FDA Issues Draft Guidance on Responding to Unsolicited Requests for Off-Label Information and Opens Docket on Off-Label and Pre-Approval Communications

By Jamie K. Wolszon & Alan M. Kirschenbaum –

FDA has issued two important documents bearing on communications regarding off-label uses and (in one of the documents) not-yet-approved products.  The first, which was posted on FDA’s web site earlier this week, was a draft guidance on how a drug, biologics, or device manufacturer should respond to unsolicited requests for off-label information.  The draft guidance addresses both private requests and requests made in public forums, including emerging electronic media such as product websites, discussion boards, or web chat-rooms.  Although FDA’s policy permitting companies to respond to unsolicited requests dates back at least to 1982, this guidance is the most detailed exposition of the policy to date, and, of course, the only one that addresses emerging electronic media.  FDA explains that, if a manufacturer responds to an unsolicited request in the manner set forth in the guidance, FDA will not use the response as evidence of the firm’s intent that the product be used for an unapproved or uncleared use, and the response also will not be regulated as promotional labeling or advertising.

The draft guidance applies to all approved or cleared prescription human and animal drugs (including biologics) and medical devices for humans.  FDA explains that cleared or approved devices include, not only those subject to 510(k) notification or PMA approval, but also “devices that are legally marketed for a specific intended use without an individual product approval or substantial equivalence determination”, e.g. class I and II devices marketed for a use exempt from the PMA or 510(k) processes.  For those devices, the draft guidance defines a request for off-label information as “any request for information regarding a new use for which approval or clearance would be required.”  The draft guidance does not cover medical products that are not currently approved or cleared for any purpose.

The draft guidance defines an unsolicited request as one that is not prompted in any way by a manufacturer or its representatives and that is initiated by persons or entities that are completely independent of the relevant firm, including health care professionals, health care organizations, members of the academic community, formulary committees, patients, and caregivers.  By contrast, a solicited request is one that is “prompted in any way by a manufacturer or its representatives . . .”  A number of examples of solicited requests are provided.

The draft guidance distinguishes between public and non-public unsolicited requests.  A non-public unsolicited request is one made “directly to a firm using a one-on-one communication approach” such as an individual who calls or emails the medical information staff at a firm.  A public unsolicited request is one “made in a public forum, whether directed to a firm specifically or to a forum at large,” such as a question posed to a firm representative during a live presentation and heard by other attendees, or a question about an off-label use of a specific product posted on a firm-controlled website or a third-party discussion forum visible to a broad audience. 

The guidance on non-public unsolicited requests is generally consistent with FDA’s historical policy on such requests:  responses should be provided only to the requestor as a one-on-one communication.  They should be scientific and non-promotional in tone and presentation; generated by medical or scientific personnel independent from sales or marketing; tailored to answer only the specific question asked; and truthful, non-misleading, accurate, and balanced.  The response should be accompanied by a copy of the FDA-approved labeling, a statement that FDA has not approved or cleared the product for the use(s) described in the response, a statement of the approved or cleared indication, all important safety information, and a list of references.  Records should be kept of the request, the response, and any follow-up inquiries.

The section of the draft guidance on public unsolicited requests ventures into new areas that have not heretofore been addressed in FDA policy statements.  FDA explains that it has two concerns with providing off-label information in a public forum in response to an unsolicited public request.  First, by answering the question in public, the manufacturer exposes those who did not make the request to the off-label information.  Moreover, due to the enduring nature of websites, the information may remain available in the public domain even after it becomes outdated.  Accordingly, the draft guidance provides that a company’s public response to a public request cannot provide any of the requested off-label information.  Instead, the company representative must note that the information requested is off-label and then provide the contact information of the company’s medical/scientific personnel.  Also, a company should only respond to a request that specifically references the company’s own named product.  Note that these restrictions apply, not only to requests made on electronic forums, but also those made by attendees at a live meeting. 

If the individual making the request follows up with the company, the guidelines for responding are the same as those for responding to a non-public unsolicited request, described above. 

In a separate but related development, the December 28th Federal Register contained an FDA notice announcing the opening of a docket to receive comments on scientific exchange involving off-label uses of approved/cleared products or products for which there is not yet any approval or clearance.  FDA opened this docket in response to a Citizen Petition filed by several pharmaceutical companies requesting that FDA clarify its policies regarding communications related to off-label uses and pre-approval communications (see our previous post here).  The notice specifically requests comments on “scientific exchange.”  Under FDA’s drug and device regulations and Agency policy, the “exchange of scientific information” concerning an investigational drug or device is not subject to restrictions on promotion, but FDA has not yet attempted to define the scope of “scientific exchange.”  The Agency is seeking comments and information on scientific exchange to assist it in evaluating FDA policies on off-label and pre-approval communications.  FDA asks for responses to a number of specific questions, including how scientific exchange should be defined, what kinds of activities are included, how it should be distinguished from promotion, and whether off-label communications should be treated differently from pre-approval communications.  Comments may be submitted through March 27, 2012.