On January 13, 2009, the Food and Drug Administration (FDA) issued a notice in the Federal Register regarding the availability of its guidance for industry on the distribution of medical journal articles and scientific publications regarding unapproved new uses (also known as off-label uses) of approved drugs. The guidance seemingly creates a safe harbor for dissemination of information on off-label uses of FDA-approved drugs. First, this report outlines the relevant provisions of the Federal Food, Drug, and Cosmetic Act (FFDCA) and related regulations that have been used to address misbranding violations of the act that relate to pharmaceutical manufacturers' promotion of off-label use. Second, the report summarizes the FDA's previous off-label marketing provisions under FDAMA § 401, which are no longer in effect. Third, the report details the January 2009 guidance document and its similarities to and differences from the FDAMA provisions. Fourth, the report outlines First Amendment challenges to FDAMA and older FDA guidance documents addressing off-label promotion. Fifth, the report discusses the nature of guidance documents, in contrast to rules promulgated under the Administrative Procedure Act (APA), as well as administrative law issues associated with the FDA's issuance of the guidance. Sixth, the report provides an overview of the False Claims Act (FCA) and related qui tam cases that addressed off-label marketing practices of pharmaceutical companies. Finally, the report analyzes the interaction of the new guidance document and the FCA. When a person submits a new drug application to the FDA for approval, the application includes samples of the proposed labeling for the drug. While a physician may prescribe a drug for off-label uses, a pharmaceutical manufacturer may not market or promote a drug for uses other than those on the label—those uses approved by the FDA in a drug application. Manufacturer marketing and promotion of off-label uses is linked to the FFDCA's prohibition against misbranding. The guidance does not include the following, which were present in FDAMA: (1) the requirement for a submission of a supplemental new drug application or the Secretary's approval of an application for an exemption from this requirement; (2) the Secretary's ability to require a manufacturer to disseminate (a) additional scientifically sound information to provide objectivity and balance, and (b) a statement from the Secretary on the safety and effectiveness of the unapproved use; (3) the Secretary's ability to order the manufacturer to cease dissemination of information in certain situations, such as if the Secretary determined that the unapproved use may not be effective or may present a significant risk to public health, or if the information did not comply with FDAMA's provisions; (4) provisions that required manufacturers to submit lists of the articles and reference publications that they disseminated and to keep records in case the manufacturer was required to take corrective action; (5) the requirement that the manufacturer include, along with the information being disseminated, "a statement that there are products or treatments that have been approved or cleared for the use that is the subject of the information being disseminated" and, if applicable, a statement "that the information is being distributed at the expense of the manufacturer"; (6) the requirement that a copy of the information to be disseminated and clinical trial information regarding the unapproved use be submitted to the Secretary 60 days prior to dissemination; (7) the requirement that the article not have unapproved uses of drugs or devices as its primary focus; and (8) a provision requiring that a scientific or medical journal be a publication "that is generally recognized to be of national scope and reputation." The FDA appealed. Nor would the FDA's guidance affect the legal authority, enforcement powers, or other capabilities of outside agencies that have been involved in prosecuting FCA cases related to off-label marketing, such as the HHS Office of Inspector General, the Federal Bureau of Investigation, and the Department of Justice.
New drugs may not be introduced or marketed without the approval of the Food and Drug Administration (FDA). When a person submits a drug application to the FDA for approval, the application includes samples of the proposed labeling. The FDA may refuse to approve an application if the drug is not safe or effective for the specific uses that are reflected in its labeling. An unapproved new use of a drug, also known as an off-label use, is a use not mentioned in the drug's approved labeling. Although a physician may prescribe a drug for off-label uses, a pharmaceutical manufacturer may not market or promote uses of a drug other than those on the label—those uses approved by the FDA in the application.
In January 2009, the FDA issued a guidance document on the dissemination of medical information regarding off-label uses of drugs. The guidance seemingly creates a safe harbor for dissemination of information on off-label uses of FDA-approved drugs and medical devices. However, the agency's guidance statement does not have the force or effect of law, and the FDA still retains its legal authority under the Federal Food, Drug, and Cosmetic Act (FFDCA) and FDA regulations to determine when promotion of an unapproved new use has occurred or when a product is misbranded. Additionally, the guidance does not affect the legal authority, enforcement powers, or other capabilities of outside entities that have been involved in prosecuting False Claims Act (FCA) cases related to off-label marketing and the submission of false claims for reimbursement from the U.S. government.
First, this report outlines the relevant provisions of the FFDCA and related regulations that have been used to address misbranding violations of the act that relate to pharmaceutical manufacturers' promotion of off-label use. Second, the report summarizes the FDA's previous off-label marketing provisions under the FDA Modernization Act of 1997 (FDAMA), which are no longer in effect. Third, the report details the January 2009 guidance document and its similarities to and differences from the FDAMA provisions. Fourth, the report outlines First Amendment challenges to FDAMA and older FDA guidance documents addressing off-label promotion. Fifth, the report discusses the nature of guidance documents, in contrast to rules promulgated under the Administrative Procedure Act (APA), as well as administrative law issues associated with the FDA's issuance of the guidance. Sixth, the report provides an overview of the FCA and related qui tam cases that addressed off-label marketing practices of pharmaceutical companies. Finally, the report analyzes the interaction of the new guidance document and the FCA.