Notice: Draft Guidance for Industry on Responding to Unsolicited Requests 
for Off-Label Information About Prescription Drugs and Medical Devices; 
Availability

Federal Register: Volume 76, Number 251 (Friday, December 30, 2011)
                  Pages 82303-82306

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry entitled ``Responding to 
Unsolicited Requests for Off-Label Information About Prescription Drugs 
and Medical Devices.'' This draft guidance responds to stakeholder 
requests for specific guidance on FDA's current views on how 
manufacturers and distributors (firms) of prescription human and animal 
drug products and

[[Page 82304]]

medical devices can respond to unsolicited requests for information 
about unapproved or uncleared indications or conditions of use (off-
label information) related to their FDA-approved or cleared products. 
This draft guidance updates and clarifies FDA's policies on unsolicited 
requests for off-label information, including those that firms may 
encounter through emerging electronic media.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the Agency considers your comments on 
this draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by March 29, 2012. Submit written comments on the proposed 
collection of information by February 28, 2012.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Office of Communications, Division of Drug Information, 
Center for Drug Evaluation and Research, Food and Drug Administration, 
10903 New Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-
0002; to the Office of Communication, Outreach and Development (HFM-
40), Center for Biologics Evaluation and Research, Food and Drug 
Administration, 1401 Rockville Pike, suite 200N, Rockville, MD 20852-
1448; to the Communications Staff, Center for Veterinary Medicine, Food 
and Drug Administration, 7519 Standish Pl. (HFV-12), Rockville, MD 
20855; or to the Division of Small Manufacturers, International and 
Consumer Assistance, Office of Communication, Education and Radiation 
Programs, Center for Devices and Radiological Health, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 66, rm. 4613, Silver 
Spring, MD 20993-0002. Send one self-addressed adhesive label to assist 
that office in processing your requests. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the draft guidance 
document.
    Submit electronic comments on the draft guidance to http://www.regulations.gov. 
Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: 
    Regarding human prescription drugs: Jean-Ah Kang, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Silver Spring, MD 20993, (301) 796-1200.
    Regarding prescription human biological products: Stephen Ripley, 
Center for Biologics Evaluation and Research (HFM-17), Food and Drug 
Administration, 1401 Rockville Pike, suite 200N, Rockville, MD 20852-
1448, (301) 827-6210.
    Regarding animal prescription drugs: Dorothy McAdams, Center for 
Veterinary Medicine (HFV-216), Food and Drug Administration, 7519 
Standish Pl., Rockville, MD 20855, (240) 276-9300.
    Regarding medical devices: Deborah Wolf, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Silver Spring, MD 20993, (301) 796-5732.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Responding to Unsolicited Requests for Off-Label Information 
About Prescription Drugs and Medical Devices.'' In July 2011, FDA 
received a citizen petition, filed on behalf of seven prescription drug 
manufacturers, seeking additional clarification on several areas of FDA 
policy regarding distribution of information about prescription drugs. 
One of the areas was how to respond to unsolicited requests from health 
care professionals or consumers for information about off-label uses of 
approved products.
    In addition, on November 12 and 13, 2009, FDA held a Part 15 public 
hearing on ``Promotion of FDA-Regulated Medical Products Using the 
Internet and Social Media Tools'' to provide an opportunity for broad 
public participation and comment on the following questions that relate 
specifically to promotional issues: (1) For what online communications 
are manufacturers, packers, or distributors accountable? (2) How can 
manufacturers, packers, or distributors fulfill regulatory requirements 
(e.g., fair balance, disclosure of indication and risk information, 
post-marketing submission requirements) in their internet and social 
media promotion, particularly when using tools that are associated with 
space limitations and tools that allow for real-time communications 
(e.g., microblogs, mobile technology)? (3) What parameters should apply 
to the posting of corrective information on Web sites controlled by 
third parties? (4) When is the use of links appropriate? Subsequent to 
the live testimony heard at the Part 15 public hearing, FDA received 72 
comments to the docket. This draft guidance is the first of multiple 
draft guidances the Agency plans to publish that address questions and 
issues related to emerging electronic media.
    This draft guidance provides FDA's recommendations to firms wishing 
to respond to unsolicited requests for off-label information about 
their products, including both requests made directly and privately to 
firms and requests made in public forums, including through emerging 
electronic media. This draft guidance discusses the difference between 
unsolicited and solicited requests and presents a number of examples of 
both types of requests. If a firm responds to unsolicited requests for 
off-label information in the manner described in this draft guidance, 
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. 
Such responses also would not be expected to comply with the disclosure 
requirements related to promotional labeling and advertising. Firms may 
choose to respond to unsolicited requests for information about off-
label uses of their approved or cleared products in a manner other than 
that recommended in this draft guidance. Such activity would not 
constitute a per se violation of the law, but could potentially be 
introduced as evidence of a new intended use.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the Agency's current thinking on responding 
to unsolicited requests for off-label information about prescription 
drugs and medical devices. It does not create or confer any rights for 
or on any person and does not operate to bind FDA or the public. An 
alternative approach may be used if such approach satisfies the 
requirements of the applicable statutes and regulations.

