February 3, 2009

Distribution of Medical Publications Discussing Off-Label Uses of Drugs and Devices: FDA Issues Final Guidance on Good Reprint Practices for Drug and Device Manufacturers

Holland & Knight Alert
Michael R. Manthei

In one of the final acts of the Bush Administration, the United States Food and Drug Administration (FDA), on January 12, 2009, released its final guidance regarding “Good Reprint Practices.” The Guidance, “Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices,” (74 Fed. Reg. 1694), sets forth the FDA’s current thinking on the best practices for distribution by manufacturers of publications discussing off-label uses of their drugs and devices.

Prior to this Guidance, the FDA attempted to regulate the dissemination of off-label publications through its authority under the Food and Drug Administration Modernization Act (FDAMA). By following the FDA’s rules, manufacturers ensured that distribution of such publications would not be used as evidence of the manufacturer’s intent to market off-label uses of the product. However, this provision of the FDAMA expired in 2006, thus leaving the FDA without any legal authority to regulate distribution of off-label publications. Thereafter, the FDA published draft guidance in early 2008 to express its current thinking on best practices for the distribution of reprints containing off-label information. This Guidance slightly modifies and finalizes the 2008 draft guidance.

Balancing the Desire for the Approval of New Indications With the Need for Information About Unapproved Uses

In the Guidance, the FDA still encourages manufacturers to seek approval and clearance for new indications of drugs and devices, but also recognizes “the important public health and policy justification” of dissemination of publications on unapproved uses. Overall, the Guidance aims to make certain that off-label articles and publications are “truthful and non-misleading.” In order to do so, FDA makes recommendations directed to the following areas:

1) the types of publications that should be distributed

2) the types of studies and data that it views as sufficient to support such publications

3) the manner in which the manufacturer disseminates the publication to health care professionals

As an incentive for compliance, the Guidance acts as a “safe harbor,” whereby a compliant manufacturer’s dissemination of publications discussing off-label uses will not be used as evidence of an intent to promote off-label use of the manufacturer’s product.

1) The Types of Publications

The Guidance first addresses the types of publications that manufacturers may distribute without evidencing off-label promotion. In order to meet the “safe harbor,” publications must meet all of the following guidelines:

  • be published by an organization that has an editorial board that uses independent experts in the given field to review, select and provide comments about proposed articles, and that adheres to a stated policy requiring full disclosure of conflicts of interest
  • be peer-reviewed and published in accordance with peer-review procedures
  • be generally available through independent distribution channels where medical textbooks and periodicals are sold
  • not be funded by, primarily distributed by, or written or edited by (or at the request of) the manufacturer of the product that is the subject of the article
  • not be edited or significantly influenced by a drug or device manufacturer or by any individuals having a financial relationship with these manufacturers

2) Studies and Data

In addition, the information on which the publication is based must comply as follows:

  • reflect adequate, well-controlled, and scientifically-sound clinical investigations
  • not be false or misleading
  • not pose a significant risk to the public health, if relied upon

3) Manner of Distribution
Finally, the Guidance addresses the manner in which manufacturers should disseminate off-label publications.
All scientific or medical information that is distributed must meet all of the following criteria:

  • be an unabridged copy or reprint that is unmarked and unaltered by the manufacturer
    • be accompanied by: approved labeling; a comprehensive bibliography of publications related to the unapproved use (when such information exists); and a representative publication reaching a contrary or different conclusion regarding the unapproved use (when such information exists)
    • be distributed separately from information that is promotional in nature
    • include a disclosure statement (prominently and permanently affixed to the publication) stating: that the uses described have not been approved or cleared by the FDA; the manufacturer’s interest at stake; any author with a known financial interest in the product or manufacturer, the affiliation of the author, and the nature of the financial interest; any person known to have funded the study; and any significant known risks of the unapproved use that are not discussed in the publication

FDA Focus Is on Disclosure and Clarity

As a whole, the Guidance focuses more on disclosure and clarity of all relevant information than the draft guidance, but is still less stringent than the FDA’s prior review rules under the FDAMA. Given this perceived relaxation of the previous rules, some lawmakers, such as Rep. Henry Waxman (D-CA), strongly opposed the regulation and are encouraging a careful reexamination by the incoming administration.
Holland & Knight’s Health Law and Life Sciences Team attorneys can provide a more detailed analysis of the Guidance as it pertains to your company and its activities, or can assist with incorporating the new guidelines into your compliance program.

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