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FDA Commissioner Andrew von Eschenbach says that it is misleading to get caught up in the numbers when it comes to assessing how often foreign device and drug plants that make products for the United States should be inspected. He told Bloomberg Television that foreign inspections should be risk-based, just like domestic inspections are. That means plants that make high-risk devices or have a history of noncompliance could be inspected more than once every two years, while plants that make lower-risk devices and have good compliance records could be inspected at a less frequent rate.

Also importantly, he said FDA needs to share data with other countries to help each agency determine which plants are in most need of frequent inspection. He especially envisions such collaboration in countries like China, which have immature regulatory systems.

The Government Accountability Office says FDA’s plans to boost foreign inspections of drug and device plans don’t go far enough, reports the Star-Ledger of Newark, NJ. Congressional Democrats agree, and two of the party’s leaders in the House chided FDA Commissioner Andrew von Eschenbach for not doing enough to fix a system that led to, among other things, contaminated heparin from China reaching U.S. shores.

The GAO said it would take $67-71 million per year to inspect just the foreign drug plants that make products for the U.S. in a timely manner — never mind medical device and food plants – but FDA has only committed $11 million for all foreign inspections this year, and $13 million next year.

von Eschenbach said he has asked for more money to conduct foreign inspections, but did not say how much. He added that increasing inspections will not solve the problem by itself. “I don’t believe that’s the solution to the problem,” he told Congress. “It’s much more complex, and the solution needs to be much more comprehensive than simply inspecting a facility. I believe we are making progress, but the problems are substantial, and they require substantial effort.”

A bill proposed in the House of Representatives would require all medical devices being imported into the United States to be labeled with their country of origin, reports the Associated Press. The bill would also create a permanent foreign-inspection staff for FDA and mandate that overseas device and drug plants be inspected every two years. These measures are spurred by a slew of recent reports about tainted products from China, including a recall of heparin, which is used as a medical device coating.

Also of significance is that the bill contains language that gives FDA the power to force recalls. Currently, they can only suggest that a manufacturer conduct a recall. The vast majority of the time, the manufacturer complies.

– From MD&DI’s blog.

A draft guidance outlining how companies can distribute journal articles that discuss unapproved uses of FDA-approved devices is being greeted with open arms. It marks the first time that the agency has considered allowing manufacturers to mention off-label uses to physicians in any way.

FDA’s Good Reprint Practices document suggests how device firms should disseminate scientific or medical journal articles and reference materials that talk about off-label device use.

“It’s significant because it shows that FDA recognizes there’s a legitimate zone of communication between manufacturers and the healthcare industry regarding truthful and nonmisleading materials on off-label uses,” says Pamela Furman, partner at King & Spalding LLP (Washington, DC).

Overall, the proposed guidance has been praised within industry, but opponents have criticized FDA for letting companies promote potentially unsafe, unapproved uses of devices.

In a November 30, 2007, letter to FDA commissioner Andrew von Eschenbach, Congressman Henry Waxman (D–CA) wrote that the “ill-advised” guidance would create a “large loophole in the law and create a pathway by which drug and device manufacturers can promote unapproved uses of their products without first obtaining FDA approval.” (The document was not made public until this February, but Waxman saw an internal version of it last October.)

Although there may be potential for abuse, the draft offers guidelines for the types of acceptable articles and how they should be distributed.

“This is not really a loophole,” says Jonathan Kahan, partner at Hogan & Hartson LLP (Washington, DC). “If you look at FDA’s criteria for disclosing here, it has to be a peer-reviewed journal article or textbook, and there has to be full disclosure that it includes off-label information. Therefore, I think as long as it’s not false and misleading and there is full disclosure, it can actually significantly benefit the patient.”

According to FDA spokeswoman Rita Chappelle, the agency proposed the guidance to clarify its current thinking on what constitutes a good reprint. The guidance on reprints was contained within section 401 of the FDA Modernization Act of 1997, which expired in September 2006.

“By issuing this guidance, FDA hopes to clear up any confusion about our thoughts on this and also hopes to provide guidance on what would constitute a safe harbor from current laws,” says Chappelle. Further, she explains, it enables FDA to begin enforcement action against firms that operate outside of the principles laid out in the guidance. Chappelle adds that the agency retains the legal authority to decide whether the distribution of material promotes an unapproved new use or whether such actions cause a product to be considered misbranded or adulterated.

“The guidance is not an open season to spread off-label information. It’s very specific to truthful, educational information,” says Robert Klepinski, an attorney at Fredrikson & Byron P.A. (Minneapolis). He explains that in releasing the guidance, FDA has acted pragmatically and recognized the state of the law.

In addition to being peer reviewed, articles must reveal any conflicts of interest and must be published by an organization that has an editorial board. The draft recommends against distributing materials that have been funded by manufacturers of the product in the article.

