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].”
Daniel Schultz faced questions that illustrated the need for FDA reforms.
“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.”
Although his agency demonstrates few signs of it, FDA commissioner Andrew von Eschenbach again preached his commitment to openness and transparency. He made his comments on the Diane Rehm Show on National Public Radio on April 16. He agreed with Rehm that “there seems to have been a breach of trust” in the public's faith in FDA. The commissioner assured the listening audience that “first and foremost” they “need to know that there is only one purpose for FDA. That's to serve [people], not to serve politicians, not to serve industries, not to serve anyone else other than them.
Commissioner von Eschenbach promises openness.
“We need to be able to communicate more effectively how we're doing that,” von Eschenbach continued enthusiastically. To promote that, he said, FDA is redesigning its Web site “to make it more effective and more user-friendly as a way of communicating. My coming on this show today is an effort to be responsive, to answer the questions that the public has. We will continue to work to improve. No matter how good we've been in the past, we will get even better in the future.”
The hour-long program heard von Eschenbach repeatedly emphasize his commitment to a number of issues. He said he is committed to protecting and promoting the public health and to taking user-fee money from industry but never direction from it. He vigorously denied politicians' charges that “FDA is broken.” But perhaps most surprising, he championed the right of FDA employees to disagree publicly with the agency.
Told that his employees “fear speaking out, retaliation, that there's a lid on what they can say,” von Eschenbach told Rehm that he's facing the problem head-on. “[I have] gone throughout FDA since I've been there, having town hall meetings. One of the important messages that I continuously communicate is that my entire career as an oncologist has been based on realizing how important it is that we have rigorous, aggressive, open debate and discussion of different points of view and different opinions.”
Rehm pressed him about whether that open debate must be confined to what the media have referred to as the FDA team's locker room, or whether that debate may be aired in public dissent from FDA decisions. Von Eschenbach declared: “If there is ever any concern about the process and about the validity upon which those decisions were made, I believe everyone within the organization has a responsibility to speak out publicly and appropriately.” He said he would also welcome anyone who wants to speak directly to him. To that end, he has put some mechanisms into place to facilitate such communication. “That's a part of our commitment to protect and promote the public health,” he said.
FDA administrative law judge Daniel J. Davidson scolded both FDA and its target TMJ Implants Inc. (TMJI) in April for not settling their differences before now. He instructed them each to file motions seeking action and settlement. TMJI president and CEO Robert Christensen told me afterward that Davidson had obviously thoroughly read all the filings submitted by both parties and acknowledged that TMJI “makes very good devices.” Davidson seemed to want to know what the big deal was.
FDA has ordered TMJI to pay $630,000 in civil monetary penalties for failing to report 17 surgical intervention events as MDR events. The events involved TMJI's temporomandibular joint (TMJ) prostheses. Christensen, himself a TMJ implanting surgeon and inventor of the devices in question, says none of the events were attributable to the implants. And, he said, if posted on FDA's Web site, such MDR reports could be used in the marketplace against him, as though his devices were at fault.
In the April 16 hearing, Christensen told us, Davidson repeatedly cited MDR verbiage from 21 USC 360i. However, TMJI had relied on 21 CFR 803 when making reportability decisions. TMJI counsel Lynn Watwood made several objections to this, Christensen said. She said that 21 CFR 803 is preferred because of its definition of the term permanent injury.
On the other hand, 21 USC 360i has broader requirements for device manufacturers and importers. It says that they must establish and maintain records, make reports, and provide information as required by the HHS secretary. Such information is used to ensure that devices are not adulterated or misbranded and to otherwise ensure their safety and effectiveness.
Christensen told me that FDA presented no witnesses to present facts on how it determined that the 17 events were reportable under the MDR rule. “Where and who were our accusers or those whose decisions medically trump ours?” Christensen asked rhetorically via e-mail. “We have asked that question for the past two to four years and have never gotten any answer. Why are we not able to cross-examine our accusers?”
In summary, he said, it appeared that CDRH's strategy was to prove that TMJI did not have the evidence to make a 100% certain decision that its device did not contribute to the 17 events. Therefore they were reportable because 21 CFR 803 allows FDA to require an MDR if a device “may have” contributed to an event. CDRH reiterated that part of the definition of serious injury in the rule was “medical or surgical intervention.”
CDRH's position seems to be that manufacturers should report all events unless they are absolutely certain their device did not cause the event, Christensen said. If this were the case, he noted, “it would seem [to] go against 21 USC 360i requirements, which state that FDA ‘shall not impose requirements unduly burdensome to a device manufacturer.'”
For its part, Christensen said, TMJI attempted to demonstrate that the company follows a process that satisfies the law. The purpose of that process is to evaluate each adverse event and to determine whether the received information reasonably suggests that a medical device caused a serious injury.
The two apparently irreconcilable and divergent approaches are what Davidson wants the parties to reconcile between themselves by June 15.
FDA has classified a HoMedics recall involving 292,000 heating pads as Class I. The recall relates to the potential for heating pads to have a loose connection, which may cause the units to short-circuit. “This problem may pose a risk of burn injuries or fire as well as damage to the heating pad itself or to materials (like bedding and furniture) which may be in contact with the pad,” FDA said.
The agency cited consumer complaints of user burns and fires to bedding, clothing, and houses that were started by the heating pads. Class I recalls are for products that predictably could cause serious health problems or death.
The agency became aware of the heating pad problems after an inspection revealed quality system deficiencies related to design controls, complaint handling, and corrective and preventive actions. Complaints were reviewed during the inspection and HoMedics agreed to the recall after “discussions with FDA.”
An FDA reinspection at Guidant Corp.'s rhythm management facility in St. Paul, MN, last December resulted in no adverse observations. The agency has lifted all restrictions that had been imposed as a result of a warning letter that a year earlier had cited numerous CGMP violations.
Boston Scientific said the reinspection included an assessment of its implementation of quality system improvements in response to the warning letter. (Boston Scientific now owns Guidant.)
Since the warning letter, Guidant has warned doctors about battery voltage problems with implantable defibrillators. And, in April 2007, the company recalled 73,000 defibrillators.
FDA has issued a question-and-answer document on that recall. The document says a faulty capacitor in the devices can cause the batteries to deplete sooner than expected. It can be found online at www.fda.gov/cdrh/news/guidantrecall.html.
“Most patients will not be affected by this recall,” the document says, “but patients with one of the recalled devices should contact their physicians about what steps to take next.” The document answers questions about problems with the devices and what patients should do. It also explains how physicians can determine whether batteries are depleting too fast and how this recall relates to other Guidant problems.