FDA Guidance on Unsolicited Requests for Off-Label Information

San Francisco—During a Contemporary Issues session at the AMCP meeting, representatives from the FDA Office of Prescription Drug Promotion (OPDP) and the industry reviewed the FDA’s official Guidance for Industry on responding to unsolicited requests for off-label information about prescription drugs and medical devices.

Elaine Hu Cunningham, PharmD, a senior regulatory review officer with the FDA, began the presentation by defining the limitations on prescription drug promotion that have been determined by the FDA, noting that “statements that promote a drug or device for uses other than those approved or cleared by the FDA may be used as evidence of a new intended use.” While these limitations have been set, the FDA recognizes that healthcare professionals can usually use FDA-approved products for treatment indications outside of the approved labeling, some off-label uses provide therapeutic value to some patients, and some off-label information may be useful to individuals seeking information about a medical product.

To address off-label use, the FDA is providing recommendations for communicating nonpromotional information. Specific guidance will address scientific and educational activities; the distribution of reprints; and commercial responses to unsolicited requests for off-label use information. Dr. Cunningham explained that the draft Guidance for Industry was issued in December 2011, and that the period for comment was open until March 29, 2012. The FDA is now in the process of reviewing comments and revising the draft Guidance based on appropriate comments in preparation for issuing a final Guidance document, according to Dr. Cunningham.

Dr. Cunningham clarified that a new or off-label use according to the draft Guidance was one that is not included in the approved product labeling, or one that is not included in the statement of intended use for a cleared device. She said that this definition includes, but is not limited to, a completely different indication or a modification of an existing indication, including a new dosage; a new dosing schedule; a new route of administration; a different duration of usage; or use in a new age group. Furthermore, she noted that unsolicited requests referred to those initiated by persons or entities that are completely independent of the relevant firm, and not prompted in any way by a manufacturer or its representatives.

Dr. Cunningham offered specific examples of both nonpublic and public unsolicited requests for information. While nonpublic requests are usually initiated through a 1-on-1 communication, a public request for information is made through a public forum. She noted that regardless of whether the request was made through nonpublic or public channels, the FDA’s policy is that a firm choosing to respond to the request “should provide the final response containing the requested off-label information about its product only to the specific individual who requested the information as a private, 1-on-1 communication.”

In responding to nonpublic unsolicited requests, Dr. Cunningham described the FDA’s requirements that the response be provided only to the individual making the request; be tailored to answer only the specific questions asked; be truthful, not misleading, accurate, and balanced; be scientific in nature; and be generated by medical or scientific personnel. She also listed the required paperwork that should accompany responses to unsolicited requests. For public requests, Dr. Cunningham said that the representatives responding to the request should clearly disclose their involvement with the firm, and that the response should not be promotional in nature.

The session continued with a presentation from Iris Tam, PharmD, director, managed care medical communications at Genentech and a member of the AMCP Format Executive Committee, continued the discussion with a review of the AMCP Format for Formulary Submissions and the impact of FDA Guidance on AMCP Format.

Dr. Tam noted that the FDA Guidance on unsolicited requests is highly anticipated by the pharmaceutical and device industry. The FDA Guidance has the potential to impact pharmacy and therapeutics committee and formulary review processes because information from drug manufacturers may be considered in evaluations of drugs and drug classes for coverage and reimbursement decisions, according to Dr. Tam. She highlighted the fact that healthcare decision makers often need information beyond a product’s standard prescribing information when making these formulary decisions.

To address the ongoing need for off-label information during these processes, Dr. Tam explained, “the AMCP Format for Formulary Submissions was created as a template and guideline for product-related information provided by drug companies upon receiving an unsolicited request.” “The AMCP Format provides a consistent means for providing clinical and economic information that demonstrates the value of a product in a clear and transparent manner,” Dr. Tam added. Specifically, the AMCP Format has the 2 stated goals of (1) improving timelines, scope quality, and relevance, and (2) streamlining the evidence acquisition and review process.

Dr. Tam compared the AMCP Format and AMCP eDossier System for unsolicited requests against the FDA draft Guidance, concluding that the AMCP Format seems to align with the FDA draft Guidance. She noted that in discussions with AMCP members, no major concerns have been identified. When the final FDA Guidance is released, she added, there are plans to update the AMCP Format in response.