Introduction

On Tuesday December 27, 2011, the U.S. Food and Drug Administration (FDA) issued draft guidance to drug and device companies on responding to unsolicited requests for off-label information related to their FDA-approved or cleared products. The draft guidance covers both: 1) responding to requests made directly and privately to companies, and 2) requests made in public forums, including through emerging electronic media.

Background

By law, drug and device companies (manufacturers and distributers) are prohibited from marketing and promoting their products for uses beyond those approved or cleared by the FDA. However, once a drug or medical device has been approved or cleared by the FDA, physicians can (in most cases) lawfully use or prescribe that product for indications that are not included in the product's approved labeling on a case by case basis (or, in the case of a medical device cleared under the 510(k) process, in the product's statement of intended uses). Because "off-label" uses may provide important treatment options for patients and may even constitute a medically recognized standard of care, physicians, patients and/or their advocates often seek information about such off-label use –sometimes requesting off-label information directly and privately to firms.

According to the FDA, a growing number of consumers (patients and providers) are turning to the Internet as a source for information about treating medical conditions. Moreover, drug and device companies, are increasingly using the Internet to disseminate information about their products. Consequently, companies may receive requests for off-label information about their products through product websites that they maintain and over which they have full control. However, the FDA acknowledges that there exist a number of third-party websites, including online discussion boards, chat rooms, and other public, web-based forums that are either entirely independent of a company's control and influence or not fully controlled by a company, and in which may also reveal questions about off-label uses of that organization's products. Often, such questions about off-label uses are directed to users of the website generally, rather than directly and privately to companies who, according to the FDA, "are capable of responding to requests about their own named products in a truthful, non-misleading, and accurate manner." Furthermore, the FDA deems it to be in the best interest of public health for a company to respond to unsolicited requests for information about off-label uses of its products that are addressed to a public forum, since 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 company's products.

FDA Policy on Responding to Unsolicited Requests for Off-Label Information

For decades, the FDA has said that companies can respond to unsolicited requests for off-label information with "truthful, balanced, non-misleading, and non-promotional scientific or medical information that is responsive to the specific request," without subjecting their products to the strict regulatory requirements for promotional labeling or advertizing. This draft guidance does not deviate from the FDA's long held position. Merely, it explains in detail the FDA's recommendations for responding to each type of request for off-label information –"non-public" and public.

Non-Public Responses

For a company's response to a non-public unsolicited request for off-label information about its product that was specifically directed to the company privately through a one-on-one communication, the Agency has provided the following 7 recommendations:

1. Information distributed in response to an unsolicited request should be provided only to the individual making the request [and handled] as a private, one-on-one communication.

2. Information distributed in response to an unsolicited request should be tailored to answer only the specific question(s) asked.

In other words, if the company receives a broad question, it should appropriately narrow the question to ensure that its response is tailored to the request. However, in tailoring its answers to the specific question, companies are reminded to completely and accurately present the risks associated with the requested off-label use, even when the known or suspected risks are associated with diseases or conditions other than the disease or condition for which the information was requested. For example, the FDA explains, if "Drug X is known to cause fetal harm when used in pregnant patients with arthritis [...] this risk information should be disclosed as part of the response about use of Drug X during pregnancy in patients with diabetes."

3. Information distributed in response to an unsolicited request should be truthful, non-misleading, accurate, and balanced

Furthermore, the information should be unabridged and not just summary documents or abstracts prepared by the company. The FDA encourages companies to "rely on published peer-reviewed journal articles, medical texts, or data derived from independent sources."

4. Information distributed in response to an unsolicited request should be scientific in nature

This information should not be promotional in tone or presentation, nor should it be distributed along with other material or information that is promotional in nature or tone.

5. Responses to unsolicited requests for information should be generated by medical or scientific personnel independent from sales or marketing departments.

Because sales and marketing personnel are focused on promoting a company's products, the FDA recommends that these personnel have no input whatsoever on the content of responses to unsolicited questions or requests for off-label information.

