and another lacking documentation regarding the completion of procedures and patient check-ups. FDA asked the firm for expected dates for completion of training of study site personnel on record-keeping requirements, and recommended that Synapse "add [reporting of] protocol deviations to your SOPs."

In an e-mailed statement, Synapse President/CEO Anthony Ignagni told MDD that the company "was aware of the four issues raised in the FDA warning letter," thanks to "an audit that took place in March 2008." He also said that the company had "already initiated corrective action and responded to the FDA prior to the issuance of the warning letter."

Ignagni also pointed out that the agency nonetheless issued the firm a PMA for the NeuRx, and said "we anticipate a speedy resolution to the issues raised in the warning letter."

CMS adds to cancer reference library

CMS reported yesterday that it has added Clinical Pharmacology, a publication of the Gold Standard, a publisher recently purchased by Elsevier (Amsterdam, the Netherlands), in adding to the data it uses in determining which chemotherapy drugs are covered under Medicare Part B.

Acting CMS administrator Kerry Weems said the decision "completes our review of the compendia requests received earlier this year, and we remain committed to this compendia process that allows for updating the Medicare compendia in a transparent way." The other two publications in this group are Drugs & Biologics Compendium, published by the National Comprehensive Cancer Network (Fort Washington, Pennsylvania), and Micromedex DrugDex, a publication of Thomson Reuters (New York).