Industry Welcomes Guidance on Off-Label Use

NEWS TRENDS

A draft guidance outlining how companies can distribute journal articles that discuss unapproved uses of FDA-approved devices is being greeted with open arms.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.

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