Doctors and other users now have instant access to articles via Internet. Kahan says that it’s valid for companies to provide truthful and correct documents about off-label device uses when approached by doctors. “Not only should the company be able to do that, they probably [also] have an obligation, so that the doctor fully understands from the journal article what’s being done and how the device is being used.”

To adhere to the guidance, companies should employ a standard operating procedure (SOP) to help train employees, Klepinski advises. “People are going to need an SOP to control how they train the sales force in how to follow this guidance and the in-house employees in executing it.”

Klepinski’s only criticism of the draft is the labeling recommendations, which are supposed to accompany the journal reprint or reference material. He says the labeling section is either too vague or too detailed, depending on the recommendation.

Furman also feels that more clarification is needed. For example, she says, FDA requires a disclaimer or disclosure attached to any materials for which there is a risk or safety concern posed by any unapproved use that is significant and known to the manufacturer. “I think that’s a subjective notion and can sometimes be a tough call,” Furman says.

Klepinski agrees, adding that it puts a big burden on manufacturers. “The purpose of these articles is to tell one doctor what another doctor is doing. The manufacturer isn’t going to know, by definition, all of the risks—they haven’t done this research.”

Furman and Klepinski expect other stakeholders in industry to express concern over the labeling issues as well. FDA is accepting public comments on the draft guidance until April 21. A copy of the document is available on FDA’s Web site.

– Maria Fontanazza

FDA is making a pitch to the U.S. Sentencing Commission for more-stringent maximum sentences. The commission is considering new sentencing guidelines.In February, FDA assistant commissioner for accountability and integrity William McConagha told the Sentencing Commission that it should determine the adequacy of the existing guidelines for the Federal Food, Drug, and Cosmetic Act (FD&C Act), which covers medical devices.

“We at FDA believe that establishing an appropriate penalty framework for violations of…[the FD&C Act] is critical to provide a specific and general deterrent to crimes that threaten…the public health,” McConagha testified. “For that reason, we believe that realistic sentencing guidelines for these offenses are of vital importance to the agency’s public health mission.”

He said that the current guidelines are inadequate to address the significant public health consequences of various FD&C Act offenses. Most FD&C Act offenses, he said, involved adulterated or misbranded products.

Products, he said, can be adulterated or misbranded for many reasons set forth in the FD&C Act. The existing sentencing guidelines don’t directly address whether misbranded or adulterated FDA-regulated products can be viewed as having value when loss is calculated. So McConagha suggested revising the guidelines to provide that, in those cases, loss would include the amount paid for the product with no credit for a product’s purported value.

That proposal drew fire from attorneys at the Washington, DC–based law firm of Hyman, Phelps & McNamara, who said it “raises many questions and concerns. First, creative lawyers in the context of civil litigation may try to employ FDA’s proposed finding to seek a monetary recovery based on that
calculation.

“Second, the change would almost certainly dramatically increase sen-tences to be imposed in cases where loss is at issue, including all felony cases.

“Third, if adopted, it may make it very difficult for companies and individuals to work out guilty pleas with the government because the guidelines will warrant a sentence that the defense will find intolerable.”

The firm’s FDA law blog says FDA’s position is “breathtaking in its scope.” The attorneys note that every day, many manufacturers distribute products that are not in full compliance with all FD&C Act mandates and thus are technically adulterated and misbranded. Such distribution routinely occurs with FDA’s knowledge, the blog says. To say that all adulterated and misbranded products are worthless “raises serious legal and policy issues that the commission should fully explore before adopting FDA’s suggestion.”

John Fleder, a director in the law practice, said there is “no evidence that the system is broken or that the proposed changes…are necessary or appropriate based on the FD&C Act statutory scheme, the purposes of the guidelines, or the actual record of FD&C Act criminal enforcement.”

– James G. Dickinson

In case you were wondering whether FDA was going to learn from its loss in court to Utah Medical, the answer is apparently no.

Just as with three previous agency defeats in federal court, the Utah Medical case has been omitted from The Enforcement Story, the agency’s official public report of significant legal decisions, which is published annually by the Office of Regulatory Affairs (ORA).

The Utah Medical case is legally significant because it established that, in quality system regulation or GMP compliance, a medical device company is free to depart from the prescriptive direction of FDA officials—that “many roads lead to Rome.” In other words, government enforcement of penalties requires officials to identify which Code of Federal Regulations requirements are being violated by a device firm, not dictate methods that a company must use to comply with those regulations.

In normal circumstances, such guidance from the federal judiciary could lead to a change in agency practices. The current practice is one of prescribing “how to” advice to industry, through workshops, speeches, informal advice, interpretive guidances, and other means, as opposed to “what to” advice.

