FDA Eases Off-Label Restrictions

The Food and Drug Administration has proposed rules allowing greater flexibility for manufacturers to disseminate information about the safety, effectiveness or benefits of off-label (unapproved) uses for marketed drugs, biologics and medical devices. Under current guidelines physicians are free to prescribe a drug for any condition, but companies may not make claims for these products unless they have been specifically approved by the FDA. The new guidelines cover such information sources as studies published in scientific journals, but only apply to off-label uses which have been, or will be, studied and submitted for FDA approval. The FDA will require that such information be "both reliable and balanced."

When finalized, these rules will implement a provision of the Food and Drug Administration Modernization Act of 1997 (FDAMA), which allows manufacturers to inform physicians, pharmacy benefit managers, health insurers, group health plans and federal and state agencies. The proposed rules, which closely track the FDAMA provisions, specify the type of off-label or unapproved use information that can be disseminated, and under what conditions it must occur. Under FDAMA, the FDA must study its experience with the provision, and the provision will sunset September 30, 2006 or seven years after the final regulation, whichever comes first.

William B. Schultz, FDA Deputy Commissioner for Policy, noted that in the past allowing manufacturers to disseminate off-label information raised concerns about diminishing a manufacturer's incentive actually to develop the safety and efficacy data about these uses that would lead ultimately to a product's approval — concerns addressed by the legislation and implemented in the proposed rules.

"FDAMA and the new proposed rules tie dissemination of this information to a commitment to do the necessary research on the new uses," Schultz said. "These proposed rules are intended to implement the statutory provision which will allow health care practitioners to receive information about unapproved uses of approved medications and devices and to stimulate the development of new studies or collection of existing evidence about off-label uses for FDA's review."

Under the proposal, firms or sponsors no longer would have to wait until the FDA approves their supplemental application before disseminating certain reliable information about unapproved uses of their products, provided the information:

• Concerns a drug or device that has been approved, licensed or cleared for marketing by the FDA
• Is in the form of an unabridged reprint or copy of a peer-reviewed scientific or medical journal article (or an unabridged reference publication) about a clinical investigation considered scientifically sound by qualified experts
• Does not pose a significant risk to the public health
• Is not false or misleading
  
• Is not derived without permission from clinical research conducted by another manufacturer
• Includes certain disclosures (e.g., that the new use has not been approved by the FDA), the official labeling, and a bibliography of other articles relating to the new use.

The manufacturer also would have to submit to the FDA, 60 days prior to dissemination, a copy of the information to be disseminated and other data specified in the proposal.

A firm that has not submitted a supplemental application for the new use could begin disseminating information if it has:

• Certified that it has completed the necessary studies and that a supplemental application will be submitted within six months
• Provided an adequate protocol and reasonable schedule for the necessary studies and certified that the application will be submitted within 36 months of the initial dissemination
• Received an exemption from the requirement to submit an application on the grounds that the necessary studies would be unethical or economically prohibitive.

If the FDA determines that the information is not objective and balanced, it can require the manufacturer to include additional objective and scientifically sound information, or an objective statement prepared by the FDA about the safety or effectiveness of the new use.

Manufacturers would have an ongoing responsibility to provide the FDA with additional information about the disseminated new uses, and the FDA could order the cessation of the dissemination if the additional information indicated that the "off-label" use may not be effective or may pose a significant risk to public health.

Written comments on the proposal, which will soon be published in the Federal Register, should be sent during the next 45 days to:

Dockets Management Branch (HFA-305), Food and Drug Administration, 12420 Parklawn Drive, Room 1-23, Rockville MD 20857.