FDA Abused Power, ReGen Biologics Exonerated

In the biggest case challenging FDA regulatory authority of this young century, the FDA’s power has been narrowed and ReGen Biologics Inc. has been vindicated over allegations that the company used improper political pressure to influence the FDA’s 510(k) clearance of Menaflex, the company’s collagen scaffold.

No Power of Rescission

On September 26, 2014, the U.S. Court of Appeals for the District of Columbia said the FDA cannot make up the power to rescind 510(k) clearances. They further said there is nothing wrong with asking congressional leaders to intervene on your behalf with government agencies. In fact, said the Court, it’s the job of elected officials to advocate on behalf of their constituents.

The FDA had argued that because there was misconduct, they had a right to rescind. The Court didn’t buy that saying, “FDA’s inability or unwillingness to identify [any] wrongdoers is an indication that, in fact, no…misconduct occurred.”

The Court ruled that the FDA went outside the law by rescinding the 510(k) clearance it had granted the company. If the FDA wants to change a device’s classification, the agency should use its existing authority to reclassify a device and provide proper notice and opportunity for comment.

In short, the Court said the FDA can’t grab power just because it’s convenient and makes their job easier. “FDA obviously thinks notice and comment is unnecessary here, a not-uncommon sentiment among agencies that want to take action more promptly.”

Safe and Effective?

While this is a big win for the industry, the fate of the company and patient access to the device is still in question. The FDA can still decide to reclassify the device and force the company to go through a PMA (pre-market approval) application process after already spending over $30 million to get clearance.

That would be a shame because the Menaflex has already been through unprecedented two expert orthopedic panel meetings. Both panels agreed the device was as safe as its predicate, with one panel having some question over its effectiveness.

Industry Trade Group’s “Potomac Syndrome”

Given that this is a big win for all medical device manufacturers we would expect the two industry trade groups, AdvaMed and MDMA (Medical Device Manufacturers Association), to cheer the decision. We contacted both trade groups for comment. AdvaMed said they would have no comment and the other didn’t reply to us at all.

If the abuse of FDA’s police powers in this case wasn’t bad enough, both trade associations stood by as the FDA pummeled ReGen into bankruptcy. Clearly they did not see this as their fight or they saw no benefit in antagonizing the FDA with whom they need good relations to lobby on behalf of their members. Maybe it’s a kind of “Stockholm Syndrome” we should rename “Potomac Syndrome.”

Failure to Protect and Promote

But back to the FDA’s misdeeds.

It is the job of the agency to “protect” and “promote” public health. They failed on both accounts in this case by failing to get a safe device to patients who risk getting arthritis after a meniscectomy.

Kevin Stone, M.D., inventor of the device, filing the first patent in 1986, told us that the data is “overwhelming” that meniscectomy leads to arthritis. He added that repairing or regenerating the meniscus is the only method of restoring the normal mechanics of the knee.

He believes tens of thousands of patients were basically sentenced to years of arthritis pain because they did not have access to the device in the U.S. Patients and Europe and Asia have had access to the device ever since its introduction.

What does this all mean for getting new devices to patients?

Road to Redemption

Before we turn to Mark DuVal, a well-known private industry attorney, to answer that question, let’s review the torturous road the FDA forced ReGen to travel for clearance as described in the Court’s opinion. The story of that journey to clearance is a shameful tale of, at worst, willful abuse of power, and at best, bureaucratic ineptitude.

ReGen began commercialization efforts in 1993 for the device, a crescent shaped surgical mesh made of bovine collagen intended to reinforce and repair the knee cartilage remaining after knee surgery and to provide a scaffold on which new tissue could grow.

In 2004, the company submitted a PMA. But then determining that the device was substantially equivalent to other meshes on the market, it quickly withdrew the PMA application in 2005 to seek 510(k) clearance.

FDA reviewers disagreed and issued a NSE (Not Substantially Equivalent) letter. The company came back in late 2006 with a revised label. Again the agency issued an NSE letter.

Substantial Equivalency Argument

The company ran out of administrative appeals and vehemently disagreed with staff that they believed were misapplying equivalency rules. (A later FDA report, co-authored by Jeff Shuren, M.D., JD, cited that its own lawyers agreed with the company.) So they went to their elected officials in Congress, who wrote to the FDA Commissioner expressing concern over the procedure used by the agency.

The FDA, through Dan Schultz, M.D. the head of CDRH (Center for Devices and Radiological Health), then met with the company. He advised them to submit a new clearance request with additional revisions. The company did so in 2008. Again the review staff said, no.

At this point, Dr. Schultz decided to convene the agency’s orthopedic panel of outside experts. The panel concluded in 2008 that the device was as safe and effective as the predicate. Dr. Schultz then issued a letter finding substantial equivalence.

FDA Goes Rogue

Then all hell broke loose. The Appeals Court noted that The Wall Street Journal published an article alleging that political pressure had “skewed FDA’s review process, ” and Senator Charles Grassley contacted the FDA raising concerns about ReGen’s role in the process. Other members of Congress joined in.

