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The time for revising FDA has arrived. Through the vehicle of user-fee reauthorization, the remaking of this agency is likely to be the most extensive in its history. Tied onto this reauthorization is a list of fixes that reach far beyond merely charging industry for product approvals.The proposed changes are detailed and cover many areas. For example, aggressive performance goals have been set for FDA decision making in product reviews. Postmarket surveillance will be modernized to include electronic databases. Pediatric devices will be approved and tracked, and humanitarian device exemption requirements will be modified. The reauthorization also will address the openness and transparency of FDA processes. Finally, it will try to bridge gaps in product development and innovation though a new nongovernment, nonprofit Reagan-Udall Foundation.

This frenzied legislative season will see many groups try to help reconstruct a regulatory scheme that many regard as broken. Expect industry lobbyists, consumer and patient groups, watchdog activists, media reporters, and others to participate.

But the pending legislation will not stoop to cover certain details. The wide discontent with FDA even gets down to mundane matters like mail handling and support staff motivation.

This discontent came through at the Regulatory Affairs Professionals Society (RAPS) Horizon conference. CDRH director Daniel Schultz appeared before an industry audience at the conference, which took place in San Francisco in March.

Schultz presented his familiar center performance and outlook facts and figures. He also expressed gratitude for a congressional continuing resolution that had just given him slightly more resources for this year than last. Then he took questions that quickly revealed the need for agency reforms.

Alameda device consultant Craig Coombs took the floor to talk about “low-hanging fruit” that was not included in Schultz’s presentation. Coombs described “niggling things” that show lack of support from some FDA staff “way below the reviewers.” Over the past few years, Coombs reported, “after a letter is dated, it still takes almost two weeks for us to get it through the mail.”

Schultz quipped, “The ponies aren’t running as fast as they’re supposed to?”

As laughter erupted, Coombs raised the ante. “Speaking of ponies, I was working with a reviewer this last year who’s in the White Oak facility. He had to quit work early, every day, to drive his mail over to Rockville. The interoffice mail couldn’t get it there in a timely manner.” Schultz acknowledged that, without making any promises, this is “a problem we should be able to deal with in 2007.”

Coombs’s best example of support staff incompetence brought the house down. “I supported a 510(k) for an aortic cannula,” he told Schultz. “In spite of how many times I told the staff to [correct the spelling], I ended up getting a 510(k) clearance for an erotic cannula.”

As the laughter subsided, Schultz deferred to 510(k) staff chief Heather Rosecrans. “If you do have a typo or that kind of thing on your substantial equivalence letter, if you just let my office know, we work with the division, and I’ll have it corrected right away,” she said. As for mail delays, she advised sending an e-mail either to her or to Schultz. “We are willing to fax every final decision.”

The issue wasn’t going to slip away that lightly, however. Another consultant, Bob Morton, formerly of CDRH, noted that letter delays have “gotten worse recently.”

Without breaking stride, Morton changed the subject to third-party inspections, for which Schultz has argued repeatedly and unsuccessfully. The last time Congress revamped FDA—with the Medical Device User Fee and Modernization Act of 2002—such inspections were authorized. “What’s the incentive for my clients to do a third-party audit?” Morton asked. “Today, many of your investigators aren’t visiting at all. [Firms] that have high-risk devices you are visiting anyway, and why should they do it? So far, I haven’t been able to counsel them on a good reason [to do such an audit].”

That’s a real fair point,” Schultz acknowledged, as though he hadn’t heard this objection many times before. Then, he spoke slowly and carefully as he thought it out. “I think that the incentive ultimately would be that, especially for companies [with] wide global markets…that have people coming in and inspecting your facilities it seems like every other week, we could ultimately move to a single inspection that would cover both the ISO as well as the QSR.”

