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On Friday FDA issued a draft guidance that would allow device companies to distribute articles from medical and scientific journals that discuss unapproved uses of medical devices. The “Good Reprint Practices” document has suggestions companies should follow when giving out journal reprints and other reference materials. Guidelines include that the article be peer-reviewed and published by an organization that has an editorial board, and that there’s full disclosure of conflicts of interest. The guidance also recommends against distributing materials that have been funded by one or more of the manufacturers of the products in the article. FDA is currently seeking public comments on the draft guidance.

– From MD&DI’s blog.

Saying that he has lost confidence in FDA Commissioner Andrew von Eschenbach and other top FDA officials, Congressman Bart Stupak (D-MI) has called on von Eschenbach to resign, reports the Associated Press. Stupak, chair of an investigative panel charged with FDA oversight, believes FDA approved the antiobiotic Ketek despite knowing that a safety study of the drug had faulty data. Von Eschenbach told the panel last year that that study was not used in determining whether to approve the drug. Stupak now wants to know whether von Eschenbach committed perjury, and is seeking the commissioner’s notes from that appearance. HHS Secretary Michael Levitt has declined to turn them over so far. Stupak said he also lost confidence in FDA after it failed to inspect a Chinese plant that has been linked to manufacturing problems with a blood thinner.

While the controversy has nothing to do with medical devices, industry should expect Stupak and his allies in Congress to be similarly aggressive the next time a problem with a device hits the headlines. They smell blood.

– Erik Swain

The FDA Amendments Act of 2007 (FDAAA) includes several important changes to regulation, particularly regarding user fees, medical device reporting, and registration and listings. But the most important changes — regarding amendments to clinical trial registries — may not be getting the recognition they deserve, says a prominent lawyer.

FDAAA dramatically expands the clinical trials database maintained by the National Institutes of Health, said Jeff Gibbs, a director at the law firm of Hyman, Phelps & McNamara, P.C. The database now includes all medical devices, which was not the case before. Gibbs spoke at a conference put on by his firm on Feb. 8.

Either failing to report a trial to NIH or submitting a false or misleading certification can now lead to civil money penalties of up to $10,000 per proceeding for medical device companies, he said. Furthermore, failure to correct a violation within 30 days after receiving notice of it could result in a fine of $10,000 per day.

Therefore, he said, device makers must carefully study these new requirements. And because no guidelines on this topic are available yet, the only way for device companies to protect themselves is to create a Standard Operating Procedure. “This is completely new, and it is public,” Gibbs said. “You must have a procedure in effect, and you must implement it immediately.”

– Heather Thompson

Unless substantial resources are provided to improve FDA’s workforce, the safety of products regulated by the agency could be in jeopardy. A yearlong evaluation of the scientific and technological capacities at FDA found deficiencies in the regulatory systems that oversee medical devices, drugs, cosmetics, and food.The work was initiated at the request of FDA commissioner Andrew von Eschenbach. He asked FDA’s Science Board to form a subcommittee to review whether science and technology at FDA could support current and future regulatory requirements. What they found might not have been a surprise to those who work at the agency. However, the findings alarmed the members of the Science and Technology Subcommittee, which released a 300-page report in December.

“I don’t think it’s news to FDA that [it] needs more resources,” says Thomas Novelli, director of federal affairs at the Medical Device Manufacturers Association (MDMA). “I think internally they’re always saying ‘we need more resources and more appropriation.’ The administration isn’t necessarily meeting those demands, at least in its budget proposals. Congress, for its part, hasn’t been meeting those demands either.”

The report states that FDA has “serious scientific deficiencies” that render the agency unable to meet regulatory responsibilities. According to the report, the deficit comes from high demand on FDA resources and the lack of increased capital to meet the need. Products are becoming more innovative and complex. There is pressure from the public and Congress to do more about safety issues. Yet, the resources the agency is getting aren’t proportional to those expectations. “Today, not only can the agency not lead, it cannot even keep up with the advances in science,” the report says.

The subcommittee wants to see significant changes within FDA, including the establishment of a chief scientific officer, the development of incubators for innovation, which would increase networking between universities and industry, and the improvement of information technology (IT) and data analysis.

The subcommittee consists of three members of the Science Board and 30 additional experts in regulatory science, including leaders from industry, academia, and other government agencies. Some of them said during a media conference call that Congress has the power to correct the lack of resources within FDA. They documented that, in the last 20 years, Congress has enacted more than 125 separate statutes requiring FDA to carry out various actions and programs, while providing the agency with just 817 new employees.

