Medical Device Daily Washington Editor

The July 30 warning letter to Medical Accessories (MA; Trenton, New Jersey) may be an example of the kinds of repeat offenders that will almost surely get less lenient treatment from the agency in the Margaret Hamburg era. FDA notes in the warning letter that a previous inspection disclosed at least two of the same problems, an assertion supported by the fact that MA received a previous warning letter in 2002.

The current inspection, which commenced April 27, disclosed that the maker of a variety of devices, including blood pressure cuffs and ultrasonic transducers, had no procedures for corrective and preventive actions (CAPAs). According to FDA, the firm told the FDA investigator that CAPAs had been conducted "in the past," but that MA kept "no records regarding any such actions." The agency noted that a similar finding was noted in a previous inspection.

The previous warning letter to MA, dated Feb. 4, 2002, did indeed note a problem with an absence of CAPA procedures, and the firm's proposed solution at the time, although not well detailed by FDA, was said to have addressed "problems found by the production operators," but failed to "address other sources of quality data such as quality audit reports, quality records, service records, complaints, and returned product."

In the second finding, FDA provided neither details nor a response on the part of the company for a citation stating that MA had no complaint-handling procedures. According to the warning letter, the company "handles all complaints verbally and does not maintain any written complaint files."

MA's acceptance procedures were said to have failed to require documentation of pressure tests performed on blood pressure cuffs to check for air leaks. This situation also led to a citation for lack of procedures for control of non-conforming product. According to the warning letter, any cuffs that flunked the pressure test were either discarded or repaired and tested again without documenting the action or the rationale for the rework. The agency states further that MA failed "to evaluate and document nonconformance to determine the need for an investigation and/or notification of the persons responsible for the nonconformance."

MA was cited for lack of device master records for several products and for lack of device history records for "tocotransducers manufactured in October 2008." The warning letter also noted that MA had no procedures for medical device reports, an issue the agency says "was discussed with you during a previous inspection." This finding, too, was noted in the warning letter from 2002.

FDA also noted that the company did not register the plant as the site of medical device manufacturing. The company's president, Janis Ziedonis, declined to comment for the record.

Medtronic gets extension for Talent

FDA reported last year that it had granted Medtronic (Minneapolis, Minnesota) a PMA for the Talent stent system for treatment of aneurysms of the abdominal portion of the aorta (Medical Device Daily, April 17, 2008) and per a request by the U.S. Patent and Trademark Office, has informed PTO that the amount of time PTO can award back to Medtronic for patent exclusivity is 1,183 days.

The calculation for this proposed extension is based on the commencement of the testing phase, pegged at April 11, 1997. Medtronic submitted the final PMA paperwork to FDA in October 2007, which gives the other boundary of the testing phase. However, regulations allow a firm to claw back only half the testing phase along with the entire approval phase, thus rendering the final figure of 1,183, which comes to roughly 3.24 years.

According to PTO, the claims for this patent include a hollow placement device and a guidewire, but the principal element consists of "a memory alloy element formed at least partly from pseudoelastic shape-memory alloy" made of a crystalline metal known as martensite. The martensite in the Talent is formulated so as to allow the stent to conform to the aorta at body temperatures, but to resume its manufactured geometry at lower temperatures.

Medtronic initially filed the patent claim in June 1995 and obtained a patent October 23, 2001, a stretch of more than six years. Assuming the patent gets the standard 20-year period of exclusivity and assuming PTO goes along with FDA's calculation of the relevant portion of the regulatory review period of 1,183 days, this patent will remain in force until January 2025.

Two offerings from NIH for licensing

The National Institutes of Health reported that it is offering two items for licensing that might interest anyone in the business of making vaccines or diagnostics dealing with infectious agents.

In the Sept. 4 edition of the Federal Register, NIH states that it has developed an attenuated chimerical virus that can be used to develop vaccines and therapeutic agents for tick-borne encephalitis virus (TBEV). NIH states that this condition occurs primarily in unspecified areas of Eastern Europe and Russia, infecting roughly 14,000 humans each year, but the 30% mortality rate is conspicuous. FDA has not yet approved any vaccine or therapeutic agent for TBEV.

NIH scientists came up with this chimerical replica of TBEV by leveraging a chimera developed for type 4 Dengue fever, using that development to attenuate two classes of surface proteins found on TBEV. The resulting product was tested in both mice and chimpanzees and can be used to develop a diagnostic, NIH states.

NIH is also offering for licensure two monoclonal antibodies for Bacillus anthracis, the pathogen responsible for anthrax. NIH scientists exposed chimpanzees several times to glutamic polymers similar to those found on the surfaces of the B. anthracis bacterium, and drew samples of the chimps' bone marrow to obtain the antibodies, both of which are said to have induced "full or nearly full protection" in mice at a dose of .3 milligrams. The notice does not state whether this was a single-dose regimen.

Interested parties should contact the NIH Office of Technology Transfer.

Mark McCarty, 703-268-5690;
mark.mccarty@ahcmedia.com