But his own logic seemed not to reach his point. “You’re right,” he admitted, “if a company is going to have an FDA or an ISO inspection anyway, there’s no incentive. For companies that are not expecting to have an FDA inspection any time in the foreseeable future, again, the incentive is minimal. That’s what we are trying to look at, for this Canadian pilot. We’re actually trying to look at the list that we have, and the list the Canadians have, and see whether there are companies on both lists [that] are targets for inspection over the same time period, where hopefully this would help everyone.”

Morton asked for a follow-up. “I’ve worked with companies, helping them recover from a warning letter. During that period, they go through an ISO audit and pass. These are not the same things, and the companies know it. They’re not going to say, ‘Well, since you’re here, tell FDA what’s wrong.’ I wouldn’t spend a lot of time on it [third-party inspections]. I’d spend time and money on getting more trained investigators out there.”

“Fair point,” Schultz acknowledged, again. “Thank you.”

Then came a question from a Medtronic employee. The questioner asked him to “shed some light” on a previous speaker’s “mention that all final guidances by FDA go through the White House.”

“I don’t know whether I should comment on that,” Schultz answered carefully. “I think we want to have a process that allows us to develop guidance and get it out there in a timely fashion. I think you want appropriate levels of review in order to make sure that the guidance is well done, meaningful, and helpful. I think I’ll stop there.”

– James G. Dickinson

Over the past three years, the relationship between FDA and the medical device industry has seemed to grow closer. The agency’s highest officers have expressed more appreciation toward industry and its various efforts. This apparent closeness is, of course, notwithstanding some isolated experiences, mostly with small so-called maverick companies willing to buck the system.Most recently, the new spirit toward industry showed itself in the words of Commissioner Andrew von Eschenbach. He spoke via a prerecorded satellite feed to AdvaMed’s annual meeting in Chandler, AZ, in March.

“It has been my experience,” he said, “that we have the opportunity to serve large companies that are addressing macro issues of complex product development as well as small companies that are really at the forefront of entrepreneurial innovation.” This notion of FDA in a service role for an industry it regulates is new. In my view, it flows from the introduction of user fees paid by industry for the review and approval of new products.

Indeed, barely a week after his AdvaMed remarks, von Eschenbach appeared before the Senate Health, Education, Labor, and Pensions Committee. There, he said that drug user fees are “specifically intended to be fee-for-service.” His testimony to the senators stressed that industry fees don’t sway FDA’s scientific decisions. However, von Eschenbach left unaddressed the vast nonscientific landscape on which FDA regulators and fee-paying industry people routinely make contact. That’s where some industry watchers assert that a change of attitude has occurred among high-level FDA managers. That’s also where the notion of FDA providing a service to the device industry has taken root.

The new dynamic’s origins may be traced back to von Eschenbach’s predecessor, Lester Crawford. In March 2004, he proclaimed—at AdvaMed’s annual meeting—that his door was always open to industry. He also said that communication was the name of FDA’s game. “We’ve had some great communicating commissioners,” he bragged, “but I’m still the only one that ever has had a listed phone number. So give me a call!”

Of course, even for FDA commissioners, talk may be cheap. Kevin Cornwell, CEO of Utah Medical Products, took Crawford up on his invitation and spoke to him twice. Cornwell says the commissioner twice committed to follow up but did nothing to avert the agency’s legal action against his firm. This may raise a question about how useful to industry FDA commissioners really are.

Three years further down the FDA-as-servant road, von Eschenbach made his long-distance debut at AdvaMed atop the momentum of a just-concluded negotiation between FDA and industry to reauthorize MDUFMA.

In his video, von Eschenbach was effusive in his gratitude. “I wanted to take this opportunity to speak to you as the FDA commissioner,” he said, “to reaffirm how much I value the importance of the work that you are doing.” He said he particularly valued the strong partnership that has been formed between AdvaMed and FDA.

He briefly described how their interactions benefit patients. Then, von Eschenbach said he was “very, very gratified by the recent collaboration between industry and FDA as we have worked together to renew authorization of MDUFMA. I’ve been particularly gratified and grateful for the support and leadership of the AdvaMed board in helping to seek constructive solutions for many of the challenges that we have to face.”

