FDA commissioner Margaret Hamburg has hit the deck running. In her first 25 days at the helm, she appointed an internal task force to examine the state of the agency's transparency, published a definitive article coauthored with principal deputy commissioner Joshua Sharfstein on the preeminent role that public health will play in her agency, testified on Capitol Hill, and promised that she would take a “hard look” at “obvious problems” in FDA's dysfunctional CDRH.

Hamburg said during a battery of one-on-one interviews in June that addressing previously reported controversies over the center's processing of 510(k) submissions is a high priority. In the weeks before her arrival, as reported in this column in the July issue, Sharfstein had ordered an internal investigation of whether the integrity of one of those premarket clearances, for the ReGen collagen scaffold, had been compromised under political pressure. There is a list of other 510(k)-cleared devices that might be similarly investigated—not necessarily for political pressure but for reviews that were insufficient in other ways to adequately ensure safety and effectiveness.

Interviewed by the Wall Street Journal's Alicia Mundy, Hamburg said the review of CDRH's performance is part of her overall goal to “reinvigorate” the agency and enhance its credibility with the public and policymakers. In an interview with Gardiner Harris of the New York Times, Hamburg said that she will work toward improving the agency's science base and “assuring that all voices are heard in terms of evaluating the science, and that decisions are made based on available data and evidence without undue or inappropriate interference from other sources.”

Hamburg promised to be tougher on enforcement and to “hire new leaders”—without being specific. An earlier commissioner who was tough on enforcement, David Kessler, said in a recent interview that he has talked with Hamburg, and he described CDRH as “dysfunctional,” and “in meltdown.” On my own Web site in March, I called for CDRH director Daniel Schultz's removal from office for his failure to control review and enforcement problems like those now under investigation.

As if attempting to ride the rising tide against him to safety, Schultz appeared before the Medical Device Manufacturers Association (MDMA) in June to discuss CDRH's plans to use communication, transparency, and fine-tuning to build trust back into the system. These are all buzzwords stemming from the new Hamburg-Sharfstein leadership.

Schultz told his audience that FDA and industry have not done a very good job of communicating to the public that the 510(k) process is not the “mindless rubber stamp that some people are making it out to be.”

Schultz acknowledged that the new leadership at FDA watches the newspapers and listens to what comes down from Capitol Hill, “so we are going to try to work with them to explain what [the 510(k) process] is and what it isn't in a way that makes sense. That doesn't mean that we are just going to be able to say everything is fine and leave things alone.

“I think there are situations in which we started with one device a long time ago and ended up some place very, very different,” Schultz continued. “And it is really hard to explain the entire complicated path that got us from where we were in 1976 to where we are in 2009.” He said that the center needs to do a better job of defining that path and making it much clearer how decisions were made along the way based on the data and risk analyses.

“There are a lot of people who don't trust the system and we need to build that trust back up. Part of it is communication, part of it is transparency, part of it is probably making some necessary changes to tighten the system up,” Schultz told the audience. “We need to take a hard look at using the different regulatory tools to their maximum use and perhaps the de novo process is one that has not been used as effectively as it could be.”

On the issue of transparency, Schultz said this will be the buzzword for the next four years. “Clearly the message we have gotten from the commissioner and deputy commissioner…is that we need to do a better job of making our process more transparent,” both in terms of the regulatory process and in terms of the data (positive and negative) being collected. Schultz admitted that the transparency creates challenges, including “how to make the process more transparent while at the same time not impeding [device] development that relies on some degree of propriety and keeping your own information.”

Public expectations are very high right now, Schultz told the audience. There continue to be news stories about devices and “the sense is that we are in some ways victims of our own success. Rates of adverse events that would have been laudable 10 years ago are now not considered to be that.”

According to Schultz, as devices become more sophisticated, the expectations have become increasingly higher, which creates a standard of perfection for every device that comes on the market. “We need to be able to address that, and the answer is we need to do a better job explaining risk and benefit in a way that we really haven't done in the past.”

Schultz also discussed the advisory committee process and the level of expertise needed on advisory panels. Read other highlights from Schultz's appearance at MDMA's meeting at www.transformingfda.com.

Probe Urged on CDRH's Role in AM2PAT Case

The Project on Government Oversight (POGO) has called on FDA commissioner Margaret Hamburg to ask the HHS inspector general (IG) to look into FDA's role in the AM2PAT case in which tainted syringes were manufactured and sold.

In a June 6 letter to the new commissioner, POGO said that although “senior officials of AM2PAT were clearly responsible for this tragedy…FDA bears much of the blame for allowing it to happen…. A year before you took office as FDA commissioner, many of the facts in the AM2PAT case were well known to the agency. However, up to now, FDA's role in the AM2PAT case has not been publicly acknowledged either by FDA or the inspector general.”

POGO said that FDA's regulatory failure in the case was particularly clear-cut, as was the harm inflicted on patients. It said that many of the details have been unearthed and confirmed by a federal prosecutor and are available in court documents and media accounts.

“A report by the HHS IG on this well-documented, fairly straightforward case would throw light on the institutional weaknesses at FDA that led to regulatory failures in other episodes that are more complicated and more difficult to investigate,” POGO's letter said.

Part of the reason for FDA's regulatory failures in this and other cases is that the agency habitually maintains a relationship with manufacturers that is too collegial and too tolerant, the group said in the letter. POGO said that there is a reluctance within FDA to take corrective action stronger than a warning letter even when stronger action is clearly warranted, as it was at several points in the history of the AM2PAT case. An additional factor cited by POGO is what it termed the grossly inadequate resources available to FDA for inspection and enforcement.