However, shortly after the Utah Medical decision was handed down, a senior FDA attorney was reputed to have said, informally among other lawyers, that the decision was delivered by an “aberrant” judge. (Utah Medical judge Bruce S. Jenkins, who was appointed by President Carter in 1978, actually has a long list of home-state accolades and honors to his credit.)

Since then, no FDA or Department of Justice attorney associated with the case, or any other federal official, has been willing to discuss the case, either on or off the record. Because most professional legal forums in what is known as the “FDA bar” rely heavily on the fraternal participation of FDA attorneys, that reliance effectively discourages anyone from discussing this case in formal programs. It’s as if it has simply vanished.

When I reported on Jenkins’s record in January on FDAweb.com, it attracted a sneering anonymous comment from someone who seemed to be familiar with the case from FDA’s perspective. “These plaudits all come from the judge’s alma mater or the Utah [State] Bar. Utah is well known as a rogue state with uber-libertarian sentiments regarding federal regulation of any kind, and that sentiment is even more prevalent in the realm of drug, device, and dietary supplement regulation.”

Two separate requests for an explanation for the omission from ORA’s most responsible officer, associate commissioner for regulatory affairs Margaret O’K. Glavin, garnered no response.

Apparently, in FDA’s mind, this “aberrant” and inconvenient truth never was.

In an agency over which commissioners may reign but not rule, as reported last month, why should we be surprised if, below these nominal commissioners, subordinates may overrule the orders of judges?

– James G. Dickinson

Members of a Senate appropriations subcommittee yesterday declared that FDA needs a significant increase in funding in order to accomplish its mission, and asked FDA Commissioner Andrew von Eschenbach to estimate how much of an increase the agency could absorb without logistical problems, reports the New York Times. After the Senate passed a resolution calling for a 20% increase in FDA’s budget, von Eschenbach said the agency would have trouble absorbing that much of an increase in one year. So Sens. Herb Kohl (D-WI) and Robert Bennett (R-UT) asked him to estimate how much the agency could absorb in one year. He said he would be happy to present them with a series of options at a later date. He also said he wants to hire about 700 people next year, but would not be able to do so if President Bush’s budget proposal were adopted unchanged.

The commissioner sounded more optimistic about the agency’s ability to accomplish his mission than he had previously, however. In a speech last month, he said that FDA may fail in its mission because of funding. Yesterday, he said that FDA remains the gold standard of food, drug, and device regulation, but that it must change if it wants to maintain that level.

– From MD&DI’s blog.

HHS Secretary Mike Leavitt said FDA plans to open an office in China to better get a handle on contaminated medical devices, drugs, foods, and other products being exported from that country, the Associated Press reports. The agency expects to begin work there next month, with the official office opening coming in October.

This signifies a change in strategy for the agency, which had been trying to detect unsafe products during customs. That’s no longer feasible, Leavitt said, because it is impossible to inspect all of the massive numbers of imported products. So now, he said, FDA’s strategy will be to work with Chinese regulators to “build safety into the products.” Similar arrangements with India and some Central American countries could come soon.

The FDA office in China will be headed by Christopher Hickey, director of the HHS Asia/Pacific office.

– From MD&DI’s blog.

In the wake of some high-profile recalls of drugs and devices and the bad publicity FDA received from them, the FDA Amendments Act included the creation of a new position, Chief Scientist. The agency has now filled that position with Frank M. Torti, MD, MPh.

Torti will coordinate the FDA Fellowship Program, which will recruit up to 2,000 professionals of varying disciplines for a two-year training program. And his office will work to ensure the quality and regulatory focus of the intramural research programs of the agency. A cancer researcher, Torti had been working at the Wake Forest University School of Medicine.

The recent problems underscored how much the agency’s scientific knowledge is lacking, and how much trouble it is having keeping up with new developments in medical science and technology. Whatever Torti can do to help improve those things will be greatly appreciated.

In his “Andy’s Take” column on FDA’s Web site, FDA Commissioner Andrew von Eschenbach says he sees the agency’s new draft guidance on testing for drug-eluting stents as a preview of the kind of collaboration the agency will need in the future. The guidance “not only emphasizes the value of collaboration within FDA, but more importantly, it previews the future challenge of regulating medical products that are not only combined, but are truly integrated in their function,” he wrote.

FDA has to get better at this, he said. Nanotechnology products will make this kind of analysis and collaboration essential. But, he cautions, “regulatory agencies like FDA are not aligned for this new reality and I believe we must change just as the products are changing. FDA must work in an interdisciplinary and coordinated way to create a well-defined regulatory pathway that enables us to assure the benefits and risks that are associated with each element in these products as well as with the entire product itself.”

This is quite true. But the question is, will the rank-and-file go along with it?