Medical Device Daily Washington Editor

Orthopedic device makers know all about the intractability of problems associated with deterioration of knee cartilage even with hyaluronic acid products on the market, and it certainly does not hurt when regulatory authorities spell out their expectations for products intended for such uses. The European Medicines Agency (EMEA) posted a draft guidance yesterday to address the use of in vitro cultured autologous chondrocyte-containing products for this purpose.

EMEA notes that the guidance deals with aspects of this use of cell-based therapies that are not covered in a 2006 guidance that addresses human cell-based medicinal products, stating that the current guidance is intended to complement the 2006 document.

In a section addressing pharmacology, EMEA indicates that it is amenable to a proof-of-principal study conducted with any one of several three-dimensional cell culture models, including Pellet-culture models, and the agency adds that it is open to the use of small animal models for the first round of in vivo tests. However, the guidance urges sponsors to consider using goats, horses and sheep as models in the pivotal non-clinical study. Because the cells are autologous, EMEA will not necessarily insist on toxicology studies as such for animal models, adding that safety endpoints may be used to assess inflammatory response.

As for generating clinical data, the guidance remarks that the claims for the product could hinge on features such as whether the lesion was generated by trauma versus degenerative disease, and states that given these different etiologies, "separate safety and efficacy studies would be appropriate."

EMEA says that a "non-inferiority/superiority" trial comparing the study article to a reasonably comparative surgical therapy may be in order when the indication is for a lesion of greater than or equal to four square centimeters. For lesions smaller than 4cm2, EMEA recommends that the clinical trial be designed to show superiority "against the best standard of care," a position based on the fact that "no standard therapy has shown unequivocal efficacy." Given the difficulties with blinding, EMEA suggests a blinded evaluation of post-procedural patient data.

As for the duration of follow-up, EMEA indicates that three years might be longer than necessary, although this determination could be made after the trial is complete, assuming a "positive benefit-risk profile" is demonstrated during the trial. EMEA indicates it will take comments until Dec. 31.

Adventurous claims snag firm a warning

In an era of increasing FDA scrutiny of the medical device industry, the question of unapproved uses is taken very seriously ... most of the time. Anyone who spends enough time at the FDA warning letter page has reason to doubt whether everyone is getting the message, and the operators of netproductstore.com (Campbell, California) provide only the latest example of small firms that feel entitled to promote their inventory with a heaping helping of grandiosity.

FDA says in the Sept. 11 warning letter that the device was cleared as an electrostimulation device for a number of indications, including "relaxation of muscle spasms, prevention or retardation of disuse atrophy" and "muscle re-education." The product's 510(k) also includes an indication for "temporary relief of pain associated with sore and aching muscles in lower back due to strain from exercise or normal household and work activities." According to FDA, netproductstores.com was promoting the device for several other off-label uses, including anemia, headaches, neuropathy, arthritis, and impotence. FDA requested that the company cease the promotions. At press time, the company's owner, Bud Meachum, had not responded to a call for comment.

PTO to expand patent quality pilot

The U.S. Patent and Trademark Office has been the subject of a lot of ire from patent applicants due to long pendancy times, which are now said to average 36 months, and the agency has opted to respond by expanding a pilot program designed to reduce pendancy.

According to an Oct. 1 statement, the pilot allows applicants to sit down with PTO reviewers "prior to the first office action on the merits" but the first iteration of the pilot "was limited to two computer-related technology areas." In extending the pilot another six months starting Oct. 1, PTO has opted to expand the program to "additional technology areas," although the statement does not detail the technological areas included.

PTO says that the initial pilot demonstrated "that the patent process benefits when interaction between the applicant and the examiner are enhanced at the beginning of examination because patentability issues can be resolved early when the applicant and the examiner discuss them one-on-one." Early results were promising, PTO states, resulting in a six-fold increase in allowance rates "when compared to applications from the same technology area not involved in the pilot."

PTO director David Kappos said in the statement, "when people talk to one another and listen to one another they can quickly understand points of agreement as well as differences, and resolve those differences in real time." Kappos also said that the early results "are very impressive and show that interviews present a clear path to resolve issues and move prosecution forward quickly." PTO notes that such interviews had previously been granted at the discretion of the examiner.

MedCAC to expand meeting on afib

The Medicare Coverage and Evidence Development Advisory Committee (MedCAC) has opted to expand the number of technologies it will review in its Oct. 21 meeting to discuss the use of catheter ablation for atrial fibrillation. MedCAC had announced the meeting in August (Medical Device Daily, Aug. 18, 2009) but had indicated that only radio frequency ablation would be discussed during the meeting. The meeting will take place at the CMS building in Baltimore.

Mark McCarty, 703-268-5690;

mark.mccarty@ahcmedia.com