Recently, a “leaked” Food and Drug Administration (FDA) draft guidance document regarding the dissemination of medical journal articles on unapproved uses of approved drug products (i.e., off-label reprints) received considerable media attention 1. It also drew a stern rebuke from Congressman Henry Waxman, who characterized the document as an “ill-advised” attempt to permit, by “administrative fiat,” “far more dissemination of articles on unapproved uses than was [previously] sanctioned[.]”
For the most part, however, the substance of the leaked draft guidance is not new. Most pharmaceutical companies are following many (if not all) of its recommendations. Its real significance, largely overlooked by the media, is that: (1) the document proposes to recognize the role of medical science liaisons (MSLs); and (2) the FDA appears to be working toward an expansion of conduct recognized as “scientific exchange.”
The federal Food, Drug, and Cosmetic Act (FDCA) prohibits a pharmaceutical company, its employees, or agents from promoting an approved drug product for an unapproved use. Until September 2006, the FDCA provided an express safe harbor for the dissemination of off-label reprints under certain circumstances. There remains a judicially fashioned safe harbor under the Washington Legal Foundation line of cases, which hold that the dissemination of medical journal articles, even those regarding off-label uses – but not their use in promotion – merits “the highest degree of Constitutional protection” under the First Amendment 2.
The criteria for disseminating off-label reprints articulated in the leaked draft guidance are consistent with those in the Washington Legal Foundation case law (e.g., the reprint must be peerreviewed, accompanied by the approved labeling for the drug, and distributed separately from promotional information). Moreover, with a few exceptions, 3 the criteria in the draft guidance are also consistent with the now-defunct statutory safe harbor (e.g., the reprint must be accompanied by a prominent disclosure that the uses described have not been approved by FDA).
Recognition of MSLs
To the extent a recipient of a reprint has questions about it, the leaked draft guidance recommends that such questions be referred “to a medical/scientific officer or department, and that the officer or department to which the referral is made be separate from the sales and/or marketing departments 4.” To our knowledge, this would (if the agency were to issue the document) be the first time FDA affirmatively recognized medical science liaisons (MSLs), a type of pharmaceutical company employee that has been used for at least three decades 5. The leaked draft guidance also indicates that FDA may be moving toward sanctioning the use of MSLs in responding in person to unsolicited requests for off-label information regarding a reprint. FDA’s previous guidance suggested that responses to unsolicited requests should be provided in writing.
Dissemination of Reprints at Exhibit Halls
The leaked draft guidance states that “while [off-label] reprints may be distributed at medical or scientific conferences in settings appropriate for scientific exchange, reprints should not be distributed in promotional exhibit halls or during promotional speakers’ programs.” 6 Previously, the only clear examples of scientific exchange we had identified through our work in this area were press releases regarding the results of clinical studies and presentations at scientific meetings. Until the leaked draft guidance became available, there was almost no information about how FDA might interpret the term “scientific exchange” in the regulation governing pre-approval promotion. If issued, the draft guidance would provide welcome -- though still limited -- guidance.