Off-Label Drug Information

drug into interstate commerce unless the FDA has approved the drug and its label.2 A second provision prohibits manufacturers from introducing misbrandeddrugs into interstate commerce.2 Misbranding is considered to occur if drug labeling contains information that describes unapproved uses or is misleading or insufficient to support safe use for approved indications.2 Materials are considered part of drug labeling when they are distributed by the manufacturer to describe the uses of the drug whether or not they are part of product labeling.2 FDA regulations state that instead of engaging in inappropriate promotion, pharmaceutical companies must submit safety and efficacy data and obtain FDA approval prior to marketing a new drug indication.7 The FDA Modernization Act of 1997 (FDAMA), however, introduced regulations that included a provision (Section 401) that allowed drug and device manufacturers to distribute scientific literature on off-label uses if certain requirements were met (Table 1).2,8 The regulations stated that articles could be distributed only if the off-label use discussed was included in a filed or soon-to-be-filed supplemental New Drug Application (sNDA).2 Companies also had to provide the FDA with advance copies of the materials to be disseminated.2 The articles had to be of high quality, as evidenced by peer review and other specifications.2 If a drug manufacturer was in compliance with all of the requirements, the FDA could not use this activity as proof of a company’s intent to inappropriately promote offlabl drug use.1 Section 401 therefore provided a “safe harbor” for manufacturers with respect to the distribution of journal articles concerning off-label uses.1 The legality of these restrictions in the FDAMA was later questioned in a series of important legal cases that challenged this Act on the grounds that it violated constitutional rights.2 It was argued that the regulatory power granted to the FDA by Congress cannot violate the FirstAmendment right of medical manufacturers to engage in commercial free speech.2 Washington Legal Foundation v. Friedman challenged FDA restrictions on reprint distribution on these grounds.2 In 1999, a federal district court ruled that the objective of the FDA could be met by requiring manufacturers to make clear disclosures regarding the nature of information on off-label uses rather than imposing the restrictions in the FDAMA.2 The FDAMA was subsequently allowed to expire in September 2006.2 On January 13, 2009, the FDA issued new guidance that changed the FDAMA regulations with respect to reprint distribution on off-label uses by manufacturers (see Table 1).2,18 The new guidelines allow companies to distribute peerreviewed scientific articles and texts describing off-labeluses, subject to the new regulations.9 However, the new policy is more permissivethan the FDAMA, because companies are no The author is a Consultant Medical Writer living in New Jersey.