FDA’s New Off-Label Guidance: What it Says and What it Leaves Unanswered

May/June 2012Articles FDLI Update

On December 30, 2011, the Food & Drug Administration (FDA) released a draft guidance document entitled Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices (Guidance)[1]. The Guidance purports to respond to stakeholder requests for clarification of FDA’s policy regarding distribution of prescription drugs and, to some degree, accomplishes this goal. The Guidance also purports to deal with promotional issues concerning the use of the Internet and other emerging electronic media. However, the Guidance falls short of its mark on a topic the regulated community has been seeking answers for several years.

The Guidance

Under the Food, Drug, and Cosmetic Act (FDCA), promoting a drug for a use other than that approved by FDA is generally illegal. Health care professionals (HCPs) can lawfully prescribe a drug for an unapproved use. FDA recognizes the benefits of such off-label uses as well as the fact that manufacturers may be in possession of information that would assist HCPs in gaining quick access to useful information about a drug’s therapeutic value. the Guidance
operates upon this legal backdrop.

The Guidance traces its genesis in part to FDA’s solicitation in 2009 of comments on the use of the Internet and social media[2], and the subsequent public hearings that it conducted on that same subject in November 2009. FDA was particularly interested in providing tools for manufacturers to respond to inquiries generated in the electronic media context, yet also avoiding accusations that off-label uses were being promoted in the manufacturers’ responses. On the other hand, FDA did not want to chill the meaningful exchange of scientific information via electronic media.

The Guidance was crafted to address a portion of a July 2011 citizen petition that had been filed on behalf of seven manufacturers. That petition sought FDA clarification on a number of topics, including manufacturers’ interest in legally responding to unsolicited requests concerning off-label uses of approved products[3].

To put it simply, the Guidance is intended to provide a framework for manufacturers to legally respond to unsolicited off-label requests for information, and nothing more.

Solicited and Unsolicited Requests

Solicited Requests are those that are prompted in any way by a manufacturer or its sales representatives, whether in person or via websites or other electronic media. These responses are not addressed in the Guidance – except that FDA provides numerous examples of solicited requests, including those that may give rise to statutory violations. Accordingly, solicited requests will not be protected in the same manner as the generally protected scheme that the Guidance establishes for unsolicited requests.

Unsolicited Requests are those that are initiated independent of a manufacturer. These are typically from HCPs and patients, among others, and request information about an off-label use. These unsolicited requests represent most of the off-label information requests received by manufacturers and can be either public or non-public in nature.

Non-public unsolicited requests for information are those specifically directed to a manufacturer via one-to-one communication. Public unsolicited requests, on the other hand, are those made in a public forum such as during a speaker presentation or via a website forum or chat room. Because public unsolicited requests occur in the least controlled environment, they carry the greatest risk for manufacturers.

If the Guidance were adopted in its current form, then public and non-public requests should be addressed differently.

How to Address Non-Public Unsolicited Requests

Non-public unsolicited requests should be addressed as follows:(1) the response should be addressed only to the individual making the request; (2) the response should address only the specific questions asked; (3) the response should be truthful, non-misleading, accurate and balanced (i.e., risk information should be presented if available), and published peer-reviewed journals, medical texts or data derived from independent sources should be used instead of manufacturer-sponsored data; (4) responses should be scientific in nature; (5) responses should be generated by the manufacturer’s medical or scientific personnel and not by sales or marketing departments; and (6) responses should be accompanied by the following:
• A copy of FDA-approved labeling;
• A prominent statement that FDA has not approved the drug for the off-label use;
• A prominent statement disclosing the indication for which FDA has approved the drug;
• A prominent statement providing all pertinent safety information including boxed warnings; and
• A complete list of references for all of the information disseminated in the response.

Manufacturers should also maintain records of: (1) the nature of the request for information; (2) the information provided to the requestor; and (3) any follow-up inquiries and responses.

How to Address Public Unsolicited Requests

Public unsolicited requests should be addressed as follows: (1) The manufacturer should respond only when the request pertains specifically to its products; (2) any public response should be limited to providing firm contact information (e.g., the names and contact information of medical or scientific representatives) and should not include any off-label information; (3) any public response should disclose the affiliation with the manufacturer of the person making the response; and (4) responses should never be promotional in nature.

What this Means for Manufacturers

Under the Guidance, unsolicited requests that are addressed in the manner discussed above, whether public or non-public, will not be used by FDA as evidence that a manufacturer is promoting its products for off-label uses.

Manufacturers should expect that unsolicited requests for off-label information would continue to be submitted. They must exercise caution in responding and be certain to include the required information with each and every response. Records of all requests and responses must also be maintained.

Manufacturers should also continue to prohibit discussion groups on their own websites and on any product websites. These are difficult to control and, more importantly, difficult to maintain within the strict boundaries of the Guidance.

Finally, speakers should only respond to off-label inquiries by providing medical or scientific liaison officer contact information. Off-label information should not be provided in the presentation context, and speakers should be specifically prohibited from providing a response that includes the speakers’ experience with a drug. Stated differently, speakers might be able to provide responses relating to their experience with particular classes of drugs but cannot provide information on experiences with specific drugs.

Unanswered Questions and the Opportunity to Comment

The comment period for addressing the Guidance’s substantive impact on the promotion of off-label uses, and responding to both solicited and unsolicited requests for information, expired on March 29, 2012. Therefore, manufacturers should consider the following.

Although the Guidance purports to address the topics originally raised in 2009, it leaves a litany of subjects open for varying interpretations of what is legal and what is not. For example, the Guidance does not address the extent to which a manufacturer can promote its products via blogs or social media sites such as microblogs (e.g., Twitter) and social networks (e.g., Facebook). By way of further example, in 2009 FDA began its public dialogue on:

• The types of online communications for which manufacturers could be held accountable;
• The methods by which manufacturers could fulfill regulatory requirements in their Internet and social media promotion;
• The parameters by which manufacturers and other could correct misconceptions found on third party Internet sites;
• The appropriateness of using web links; and
• Using the Internet for adverse event reporting [4]

The lack of clarity on most of these topics will remain even if the Guidance is adopted.

Finally, the Guidance, if adopted, will not establish legally enforceable rights or responsibilities but, instead, only represent FDA’s “current thinking” on the topic. The regulated community should, therefore, treat the Guidance as a first step in what promises to be a many-layered process of defining acceptable conduct.

Reprinted with the Permission of FDLI.

[1] 76 Fed. Reg. 82303 (Dec. 30, 2011), Guidance available at http://www.fda.gov/downloads/Drugs/Guidance-ComplianceRegulatoryInformation/Guidances/UCM285145.pdf (PDF) (last visited March 5, 2012).

[2] See, e.g., 74 Fed. Reg. 48083 (Sept. 21, 2009).

[3] Petition available at http://op.bna.com/hl.nsf/r?Open=deln-8jkr2b (PDF).

[4] 74 Fed. Reg. 48083 (Sept. 21, 2009).