By MARK McCARTY
Medical Device Daily Washington Editor
St. Jude Medical (St. Paul, Minnesota) took another hit for its Riata line of electrophysiology leads via an FDA announcement that all patients with these leads should be evaluated for lead externalization. The news dropped the firm's shares at the New York Stock Exchange, falling to as low as $36.59 from the day-high of $38. Recent reports had already driven down share prices with reports in July stating that a weak earnings environment is in the firm's future.
FDA's Aug. 16 announcement noted that the agency has mandated post-market section 522 studies for the Riata leads, but several other leads made by St. Jude are also on the 522 list, including some QuickFlex and QuickSite leads as well as Durata leads. The development comes on the heels of a study published last month by St. Jude indicating that conductors in the narrower 7Fr Riatas were less likely to externalize than the conductors in the fatter 8Fr leads (Medical Device Daily, July 17, 2012). The correlation between lead diameter and externalization was debated at the Heart Rhythm Society (Washington) annual meeting earlier this year (MDD, May 11, 2012), and FDA received no comment in its proposal to require PMAs for electrophysiology leads (MDD, July 9, 2012).
FDA's latest move was not well received by all. Edward Schloss, MD, director of electrophysiology at Christ Hospital (Cincinnati) told Medical Device Daily that the recommendation of imaging for all patients will put doctors and patients in a quandary. "To me the thing that will have the most impact on doctors is the X-ray" or other imaging recommendation, Schloss said, adding that this recommendation as a screening mechanism for lead externalization "goes outside what has been done in clinical trials."
Schloss said the recommendation "is going to create as many questions as answers." He explained that for a doctor, "the first question is when, how often, and what to do with the results." Schloss said he understood "why FDA would want this," but he argued, "to put a broad recommendation out to the [patient and physician] community" is going to foster a lot of uncertainty. He said there have been some specialty society discussions regarding the Riata predicament, but added, "there really is not a consensus" that broad-based imaging across the affected population "is appropriate," although Schloss acknowledged that some electrophysiologists favor the idea.
A common medical school recommendation, according to Schloss, arises in this kind of situation and addresses the dilemma precisely. "Never do a test unless the test is going to influence your management afterward," he said.
MDD asked how a patient might react or overreact to the news. "Based on my understanding, a functioning lead that's externalized should be followed closely, but not removed prophylactically," Schloss said, adding that he believes this is a commonly held view among electrophysiologists. Should a patient become anxious and ask to have the lead removed even when removal presents a greater hazard, he said, "if a patient asks for something to be done, but it's not medically advisable, it's the doctors job to advise the patient."
St. Jude said in an Aug. 16 statement that it "understand[s] the FDA's decision to recommend fluoroscopic or X-ray screening of all patients with a Riata lead," making note of the July announcement regarding the study the firm is already conducting. That study, St. Jude said, will run "over a minimum of the next two years," although the FDA 522 order requires three years. It was not clear from the St. Jude statement whether that study could be used to fulfill the 522 order.
St. Jude acknowledged that an externalized conductor "may present complex patient management considerations for physicians," but remarked that in published studies, "the majority of leads with externalized conductors have continued to function properly."
Asept Pak cited for IQ, OQ deviations
Two of the less commonplace citations found in FDA warning letters these days are those dealing with installation and operation qualification, but Asept Pak (Malone, New York) was cited for both in the firm's compounding of wound irrigation products and blow-seal-fill packaging of the products. The agency also found fault with the company's handling of an unconfirmed analysis of contamination of a batch of irrigation solution, and the warning letter closes by noting that Asept told the FDA investigator that it has "stopped manufacturing and distributing drug products."
The Aug. 7 warning letter stated that Asept had not documented the IQ and OQ work on compounding tanks prior to "executing process and product specific performance qualifications." FDA noted also that Asept was using "various compounding tanks" to produce USP-grade sterile sodium chloride and sterile water, adding that the validation for this product was performed on only one tank.
The warning letter pointed out that two of the tanks used air sparging to blend the components of the solution while the third employed an agitator. However, the agency also remarked that the three tanks are all of different volumes.
According to FDA, Asept did not "define and document" an approach to monitoring in-process controls for the blow-fill-seal process. Among the specifics cited here are process monitoring for the resin hopper, the molds used to form the containers, and six other system components, but the warning letter added that documentation for in-process monitoring also omitted controls for fill volume accuracy.
FDA said that Asept did not "initiate, conduct, and document any investigation" into a batch of sterile sodium chloride that tested positive for a species of bacillus. FDA says that a contract lab tested the batch, produced in August 2011 and released in March. FDA said that the contractor reported the contamination "on August 31, 2012," but the date may be assumed to be a typo on FDA's part, especially given that the warning letter states that the batch was retested with a negative outcome on Sept. 30, 2011.
FDA added that a second lab tested a sample from this batch, which also came back with negative results, but the agency nonetheless cited the company for failure to investigate the incident. The warning letter mentions no response to the inspectional findings from the June 11-20 inspection, and the firm did not respond to contacts for comment.
Mark McCarty, 703-268-5690
Published August 17, 2012