Pogo's Recommendations

The Project on Government Oversight (POGO) made recommendations for FDA in its June 6 letter to Hamburg. As a result oflessons learned from AM2PAT, POGO said, FDA should:

•Pay more attention than it now does to newly established firms making medical devices.

•Consider recommending or requiring an immediate change in 510(k) policy so that when the manufacturer of a Class II or Class III device files a 510(k), it must include information such as test data on devices that will be produced and marketed plus information on manufacturing facilities and personnel.

Medtronic Pacemaker Recall Rated Class 1

FDA says recent notifications to healthcare professionals and patients by Medtronic on certain Kappa and Sigma pacemakers are considered a Class 1 recall. “These devices may fail due to a separation of wires that connect the electronic circuit to other pacemaker components, such as the battery,” the agency said in a June notice. “Patients with malfunctioning pacemakers may experience a return of symptoms associated with abnormal heart rate, such as fainting or lightheadedness. In rare cases, pacemaker-dependent patients may experience serious injury or even death.”

Worldwide, there have been more than 1.7 million Kappa or Sigma pacemakers implanted in patients. The recall targets only about 21,000 of these, most of which have been implanted in patients for five years or longer. The affected pacemakers are Kappa Series 600/700/900 and Sigma Series 100/200/300. The agency says patients with these models should determine whether their pacemaker is part of the recall by contacting Medtronic at 800/505-4636 or by visiting www.kappasigmasnlist.medtronic.com.

FDA Cites Software Maker for Violations

FDA has issued a warning letter to R4 LLC after an FDA inspection in March found quality system violations at the firm's Strongsville, OH, facility. This is where the company manufactures the R4 Acert perinatal reporting software. According to a May 11 warning letter issued by FDA's Cincinnati district office, violations cited include:

•Failure to establish adequate management controls to ensure that an effective quality system had been established and maintained. There were no written corrective and preventive action procedures, design change control procedures, complaint procedures, or medical device reporting procedures. Employees had not received training on the quality system requirements.

•Failure to establish and maintain a design history file that demonstrated the design was developed following the design control requirements.

•Failure to perform risk analysis for the Acert software.

•Failure to include the signature of the approving official for documents. The firm created and stored all written information as electronic files and did not keep any hard copies of the records. The firm's electronic documentation system did not meet system validations etc.

The firm was told to take prompt action to correct the violations detailed in the letter.

Revoke LASIK Device Approvals, Patients Urge

CDRH guidance ostensibly limits allowable medical device “complications” to 1%. But the center has approved lasers used in LASIK vision-correction surgery that exceeded a 20% complication rate in the clinical studies that supported their marketing applications.

These findings are the basis of a June 11 request by dissatisfied LASIK patient Lauranell H. Burch to revoke the devices' approvals. She is molecular genetics core facility director at the National Institute of Environmental Health Sciences.

Part of an informal network of similarly dissatisfied LASIK patients who claim the procedure has permanently injured them, Burch made the request in an earlier petition to FDA that she said is being ignored. She also mentioned the revocation request in identical letters to the Government Accountability Office and the HHS inspector general.

The network escalated its campaign in June to have FDA upgrade the devices' labeling and implement medical device reporting (MDR) requirements against ambulatory surgical facilities performing LASIK. Burch's letters told the overseers that FDA “has been grossly negligent and has placed patients' interests secondary to interests of medical device manufacturers.”

The letters were sent one day after an appeal for presidential intervention from another activist and injured patient, Scott A. Tolchin. He is seeking a moratorium on LASIK eye surgeries due to an alleged increased rate of adverse events related to the procedure. These events, he said, include depression, posttraumatic shock disorder, and suicide.

Burch said that about 700,000 people a year undergo LASIK, “largely as a result of aggressive and often-misleading advertising.” She did not mention a cautionary letter sent in May by CDRH compliance director Timothy A. Ulatowski to eye-care professionals on their marketing claims.

In that letter, Ulatowski said the center “believes that eliminating deceptive or misleading health-related advertising claims is an important part of protecting the public health.” He said that advertising and promotional materials for FDA-approved lasers used during LASIK procedures must be truthful, properly substantiated, and not misleading. Ulatowski said that

In determining whether the advertisement is misleading, FDA takes into account not only representations made or suggested by statement, word, or design, but also the extent to which the advertisement fails to reveal facts material in the light of such representations, or material with respect to consequences which may result from the use of the device to which the advertisement relates under the conditions of use prescribed in the advertisement (21 USC 321(n)).

National Research Center for Women & Families president Diana Zuckerman told Reuters that FDA could have done more than send a “vague” letter that does not help “patients in any meaningful way...The problem is there are certain people who are unlikely to benefit [from LASIK] and they don't know who they are,” she said.

Instead, the agency should require doctors and clinics to give potential patients a simple, easy-to-understand booklet that lays out all the possible risks, Zuckerman said. FDA spokeswoman Mary Long said the agency has taken additional steps, including updating its Web site and making it easier for people to report problems to FDA. The American Academy of Ophthalmology physicians' group said it appreciated the “reminder” from FDA and would give the letter to its members.

Stryker Cited for Unapproved Device

FDA's Detroit district office said in a May 5 warning letter that an inspection late last year at Stryker's Portage, MI, facility revealed that the company was marketing its Stryker custom cranial implant without having received FDA approval or clearance. The letter said the device was cleared in April 2005 as a nonsterile device, but the district office determined there had been significant changes or modifications in design, components, method of manufacture, or intended use that require submission of a new premarket notification.

The warning letter also said that the company failed to include required information in the report of correction or removal submitted to FDA. Earlier this year, Stryker recalled the cranial implant, saying that there were concerns about its sterility. In recent years, the company has received numerous warning letters for quality violations at various manufacturing plants, and sales representatives have pleaded guilty to off-label marketing violations.

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