“Only Congress can provide the money and people needed to restore FDA science to the level necessary to implement its statutory obligations to protect the public health,” says Peter Barton Hutt, senior counsel at Covington and Burling LLP (Washington, DC). “Unless Congress appropriates additional money and personnel, none of the recommendations of our subcommittee can possibly be implemented.” Hutt is a former chief counsel for FDA.

The main problem areas cited in the report are a weak scientific organizational structure, major gaps in scientific expertise, and an inadequate IT infrastructure, which the subcommittee called disturbing. In addition to recruitment challenges, the turnover rate of the science staff is double that of other government agencies.

“We have insufficient IT expertise to support emerging sciences such as genomics, nanotechnology, and wireless devices,” says Dale Nordenberg, MD, managing director of healthcare industry advisory at PriceWaterhouse­Coopers LLC (Atlanta). “This means that FDA can’t effectively support innovation in the industries that it regulates.” The shortcomings could also affect the nation’s global competitiveness, he says.

Nordenberg adds that clinical trial data are trapped in piles of warehouse paper, which prevents valuable analysis from helping people. According to the report, there are no backups of such records either. FDA’s computer systems and networks are also out-of-date and cannot keep up with evolving science. “We’ve seen an IT infrastructure [that] can’t support the growing regulatory burden caused by globalization, including the need to monitor 300,000 sites globally,” Nordenberg explains.

The report asserts that increased funding is critical for FDA to get the resources it needs. However, the question remains whether such funding would be sufficient.

MDMA and AdvaMed are working with an advocacy group, the Alliance for a Stronger FDA, to push for an increase in agency resources. The group was formed after the merger of two similar organizations, the FDA Alliance and the Coalition for a Stronger FDA.

“AdvaMed believes FDA must be given adequate resources so that it can continue its vital work of protecting and promoting the public health,” says Janet Trunzo, executive vice president of technology and regulatory affairs at AdvaMed. “The Coalition [for a Stronger FDA] is committed to working with the administration and Congress to ensure that FDA has the resources it needs to meet its mission.”

Unfortunately, there is also a disparity between FDA’s budget and that of other government agencies. For example, FDA’s annual IT budget is about $200 million, whereas the yearly IT budget at the Centers for Disease Control is $500 million. “When you consider the regulatory mandate of FDA, and the impact on industry as well as on medical products and consumer safety, it seems reasonable that the IT budget for FDA needs to be increased substantially.” Nordenberg estimates that the IT budget needs to be increased by 100–150%.

External subcommittee adviser Roy Vagelos suggests a yearly plan to bring in new leadership, build statistics, and develop an extension of resources, which he thinks should be doubled over a five-year period.

Steven Grossman, executive director of the Alliance for a Stronger FDA, says the coalition discussed a 15% budget increase, which probably won’t be enough. “We believe the size and magnitude of the needs range from $250 million to $450 million a year, and you’re looking at four to six years to accomplish all that needs to be done at that level.”

The subcommittee’s report, FDA Science and Mission at Risk, is available on FDA’s Web site.

– Maria Fontanazza

FDA’s authority to investigate itself when employee misconduct is alleged was rescinded in November when the HHS Office of the Inspector General (OIG) reclaimed that authority. However, Roland Jankelson quickly told the House Energy and Commerce leadership that this step may not be enough to prevent continuing abuses. He cited alleged CDRH abuse of TMJ Implants (TMJI; Golden, CO) and his own company, Myotronics Inc. (Kent, WA), in 1997.

OIG improperly abandoned a strong case it had built several years ago against CDRH employees in the TMJI matter, Jankelson wrote in a letter to committee chairman John Dingell (D–MI) and Subcommittee on Oversight and Investigations chairman Bart Stupak (D–MI).

OIG had been “presented with compelling evidence of multiple abuses—[including] conflicts of interest and manipulation of the premarket approval [PMA] process to assure a desired outcome,” Jankelson wrote. He said this abuse included the “manipulation and stacking of a review panel and treating TMJI’s PMA review with different (harsher) standards than the review of another company favored by the lead reviewer.” OIG’s investigator, Matthew Kochanski, informed Jankelson on several occasions “that the investigation was nearly complete and would provide findings of criminal wrongdoing,” but then Jankelson was no longer able to make contact with Kochanski and “no results were ever made public. Someone had the capability to ‘bury’ these findings from ever being revealed.” Kochanski is no longer listed in the HHS employee directory.