Von Eschenbach described how the new user fees would improve CDRH’s reviews of AdvaMed members’ products and enhance FDA expertise. By means of these improvements, patients will benefit through FDA’s service to all kinds of device makers. “FDA has a mission that’s directed across the entire continuum of the industry,” he said, “and collectively that will enable us to be sure that we’re bringing the most effective products to the marketplace.

He stressed that FDA and industry working together can save lives and can transform healthcare. “It’s a privilege for me to thank you for the collaboration in the effort that we are embarked upon to make that a reality,” he continued.

He again praised AdvaMed’s support of the MDUFMA “legislative package.” He said it creates “what we believe is an appropriate and exciting opportunity for both FDA and industry to have the resources that will enable us to enhance the regulatory process. I am committed to that relationship and to that outcome.”

He also promised FDA’s full commitment to all the new FDA review performance goals set out in a separate letter to Congress alongside the MDUFMA reauthorization agreement. “If FDA says we will do it, we will do it,” von Eschenbach said. “Let me add that [we’re] not just committed to meeting the goals; we’re committed to exceeding the goals. I believe we have the opportunity for continuous quality improvement and continuous performance improvement at FDA.”

Meeting the goals will not only improve the MDUFMA relationship, von Eschenbach said. “It’s really our commitment to bring to patients, the public that we serve, solutions to the problems that threaten their health and their lives.” Doing that more efficiently and more rapidly, he said, is core to FDA’s mission. “That is a commitment that you and I share together. I look forward to a continued dialogue and conversation, and most importantly I look forward to the very collaborative and cooperative relationship that exists between FDA and the device industry—and particularly, AdvaMed.”

There was much regulatory good feeling spread throughout the session. By the time CDRH director Daniel Schultz and CBER director Jesse Goodman had finished their presentations, one hopeful listener was moved to sound out the prospects for even better news.

Could we do away with advisory panel reviews? The advisory panel review process for new devices can seem “like going to Vegas,” he said. “I’m curious to hear your perspectives. Do you think it’s a process that still serves its original intended purpose or one that needs to be embalmed or changed?”

But review changes were not in store. Although Schultz thought it a “great question,” he quickly reverted to FDA conventional wisdom. Panel review still serves a necessary purpose, he said, “from a number of different aspects. One is that it allows us to bring in specific expertise in a whole variety of areas that we may not have internally. Two, it provides an outside look at products. You may have been spending 10 years of your life developing the product, and we may have been spending five years of our life looking at that product. I think at that point, everyone develops a little bit of tunnel vision.”

Having others look at it from a public health perspective “is a good thing,” Schultz said. Panel reviews are important from both a communications and a public trust standpoint. “It’s unique to our regulatory system, and a credit to it, that we do lay everything out in public.”

Goodman said he agreed “absolutely. Transparency is very beneficial to everyone.”

User fees have engendered a new attitude toward industry at the highest levels of the agency. However, the historic devotion to burdensome public transparency lingers on, to the cost of product sponsors and to the education of bystanders.

The question of the effect of commissioners on FDA operations remains unanswered. Nevertheless, a new tradition of FDA service to industry is being forged, at least at the upper-management level.

– James G. Dickinson

FDA’s impending reorganization of its field offices to “will be massive,” noted Mark Roh, FDA’s deputy regional director for the Pacific Region. “When we’re done, we won’t look like we look today,” said Roh. He spoke at the RAPS conference in San Francisco in March.

In FY 2008, FDA will embark on a rebalancing and consolidation of offices, and this rebalancing will result in the closing of certain laboratories. Roh noted that the planned restructuring is still proposed, but that Congress is “very close to signing off on it.”

In FDA’s new structure, the regions will be the interface with the district and headquarters, and the district offices will become part of FDA’s new inspection compliance directorate. All of the laboratories will be removed from the districts and will become part of a new science directorate.

