Medical Device Daily Washington Editor
The Feb. 26 warning letter to Guidewire Technologies (GT; Salem, New Hampshire) was fairly brief compared to many of the warning letters FDA puts out, covering only three citations. However, the agency fired off the warning letter within 15 days of the firm's response, which followed the end of the inspection by 20 days. This 35-day turnaround from the end of the inspection to the issuance of the warning letter is easily one of the fastest turn-around times for an FDA warning letter.
The agency also let it be known in the second paragraph of the warning letter that the firm's Feb. 11 response to the inspectional findings was not well received, and omitted any specific mentions of the corrections proposed by GT. The agency states broadly that GT's response “lacks documentation and evidence that you are implementing the corrective actions as stated,“ not a surprising finding given that the firm's president has serious disagreements with FDA's views on GT's operations. The inspection ran from Jan. 12 to Jan. 22.
The first citation was brief, and redaction rendered it cryptic. The citation, dealing with the firm's acceptance criteria for manufactured products, says that a test (the description of which was redacted) “is not conducted after each sterilization process for your sterile packed guidewires.“ FDA says that the firm's 510(k) submission for Teflon-coated guidewires requires that the label declare that the guidewires “will be [redacted]-free unless packaging is opened or damaged.“ The warning letter offers no further information on this finding.
GT's web site mentions that its guidewires are available with coatings of PTFE (polytetrafluoroethylene), which goes by the trade name of Teflon. An unspecified form of hydrophilic coating is also available, but the company's web site does not mention specific models.
Perhaps more problematic for the firm is that FDA alleges that GT did not validate the Teflon coating process. The warning letter also says that a piece of equipment that had been installed in the company's plant in 2008 “has no validation data available to demonstrate that this new process has not had an adverse effect on your manufacturing operations.“
The company's president, Douglas Curtis, told Medical Device Daily, “We're addressing all these issues,“ although he also said, “I do have some disagreement with“ the issues cited by FDA. He said the firm is working on further correspondence to address the issues and that the agency “will have my official reply at the end of next week.“
Regarding the Teflon coating, Curtis said he had showed and explained the firm's method of testing the coating, noting that the company “felt that process did not have to be validated.“ The issue came up during an inspection in 2008, and “during that investigation, I discussed how we can test [Teflon coating integrity],“ a method “which we then implemented,“ he said. Curtis added that the approach in question had satisfied the FDA investigator who handled an inspection in 2008 and that a different member of the agency's inspectorate handled this latest review.
“I don't have a problem with testing them,“ Curtis said, adding that GT is “currently doing an extensive testing of the adhesion“ of Teflon. However, he said that a full-blown process validation is not practical for the coating process.
Regarding the citation dealing with sterility, Curtis said, “they're referring to a 20-year-old 510(k) with a proposed label“ from that initial filing, “and the pyrogen-free [language] was removed when we went to our first label.“ He acknowledged that he did not notify FDA of the change, but added that he is “not aware of anything that requires notification of FDA for [such] changes from the proposed label to the final label.“
Curtis said that pyrogens were an area of huge concern at the time and that the absolute removal of pyrogens is a nearly unattainable state. “We've already tested them and they came back practically non-existent for pyrogens,“ Curtis said, adding that GT will test each load going forward, albeit “for informational purposes only.“
DePuy warns docs of ASR unit failures
The orthopedics sector has been haunted recently by more controversy than perhaps even the cardiovascular sector, and a recent report by DePuy Orthopaedics (Warsaw, Indiana), figures to increase scrutiny further of both the device industry as a whole and possibly the 510(k) program in particular.
DePuy recently informed physicians in a March 6 letter that data from Australia indicate that the ASR hip replacement system has exhibited a higher failure rate than anticipated in smaller patients when applied as part of a full hip replacement unit, necessitating revision surgery in numerous cases. The ASR is now off the Australian market, although the firm had announced earlier that it would pull the device altogether by the end of this year.
Much of the data on the device's problems suggests that the ASR is more sensitive to the surgeon's positioning of the implant than other such systems because of the dimensions of the ASR acetabular cup component, and wire service reports indicate that more than half the 300 U.S. patients who complained about the unit have had the unit removed and replaced. The news couldn't come at a worse time for the 510(k) program inasmuch as the acetabular cup component of ASR is said in wire service reports to have been cleared via a 510(k), rather than approved via a PMA. The company confirmed this, although the clinical trials database at clinicaltrials.gov mentions a trial for the ASR XL unit.
Mindy Tinsley, director of worldwide communications for DePuy, told MDD in an e-mail that the firm's data, including post-market data, indicate that the ASR “was performing in line with other monoblock systems when the full scope of data was taken into account.“ However, she confirmed that recent data show a “higher than expected revision rate for the DePuy ASR XL“ metal-on-metal components and the ASR resurfacing unit “when used with smaller head sizes.“ However, she said that the decision to terminate marketing of the XL and the ASR cup unit was “unrelated“ to the reports of failure and was prompted by falling demand.
Medtronic DBS data misses efficacy mark
Medtronic Neuromodulation (MN; Minneapolis) faces an advisory committee hearing tomorrow for its deep-brain stimulator for treatment of epilepsy, but documents released in advance of the hearing suggest that the clinical trial data may hamper the firm's effort to gain approval for the indication. According to documents released yesterday, the device failed to meet the clinical efficacy endpoint, although by very little, but MN apparently intends to ask the panel to vote on the use of the Activa DBS for epilepsy rather than the Kinetra, the unit for which the data in question were collected.
One of the factors that will surely work in the company's favor, however, is that the current state-of-the-art for epilepsy treatment is ineffective, making this a poorly met need at best. Cyberonics (Houston) has an approved electrostimulation device for epilepsy in the form of its vagus nerve stimulator, but wire service reports indicate the device is not selling well, and pharmacological therapy is seen as largely ineffective at present.
Mark McCarty, 703-268-5690