6. Information distributed in response to an unsolicited request should be accompanied by the following:

  • A copy of the FDA-required labeling, if any, for the product (e.g., FDA-approved package insert and, if the response is for a consumer, FDA-approved patient labeling or, for new animal drugs, FDA-approved client information sheet)
  • A prominent statement notifying the recipient that FDA has not approved or cleared the product as safe and effective for the use addressed in the materials provided
  • A prominent statement disclosing the indication(s) for which FDA has approved or cleared the product
  • A prominent statement providing all important safety information including, if applicable, any boxed warning for the product
  • A complete list of references for all of the information disseminated in the response (e.g., a bibliography of publications in peer-reviewed medical journals or in medical or scientific texts; citations for data on file, for summary documents, or for abstracts)

7. A [company] should maintain the following records:

  • The nature of the request for information, including the name, address, and affiliation of the requestor
  • Records regarding the information provided to the requestor
  • Any follow-up inquiries or questions from the requestor

Public Responses

As noted above, the FDA insists that companies "are capable of responding to requests about their own named products in a truthful, non-misleading, and accurate manner." Nevertheless, the Agency is concerned about the possibility that companies may respond to public unsolicited questions about off-label uses of their products in a manner that promotes off-label use to individuals who have not requested such information, because product information posted to websites and other electronic forums is likely to remain "available to a broad audience for an indefinite period of time." Citing the availability of new data on product risks becoming available in the future, the FDA expressed additional concern that publically posted responses may become outdated.

Therefore, in support of a company's response to a public unsolicited request for off-label information about its product, including questions encountered through websites and other emerging electronic media, the FDA has provided the following 4 recommendations:

1. If a [company] chooses to respond to public unsolicited requests for off-label information, the [company] should respond only when the request pertains specifically to its own named product (and is not solely about a competitor's product).

For example, a company should not respond to non-specific questions or requests, such as "What drug/device can be used for Condition X?".

2. A [company's] public response to public unsolicited requests for off-label information about its named product should be limited to providing the firm's contact information and should not include any off-label information.

  • The [company's] public response should convey that the question pertains to an unapproved or uncleared use of the product and state that individuals can contact the medical/scientific representative or medical affairs department with the specific unsolicited request to obtain more information.
  • The [company's] public response should provide specific contact information for the medical or scientific personnel or department (e.g., e-mail address, telephone number, facsimile [number]) so that individuals can follow up independently with the firm to obtain specific information about the off-label use of the product through a non-public, one-on-one communication.

After the individual makes his or her request to the company privately through a one-on-one communication, the company should adhere to the 7 recommendations for responding to non-public unsolicited requests for off-label information, as noted above. The FDA's intent behind this recommendation is to ensure that the exchange of off-label information will take place solely between the company and the specific individual making the unsolicited request.

3. Representatives who provide public responses to unsolicited requests for off-label information should clearly disclose their involvement with a particular [company].

4. Public responses to public unsolicited requests for off-label information described in numbers 2 and 3 should not be promotional in nature or tone.

The FDA also suggests that in addition to responding with contact and disclosure information, company representatives' responses should include a mechanism for providing readily accessible and current FDA-approved or -cleared labeling for the product, such as a hyperlink or website address where the individual can find such labeling. However, the Agency specifically calls attention to the types of product websites, company websites and third-party websites where individuals should not be directed, including websites whose uniform resource locator (URL) or web address is itself "promotional in tone or content (e.g., [...] www.bestcancercure.com)."

Summary

Regardless of where the unsolicited request for off-label information was made—in a non-public or public forum—the FDA recommends that a company only provide the requested off-label information about its product to the specific individual who requested the information in a private, one-on-one communication.

The FDA does not intend to use the responses of companies to unsolicited requests for off-label information as evidence that a company is purposefully promoting its product(s) off-label, if such responses conform to the recommendations provided within the draft guidance. Additionally, responses that conform to this guidance would not be expected to comply with the disclosure requirements related to promotional labeling and advertizing.

The complete FDA draft guidance can be found here. Those planning to submit comments or suggestions regarding the draft document will have 90 days from the date of its publication in the Federal Register.

Should you have any questions regarding this FDA Draft Guidance, please contact any of the SNR Denton Health and Life Sciences professionals. We are pleased to assist you in any way.

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