“This is a big change. It means the dissolution of the regional offices and the dissolution of several positions within the regional offices,” said Roh. He said it means reassigning all the regional positions to different offices and probably downscaling a few positions that are currently in place.

The biggest change—and one that Roh said has caused the most consternation—is that the 20 compliance branches are going to be fused into 10. With this consolidation, FDA will also change the way it handles compliance issues.

Right now, many field compliance issues go directly to the Denver office of enforcement and bypass the Office of Regulatory Affairs (ORA) Office of Enforcement, explained Roh. “Oftentimes there have been abuses. We constantly blame Denver for turning down cases,” he said.

According to Roh, the new structure will result in FDA putting forth stronger cases. Because the district will be working more directly with the Office of Enforcement in ORA, Roh said, “when we feel we have a case to take forward, they will be with us all the way. They will actually be pushing it.”

Under the new system, most actions will go through the Office of Compliance in FDA’s ORA before they go to [CDRH], Roh said.

“They will go to the ORA Office of Enforcement for quality purposes to make sure that we did it right and that there’s enough evidence to do whatever it is we are proposing to do.” Roh went on to say that the Office of Enforcement in ORA will then carry the message to [CDRH} with its recommendation, and "they will work closely together."

Roh emphasized that FDA's purpose in reorganizing its offices is to better serve the public and the industry. "The bottom line is that we want the products we regulate to be safe and effective," said Roh. "Our primary values are the ethics of our operation. We are very proud that [consumers] have consistently voted us at the top of consumer trust, and we want to stay there. And you demand that, too.”

This is the biggest structural change at the agency in decades. But, what may be good for FDA could be a bureaucratic nightmare for you and your company. Massive is an apt description. With half the number of compliance branches, you most certainly will see a difference. Make sure you let FDA know what these changes will mean to you.

– Sherrie Conroy

FDA on June 4 announced the formation of a 15-member committee to advise it on how to improve communication regarding risks and benefits of medical devices and other products the agency regulates. The committee is based on a recommendation from the Institute of Medicine.There’s no question that the agency needs to do a better job in this regard. The public has mistakenly come to understand that a product with FDA approval should have zero risk. This perception is part of why the agency has taken such heat over products that have proven too risky after approval.

The question is whether the goal of clear, concise, consistent, and contextual communication can be achieved by a committee of 15 people. To quote the FDA release: “The advisory committee will be made up of 15 voting members that include experts and public members who are not affiliated with the FDA. Experts will include authorities knowledgeable in the fields of risk communication, social marketing, health literacy, cultural competency, journalism, bioethics, and other relevant behavioral and social sciences. Public members will include those who can provide the perspective of users of FDA-regulated products, such as consumers, patients, caregivers and health professionals.”

That’s a lot of voices, all with different agendas. This has the potential to be “committee hell.” I foresee a group of people that aren’t going to be able to agree on anything, which wouldn’t make FDA’s message any less muddy than it is today. The idea is a good one, but a large and unwieldy committee will make execution difficult.

– From MD&DI’s blog.

Dr. Steven Nissen, head of the Cleveland Clinic’s department of cardiovascular medicine, has made a name for himself as an FDA watchdog in recent years. He was one of the first to raise alarms about safety issues for Vioxx and drug-eluting stents. Today’s Boston Globe has an interesting read on why Nissen has become such a prominent voice. His critics say it’s because he’s angling to become the next FDA commissioner. (Beltway insiders expect Andrew von Eschenbach, a friend of the Bush family, to step down when President Bush leaves office.)

His critics seem to fear that a Nissen-run FDA would return it to the dreaded Kessler years, during which the approval process for devices and drugs was glacial and new treatments didn’t get to patients nearly as fast as they should have. I don’t think Nissen is so obtuse as to want to swing the pendulum that far in the other direction. But if the Democrats win the White House next year, there will certainly be pressure to nominate someone who’s not nearly as friendly to industry as von Eschenbach, and Nissen could fit the bill.

– From MD&DI’s blog.