Medical Device Daily Washington Editor

FDA has issued a Federal Register notice that it has determined the regulatory review time for a pair of pacemakers manufactured by Medtronic (Minneapolis), and the outcome may be nothing of consequence other than a demonstration of how data can get lost in the bowels of U.S. government.

According to the notice, the U.S. Patent and Trademark Office "received a patent term restoration application for KDR 401 and 403 pacemakers," and PTO had to go back to FDA to settle a question about the effective date of the filing of the investigational device exemption (IDE). Medtronic had claimed that the effective IDE date was May 21, 1997, but FDA believes that the date is Feb. 16, 1996.

The firm and the agency agree that the PMA was approved on Jan. 30, 1998.

According to FDA, the total regulatory review period of 716 days was evenly split into a pair of 358-day slots, the first of which was for "the regulatory review period," the second of which serving as the approval phase.

The applicant is Stephen Duggan of Rosemont, Minnesota, who filed the initial patent in 1980 on behalf of Medtronic. PTO rejected the application on several occasions over the following four years, but finally approved the patent in 1990.

The notice states that "this applicant seeks 358 days of patent term extension" and urges "anyone with knowledge that these dates as published are incorrect" to contact the agency by July 24. Any parties who wish to contest whether Medtronic "acted with due diligence" in filing the petition for extension have until Nov. 21 to make such a case to the agency.

Tracy McNulty, a Medtronic spokesperson, told Medical Device Daily that Medtronic "applied for this patent term extension in March 1998 and has not filed anything subsequent in this patent matter."

She said there is "no impact to the patent term extension" caused by FDA's declaration of the effective IDE date. PTO was purportedly required to rule on the extension application within 60 days, and McNulty said that the company was surprised to see the Federal Register notice.

CuraScript gets warning for EtO sterilization

Among the warning letters posted at the FDA web site this week was one to CuraScript (Orlando, Florida), citing the specialty pharmacy/redistributor for eight deviations from good manufacturing practices, including failure to document the rationale for the use of ethylene oxide (EtO) sterilization in the manufacture of two lots of biopsy kits despite indications that containers of lidocaine in the kits might be compromised by EtO.

The supplier of the 1% and 2% lidocaine packets was said to have informed CuraScript of the situation, but CuraScript did not "document an appropriate justification" for proceeding with the sterilization of these two lots. FDA stated that the company's response to this finding was inadequate because "you have not established or implemented a procedure to ensure that all purchased products conform to requirements."

The letter stated that CuraScript did not inform FDA of a Feb. 15 removal from distribution of an unspecified number of biopsy kits due to reports of "excessive particulate matter" in 1% lidocaine packets.

FDA said that a contract sterilizer "did not follow the parameters established by your previous sterilization validation" because the contractor made changes to preconditioning temperature and humidity settings outside the parameters used during validation.

The warning alleged that CuraScript shipped an unspecified number of units of the affected product without taking the matter up with the contract sterilizer and without "determining the effects these changes might have on your EtO convenience kits." The response to this finding failed FDA's test due to lack of documentation that the change has been validated.

FDA acknowledged two responses by CuraScript's VP for custom medical products, Perry Phillips, but said his response to the first citation was inadequate because not including data indicating that testing for the lidocaine products indicated stability, partly because the data did not show that the method "is able to separate lidocaine and its respective degradant products."

A letter to Gustav Eles, DO, whose address was given as Allegheny General Hospital (Pittsburgh), cited the physician's participation in a clinical study (the study name, device and sponsor all redacted). FDA said that Eles had enrolled four subjects whose study data indicated ineligibility for procedures that were either conducted too far in advance of enrollment or too close to the enrollment date. Another subject was enrolled after a blood pressure check indicated a pressure of 204/87 in a March 8, 2006, check-up, "the same date as the study procedure" despite that hypertension was an exclusion criterion.

FDA's May 9 warning letter to Tosoh AIA (Toyama City, Japan), maker of assays for prostate-specific antigen, stated that samples containing monoclonal antibodies were stored at temperatures and humidities outside the range called for in a change to the assay design. The agency stated that the company's documents "suggested that the humidity was neither monitored nor recorded" and that Tosoh "failed to document storage details such as initial placement and any movement and/or the identification of the refrigerators in which the samples were stored."

The letter said the response to this finding failed to verify that "design outputs met the desired inputs" in terms of storage conditions and that the relevant document forms were not backed with data that "demonstrated that measurable design outputs were adequately defined to complete design validation activities."

The agency said the company's "electronic data did not correlate with the paper records" and that Tosoh "did not establish an electronic data back-up procedure."

The December 2006 inspection also disclosed that some data were copied between systems via a floppy disk, indicating that "no limited access or data protection had been established." The firm's response was shot down because "you failed to encrypt and/or physically secure your back-up data system."

FDA also cited the company for lack of username and password requirements and a lack of audit trails for software changes.

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