Medical Device Daily Washington Editor

The 510(k) program seems to have morphed into a source of never-ending controversy, with an application for a collagen scaffold by ReGen Biologics (Franklin Lakes, New Jersey) serving as the latest flashpoint. The company's application for the Menaflex, intended for use in the knee, was the subject of a November FDA advisory committee hearing (Medical Device Daily, Nov. 18, 2008), but the long history of the application and the company's recruitment of members of the House and Senate to intervene with FDA has fueled more speculation that the 510(k) process is profoundly out of kilter. However, company officials who spoke with Medical Device Daily are of the view that the long history of the application and resistance on the part of reviewers to a change in the proposed indication fueled the long-running dispute.

The Menaflex application cropped up in an article appearing in last Friday's edition of the Wall Street Journal, titled "Political Lobbying Drove FDA Process," which alludes to the fact that the company recruited members of the New Jersey congressional delegation in its dealings with FDA. Even after accounting for the possibility that the Menaflex application is at least somewhat out of the ordinary, the question of the validity of the 510(k) process cannot have been clarified by the article, which quotes former FDA commissioner Andrew von Eschenbach, MD, as saying that the 510(k) program is "out of control."

The former FDA commissioner was not available for comment for this article, but internal FDA e-mails suggest that von Eschenbach's role in the matter was facilitative of the application despite his comments to the WSJ.

The WSJ article includes a link to an internal e-mail that discusses a draft letter to be signed by von Eschenbach to ReGen officials that states that five temporary voting members – all orthopedic surgeons – will be added to the orthopedic and rehabilitation devices advisory committee in an effort to "assure you of its effective and impartial deliberations." As drafted, the letter would also have been sent to four members of the New Jersey congressional delegation, including Rep. Frank Pallone (D), who authored the Medical Device Safety Act of 2008 and chairs the health subcommittee of the House Energy and Commerce Committee.

According to company officials, one of the issues that dogged the application as it migrated from a PMA, which the company initially filed as an investigational device exemption in 1992, to three iterations of a 510(k) is a change of indication. The PMA indication was as a substitute for partial menisectomy, but the indication under the 510(k) applications was as a support for remaining meniscus tissue after a partial removal of torn cartilage.

On the other hand, the lead reviewer for the latest iteration of the 510(k) complains in an Aug. 14, 2008, memorandum that the latest 510(k) application "was requested to be reviewed in a total of three weeks," and that given other work, "the consult reviewers and I had approximately three days to perform a complete review."

ReGen's VP of regulatory affairs, John Dichiara, told MDD that the initial application in 1992 was for a PMA because "when ReGen started the IDE ... there were no resorbable surgical meshes used as a tissue scaffold." However, by 2005, when the company refiled the application as a 510(k) for the first time, "there were a lot of good predicates."

Dichiara also said that the conditions of the PMA filing may have stuck like glue to the minds of the reviewers. "I think the reviewers got in the mindset that this is a PMA device that is novel" because the initial indication was for superiority to partial menisectomy. "We changed the indication to one that lined up with predicates," namely to augment existing meniscal tissue.

The advisory panel did not engage in a vote on whether to recommend that FDA clear the application, but the consensus was that the device's safety profile was excellent, even if some members had questions about efficacy. However, Dichiara said at the hearing that the intended use was only "to support soft tissue," a claim he said the company's data backed up.

Also appearing at the advisory committee hearing were two well-known FDA officials. Dan Schultz, MD, director of the Center for Devices and Radiological Health, acted as the meeting proctor, a function typically handled by the head of the office that has jurisdiction over the device type. Presenting FDA's argument regarding the application was Larry Kessler, MD, the recently departed director of the Office of Scientific and Engineering Labs at CDRH.

The presence of CDRH managers may be seen as a clear indication of the intensity of the conflict between the company and the reviewers. Dichiara told MDD, "we felt there was an issue of staff bias. There was a moving target of objections" to the application. He said in an e-mail follow-up that the company and FDA reviewers held a meeting in February 2006, which was about two months after the firm filed the first 510(k), "with the sole purpose of clarifying the ... device's function," which was "necessitated by an FDA staffer communicating to ReGen that he believed the device was a prosthetic." FDAers present at the meeting were said to have failed to inform ReGen that the agency had mailed the company a not-substantially-equivalent (NSE) letter "with a date that preceded the meeting by four days." That letter, Dichiara states, arrived on the day following the meeting, and the director of the office of Device Evaluation (a position held by Donna Bea Tillman, PhD), is said to have rescinded the NSE letter. Tillman is also said to have requested that the review division "issue a request for additional information, consistent with CDRH's policy of generally not making NSE determinations in the first ... review cycle."

Dichiara's letter states that the additional information letter "did not request additional performance data ... but instead alleged there were no predicate devices for use in the meniscus." however, it should be noted that many of the meshes used in medical science, including one for use in the spine, also lack an anatomically specific predicate.

The second NSE, according to Dichiara, made the case that "use in the meniscus altered the therapeutic effect," and caused it to have "a new intended use." The third NSE letter compared the device to "partial menisectomy, which is a surgical procedure and not a predicate device," which he said constitutes an "illegal comparison." That comparison was the basis for the PMA.

FDA did not return calls for comment.