“Hopefully,” Jankelson’s letter concluded, “the Office of the Inspector General will not be allowed to be just another level of bureaucracy behind which misbehaving FDA employees can hide.”

– James G. Dickinson

After quietly implementing a new method for analyzing software, FDA’s Software Forensic Laboratory was able to find some problems in a couple of high-profile devices that were recalled for adverse events. Called static code analysis, the technique is commonly used in the automotive and aeronautical industries and has been around for about 10 years. Simply put, it reads the lines of code without running the program. It is designed to check for errors that might keep the code from running correctly. It has been used extensively in aeronautics, and it is seen as essential in that safety-critical industry. Sounds ideal for the medical industry, right? Or, maybe not. It is costly and labor intensive—both of which can be impediments for the medical device industry.FDA consulted with other federal agencies that deal with software integrity issues—including the Department of Defense, FBI, National Institute of Standards and Technology, and NASA—before it started using this technique, which was outlined in a single paragraph in the 2006 CDRH annual report. The agency determined that such analysis would be particularly valuable in understanding the root causes of adverse events due to software failures. Whether this a good investment of FDA’s regulatory enforcement budget remains to be seen.

Often, the result of this analysis is an itemized list of coding errors that is sent back to the manufacturers. The list can contain any error, from minor misspellings or typos to major errors. But the list does not prioritize the code errors, and OEMs are expected to respond to all items.

FDA says it is currently reviewing only software that presents “an imminent public health threat.” According to MedSun, the FDA laboratory has used the new method with success to analyze software in several high-profile compliance cases. It is clear that the agency is expecting to find errors in the software that the manufacturers themselves have overlooked.

However, FDA has also said that it expects manufacturers to “increasingly” use such tools during their product development process. FDA generally avoids prescribing specific methods to industry. Does this expectation mean that FDA is advising manufacturers on how to design their software?

Some designers are already using this technique in the development of their software. Full Spectrum Software (FSS; Framingham, MA) uses both static and runtime analysis. “This is a part of our quality system, and the results are clearly and demonstrably beneficial,” says Andrew Dallas, president of FSS. “We provide a service called product hardening, which allows us to improve overall product stability and reliability.” The components include not only static and runtime analysis, but also manual code review.”

As a design tool, it is important to recognize that static analysis does not just find insignificant errors. These processes actually find coding errors created by the software engineers, explains Dallas. “The types of errors we can find are much more profound than spelling errors,” he says. “Consider a product that is designed to run for 12 hours and is acquiring patient information during that time. If a programmer has failed to initialize a variable, the value within that variable can be any value.”

He says that a major error can occur if the code uses that variable to make a decision: “If x is zero, shut down.” Static and runtime analyses can find such errors as well as others that are potentially even more serious. “Really the only downsides of the hardening process are cost and time,” he says. “These downsides, however, are quickly recouped in reduced maintenance costs.”

Static analysis can be a good tool when used at the design stage. And if you do, it may keep you from ending up in FDA’s forensic laboratory after an adverse event. FDA expects manufacturers to adopt this method of analysis, but it has not specified a timeline.

Perhaps FDA’s decision to do such analysis will also have some unintended consequences. It would be a tragedy if manufacturers cut back on validation activity in favor of waiting to simply respond to FDA’s itemized list of coding errors.

– Sherrie Conroy

President Bush has proposed a $2.4 billion budget for FDA in fiscal year 2009, a 5.7% increase over the current year. That figure includes funds from user fees; without it, the budget comes to $1.77 billion. It includes additional funds targeted at improving the safety of medical devices and other FDA-regulated products, and implements programs to be funded by user fees as per the FDA Amendments Act of 2007.

But is it enough? Some think not. The Alliance for a Stronger FDA recommends that Congress appropriate $2.1 billion instead of $1.77 billion. An alliance spokesman said that the appropriation is “barely half” of what the agency needs just to keep up with inflation. (The alliance was formed from a merger of two groups, the FDA Alliance and the Coalition for a Stronger FDA.)

FDA’s responsibilities have increased dramatically over the past 20 years, but its funding has not kept up at the same pace. The government is faced with a choice: Either give the agency the money it needs to perform its mission, or scale back its mission. Perhaps some combination of both is warranted.

– from MD&DI’s blog.