The Food and Drug Administration (“FDA” or “Agency”) recently published a notice in the Federal Register seeking comments on the scientific exchange of information about investigational new drugs and investigational medical devices (the “Notice”). The Notice, which appeared in the Federal Register on December 28, 2011, explained that the Agency is requesting information that will help it evaluate its policies on the communication of off-label information about drugs and devices already marketed, as well as the promotion of drugs and devices not yet approved for marketing by the FDA. Comments may be submitted through March 27, 2012.

The FDA also issued a draft guidance entitled, Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices (the “Draft Guidance”). The FDA explained that the Draft Guidance, which was published in the Federal Register on December 30, 2011, “updates and clarifies FDA’s policies on unsolicited requests for off-label information, including those that firms may encounter through emerging electronic media.” The notice further referenced a public hearing held on November 12-13, 2009, on the “Promotion of FDA-Regulated Medical Products Using the Internet and Social Media Tools,” and stated that the Draft Guidance “is the first of multiple draft guidances the Agency plans to publish that addresses questions and issues related to emerging electronic media.” Interested parties are invited to submit comments on the Draft Guidance by March 29, 2012. 

Background

The Federal Food, Drug, and Cosmetic Act (“FD&C Act” or the “Act”) and FDA’s implementing regulations prohibit the introduction into interstate commerce of new drugs and most Class III medical devices for any intended use that the FDA has not determined to be safe and effective. The FD&C Act and the Agency’s implementing regulations also prohibit the introduction into interstate commerce of medical devices subject to premarket notification requirements under section 510(k) of the Act (which includes most Class II and some Class I devices) for any intended use that is outside of FDA’s substantial equivalence determination (i.e. “clearance”) for such devices. 

FDA has long taken the position that the promotion of a drug or medical device for uses other than those approved or cleared by the Agency (i.e. “off-label promotion”) may be used as evidence of a new intended use. The introduction of a drug or medical device for a new intended use without FDA approval or clearance generally constitutes a violation of the FD&C Act and FDA regulations. 

Healthcare professionals, however, may nevertheless prescribe or use approved or cleared drugs or devices for indications that are not included in the product’s approved labeling (or in the product’s statement of intended uses in the case of a medical device cleared under the 510(k) process). The Draft Guidance recognizes that such “off-label uses or treatment regimens may be important options and may even constitute a medically recognized standard of care.” 

In addition to its prohibition on off-label promotion, FDA prohibits the promotion of drugs and medical devices that have not yet been approved or cleared for any use (i.e. “pre-approval promotion”). The FDA, however, has stated that its prohibition on pre-approval promotion of investigational drugs and devices is not intended to stifle scientific exchange. For example, FDA’s regulations on investigational new drugs state that the prohibition on pre-approval promotion “is not intended to restrict the full exchange of scientific information concerning the drug, including dissemination of scientific findings in scientific or lay media.” To date, the Agency has not attempted to define the scope of “the full exchange of scientific information.”

Request for Comments on Scientific Information

The FDA acknowledged that the Notice on scientific exchange was prompted by a citizen petition that was submitted last July on behalf of seven manufacturers who requested clarification on certain Agency policies relating to off-label and pre-approval promotion. Specifically, the citizen petition requested that the FDA clarify its policies on responding to unsolicited requests, scientific exchange, interactions with formulary committees and payors, and dissemination of third-party clinical practice guidelines. 

The Notice states that the Agency is requesting “detailed comment on all aspects of scientific exchange communications and activities related to off-label uses of marketed drugs, biologics, and devices and use of products that are not yet legally marketed.” In addition, the Agency is particularly interested in responses to the following questions:

• How should FDA define scientific exchange?
• What types of activities fall under scientific exchange?
• What types of activities do not fall under scientific exchange?
• Are there particular types and quality of data that may indicate that an activity is, or is not, scientific exchange?
• In what types of forums does scientific exchange typically occur?
• What are the distinctions between scientific exchange and promotion?
• Who are the speakers involved in scientific exchange, and who is the audience for their communications?
• Should the identity of the participants be given particular significance in determining whether an activity is scientific exchange or product promotion?
• How do companies generally separate scientific roles and promotional roles within their corporate structures?
• How should FDA treat scientific exchange concerning new uses under FDA-regulated investigation versus uses that are not under such regulation?
• How should the Agency treat scientific exchange concerning use of products that are not yet legally marketed?
• Should investigational drugs and investigational devices be treated the same with respect to scientific exchange?
• What actions, other than those specified in the regulations, indicate the commercialization of drugs and/or devices?