Then, in April 2009, as ReGen was about to begin selling the device in the U.S., a group of FDA employees wrote a letter to President Obama accusing Dr. Schultz and the FDA Commissioner of improperly influencing the results of the agency’s review.

Internal Investigation

The newly appointed Acting FDA Commissioner ordered an internal investigation and a report was issued on September 2009.

According to the Court, that FDA report identified “multiple departures from processes, procedures, and practices” that raised “serious questions about whether the integrity (as well as the quality) of the review process was compromised.”

The report criticized ReGen’s access to high-level FDA officials, and those officials’ involvement in the decision making process; communications between members of Congress and the FDA Commissioner; and ReGen’s level of involvement in the expert panel proceedings.

“Although the report stopped short of concluding that the review process had been compromised, it recommended reevaluation of Dr. Schultz’s decision to clear the Collagen Scaffold, ” wrote the Court.

Shuren Replaces Schultz, Rescinds Clearance

Dr. Schultz suddenly resigned and a new team was appointed to review the device. Dr. Shuren took Schultz’s place as head of the CDRH.

Not surprisingly, the staff again concluded the device was not substantially equivalent and Dr. Shuren convened a second expert orthopedic panel. This panel agreed with the first panel over the safety, but had some concerns about its effectiveness.

In October 2010, Dr. Shuren notified ReGen that the clearance “was in error” and an official rescission order followed in March 2011.

ReGen Fights Back

ReGen went bankrupt. However, institutional investors in the company kept the product alive and filed suit against the FDA, arguing the rescission was unlawful and that the FDA should have followed the reclassification route if it wanted to reclassify the device.

The U.S. District Court agreed with the FDA and ReGen, now called Ivy Sports Medicine, appealed. Ivy won the appeal on a 2-1 vote of the judges.

Industry Impact

Mark DuVal says the FDA “again misjudged its strength and position…inventing its own rights is a common theme with this FDA Administration.”

He says the decision “provides a ray of hope that FDA cannot make-up-rules-as-they-go-along…just because the new administration has a differing scientific and regulatory opinion (and possibly another political agenda).”

The impact of this case, says DuVal, cannot be underestimated on a number of levels.

He says the FDA “not infrequently” exceeds its statutory and regulatory authority often granting to itself powers and interpretations of law and regulations well outside the scope of that actually given to them. “FDA has had its interpretations of law and regulations checked by such representative and famous cases as the Washington Legal Foundation case, the IMS Health case and the Caronia case, all First Amendment cases. “

It also lost the Utah Medical case as it relate to its authority to dictate specific CGMP/QSR requirements to a medical device manufacturer. In the Prevor case, DuVal says the court did not agree with FDA’s interpretation of how to determine the definition of “primary mode of action” of a combination product. “And now we have the Ivy Sports/ReGen case.”

Keeping Vigilant

DuVal cites a number of current situations, including the agency’s attempt to introduce benefit-risk criteria into the 510(k) program in a July 15, 2014 proposed guidance. “The underlying benefit-risk of any device is presumed and has already been accepted in the decision to clear the predicate device. There is no need to make a benefit-risk determination in a 510(k), yet FDA has created it out of whole cloth, ” warns DuVal.

“We must continually keep the natural evolution of any bureaucracy in check because it will continually expand interpretations to grow its jurisdiction and authority and make the regulatory framework more complex and need more people to administer it. We often wonder if it is regulatory fiefdom-building or regulatory boredom, or both, that drives this need to create more, increasingly-complex rules. This in a great sense is what we fight when we fight these individual battles with FDA.”

Hopefully, says DuVal, the FDA will “rein in its thinking—but don’t count on it.” His pessimism is informed by the fact that going through the FDA appeals process can be futile because it typically upholds the decisions of its rank and file. The only other alternative is to go to court, which is far too time-consuming and expensive.

“For that reason companies often take a more practical, yet painful, decision to roll over and acquiesce to the Agency’s (often incorrect or stretched) position, ” added DuVal.

DuVal: “Return to Old-Fashioned Rulemaking”

He hopes that this is a clarion call for industry to request that Congress restricts the Agency’s “continued proliferation of guidance documents and return to old-fashioned, more thoughtful and deliberative rulemaking. At a minimum, we need to bolster the manner in which guidance documents are proposed and finalized. Otherwise industry simply falls victim to an agenda-driven agency that is drunk on its own perceived power.”

Hope for Patients

It’s bad enough when the cop on the beat whose sworn duty it is to “protect” and “promote” our welfare goes rogue and unlawfully beats up the smallest kid on the block, it’s equally bad when the bigger kids with a lot to gain and the ability to help, stand by and watch.

Let’s hope this is a clarion call for all involved. But more importantly, as Dr. Stone pointed out, let’s hope patients are given access to a device that can help them without leaving the country.