Diagnostics & Imaging Week Executive Editor

The line between providing information about a healthcare product and promoting and marketing that product is a fine one.

But the FDA appears to be moving that line in a way that could expand greater off-label uses of drugs and devices by doctors – and better yet, the agency says, lead to well-informed use of these off-label applications. (And the guidance could provide a boon of no small size to those providing printing services to these companies.)

The agency has issued a draft guidance defining the type of information that a company can provide to physicians – essentially reprints of articles concerning the unapproved, off-label uses of a product, but specifically concerning a product that has received FDA approval for one more uses.

The draft guidance on “Good Reprint Practices” supports the use of “medical or scientific journal articles and reference publications” providing information concerning these unapproved uses.

The FDA has long attempted to warn companies against the marketing of unapproved uses of drugs and devices, and it says that the new guidance does not allow broader marketing and promotion, but specifically warns against it.

Randall Lutter, FDA deputy commissioner for policy at FDA, in an agency statement, said that dissemination of information concerning unapproved uses of drugs and devices “can contribute to the practice of medicine and may even constitute a medically recognized standard of care.”

And he said that the guidance “safeguards against off-label promotion.”

The guidance supplants guidelines concerning the dissemination of information on unapproved uses of FDA-approved products that expired in September of 2006, thus probably leaving companies considerably unsure as to what the agency’s current stance is.

In the draft guidance, the FDA says that its policy on this matter “has not changed” – though several reports about the document have indicated that it is expanding or “softening” the use of information concerning unapproved uses.

And the newly issued draft guidance has come under fire as providing too much leeway to manufacturers because tending to encourage marketing of these unapproved uses.

Representative Henry Waxman (D-California) – he of the recent grilling of Major League Baseball’s Roger Clemens – had written to the agency, asking it to delay issuance of the guidance, arguing that it would create a “large loophole” in the law against off-label promotion.

“It’s a conflict of interest for the company to be promoting sales when they haven’t been able to establish that a drug is safe and effective through the rigorous FDA process,” Waxman said.

The guidelines were published in yesterday’s Federal Register, and the agency is accepting comments on it for 60 days.

Importantly, the draft guidance emphasizes that “marketing” of an unapproved use constitutes misbranding and adulteration of that product. And it provides considerable detail concerning:

• the kinds of materials that can be provided to physicians;

• the format of these materials;

• and the “manner” of dissemination.

Concerning the types of materials: they should come from organizations with editorial boards and be peer-reviewed, rather than being distributed or in any way influenced by the product manufacturer. And the information should constitute “the weight of credible evidence derived from adequate and well-controlled investigations.”

The format of these materials should be essentially unaltered reprints and not be abridged, “marked, highlighted, summarized, or characterized by the manufacturer in anyway.
And the information should be accompanied by other supplementary information, as follows:

• the approved labeling of the drug or device;

• “a comprehensive bibliography” of publications covering similar uses of the drug or device”;

• and any contradictory information about the use of the drug or device if contrary conclusions about the off-label use have been published elsewhere.

In addition, the draft guidance recommends against distribution of special supplements or publications that have been funded by one or more of the manufacturers of the product in the article.

The guidance says that there are “important public policy reasons for allowing manufacturers to disseminate truthful and non-misleading journal articles and medical or scientific reference publications on unapproved uses” of approved products.

“These off-label uses,” it says, “may be important and may even constitute a medically recognized standard of care” as long as the information provided concerning these uses is “truthful and not misleading.”