The Notice explains that it is seeking responses to these questions to assist with its evaluation of its policies on communications and activities related to off-label and pre-approval promotion. 

Two Types of Unsolicited Requests

In the related Draft Guidance on unsolicited requests for off-label information, the FDA describes “unsolicited requests” as “those 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, and formulary committees, as well as consumers such as patients and caregivers.” Conversely, a request is considered “solicited” if it is “prompted in any way by a manufacturer or its representatives.” FDA may consider such solicited requests for off-label information as evidence of a company’s intent that a product be used for an indication that has not been approved or cleared by the Agency. 

Although the Draft Guidance is generally consistent with its prior policy pronouncements on unsolicited requests for off-label information, which date back at least to 1982, the draft distinguishes between two types of unsolicited requests: non-public and public. A “non-public unsolicited request” is described in the Draft Guidance as “an unsolicited request that is directed privately to a firm using a one-on-one communication approach.” FDA offers as an example of a non-public unsolicited request a scenario in which an individual calls or e-mails a firm’s medical affairs staff seeking off-label information. In such a scenario, neither the individual’s request nor the company’s response would be visible to the public. 

A “public unsolicited request” is described in the Draft Guidance as “an unsolicited request made in a public forum, whether directed to a firm specifically or to a forum at large.” Examples of public unsolicited requests include scenarios in which an individual asks a question regarding an off-label use during a live presentation or posts a question about an off-label use on either a firm-controlled website or a third-party discussion forum that is visible to a broader audience. The Draft Guidance “recognizes that it can be in the best interest of public health for a firm to respond to” such public unsolicited requests, given that “other participants in the forum who offer responses may not provide or have access to the most accurate and up-to-date information about the firm’s products.” FDA, however, is concerned that off-label information provided by firms on a public electronic forum may be communicated to individuals who have not requested such information and may endure even after becoming outdated. 

FDA’s Recommendations for Responding to Unsolicited Requests 

The Draft Guidance provides the following recommendations with respect to a firm’s responses to non-public unsolicited requests for off-label information:

1. Responses should be provided only to the individual making the request directly to the firm as a private, one-on-one communication.
2. The response should be tailored to answer only the specific question(s) asked.
3. Responses should be truthful, non-misleading, accurate, and balanced.
4. The response should be scientific in nature.
5. Responses should be generated by medical or scientific personnel: “FDA recommends that sales and marketing personnel have no input on the content of [such] responses.”
6. Responses should be accompanied by the following:

• A copy of the FDA-approved labeling,
• A prominent statement that the FDA has not approved or cleared the product as safe and effective for the use at issue,
• A prominent statement disclosing the indication(s) for which the FDA has approved or cleared the product,
• A prominent statement providing all important product safety information including, if applicable, any boxed warning, and
• A complete list of references.

In addition, the Draft Guidance recommends that firms maintain the following records associated with their responses to non-public requests:

1. The nature of the information request, including the requestor’s name, address, and affiliation, 
2. The information provided to the requestor, and
3. Any follow-up questions from the requestor. 

Of note, the Draft Guidance is the first time that the FDA has given guidance on how companies may use the internet and social media tools. According to the Draft Guidance, responses to public unsolicited requests, “including those encountered through emerging electronic media” (e.g., Twitter, Facebook, etc.), should not be made to the entire audience in the electronic forum, but instead should be made privately, to the person requesting the information. Specifically, the

Draft Guidance makes the following recommendations with respect to public unsolicited requests:

1. The firm should respond only to requests that pertain specifically to its own product.
2. The firm’s public response should be limited to its contact information and should not include any off-label information.
3. Representatives who provide responses should clearly disclose their affiliation.
4. Responses should not be promotional in nature or tone.

FDA recommends that after an individual has privately contacted a firm for off-label information, the firm’s response and recordkeeping should comply with the parameters enumerated above in connection with responses to non-public unsolicited requests. 

The Draft Guidance observes that, to the extent a firm follows the recommendations for responding to both types of unsolicited requests set forth above, “FDA does not intend to use such responses as evidence of the firm’s intent that its product be used for an unapproved or uncleared use.” In addition, such responses would not be required to comply with the disclosure requirements applicable to promotional labeling and advertising. 
 

D. Kyle Sampson is a partner in the Washington, D.C. office of Hunton & Williams LLP (www.hunton.com) and a member of the Firm’s Food and Drug Practice. He can be reached by email at ksampson@hunton.com. Brian J. Wesoloski is an associate in the Firm’s Food and Drug Practice. He can be reached at bwesoloski@hunton.com.