II. The Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 
3501-3520), Federal agencies must obtain approval from the Office of 
Management and Budget (OMB) for each collection of information they 
conduct or sponsor. ``Collection of information'' is defined in 44 
U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or 
requirements that members of the public submit reports, keep records, 
or provide information to a third party. Section 3506(c)(2)(A) of the 
PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a 
60-day notice in the Federal Register concerning each proposed 
collection of information

[[Page 82305]]

before submitting the collection to OMB for approval. To comply with 
this requirement, FDA is publishing notice of the proposed collection 
of information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on these topics: (1) Whether the proposed collection 
of information is necessary for the proper performance of FDA's 
functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information collected; and (4) ways to 
minimize the burden of information collected on the respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.
    Title: Industry Responses to Unsolicited Requests for Off-Label 
Information About Prescription Drugs and Medical Devices.
    Description of Respondents: Respondents to this collection of 
information are manufacturers and distributors (firms) of prescription 
human and animal drug products or medical devices.
    Burden Estimate: The draft guidance pertains to the dissemination 
of scientific or medical information about off-label uses for approved 
or cleared products by FDA-regulated industry when it responds to (1) 
non-public unsolicited requests for off-label information made directly 
and privately to them, or (2) public unsolicited requests for off-label 
information, including those that firms may encounter through emerging 
electronic media.
    The draft guidance explains that FDA's current policy position is 
that, regardless of whether the initial unsolicited request for off-
label information was made in a non-public or public forum, FDA does 
not intend to use the firm's actions as evidence of a new intended use, 
nor expect distributed materials to conform to existing regulatory 
requirements for promotional labeling or advertising, if the firm 
responds in the manner outlined in the guidance. Specifically, the 
draft guidance recommends that a firm that chooses to respond to an 
unsolicited request for off-label information 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, one-on-one communication. FDA also recommends that 
information distributed in response to an unsolicited request be 
truthful, non-misleading, accurate, balanced, and non-promotional 
scientific or medical information that is tailored to answer only the 
specific question asked, even if responding to the request requires the 
firm to provide information regarding unapproved or uncleared 
indications or conditions of use. To meet this standard, the draft 
guidance recommends that firms disclose certain information to others 
when responding to their unsolicited requests. This ``third-party 
disclosure'' constitutes a ``collection of information'' under the PRA. 
In addition, the PRA is triggered because the draft guidance also 
recommends that firms maintain certain records related to this 
disclosure.

Non-Public Responses

    When providing non-public responses to unsolicited requests for 
information about unapproved or uncleared indications or conditions of 
use, the draft guidance recommends the following:
     A response should provide non-biased information or data 
relating to the particular off-label use that is the subject of the 
request, including applicable data that are not supportive or that cast 
doubt on the safety or efficacy of that use. For example, when 
conclusions of articles or texts that are disseminated have been 
specifically called into question by other articles or texts, a firm 
should disseminate representative publications that reach contrary or 
different conclusions regarding the use at issue. The response should 
include complete copies of scientific reprints, technical literature, 
or other scientific and medical information responsive to the request, 
not just summary documents or abstracts prepared by the firm. The 
response may include unpublished data on file if they are responsive to 
the specific request (either supporting or casting doubt on the safety 
or efficacy of the off-label use). However, to the greatest extent 
possible, a firm should rely on published peer-reviewed journal 
articles, medical texts, or data derived from independent sources. To 
the extent the response consists of published reprints from journals, 
those reprints should be from journals that have a publicly stated 
policy, to which the organization adheres, of full disclosure of any 
conflict of interest or biases for all authors, contributors, or 
editors associated with the journal or organization.

In addition to responsive materials as described previously in this 
document, the guidance recommends that the following information be 
provided to the requestor:
    1. 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).
    2. 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.
    3. A prominent statement disclosing the indication(s) for which FDA 
has approved or cleared the product.
    4. A prominent statement providing all relevant safety information 
including, if applicable, any boxed warning for the product.
    5. 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).
    Finally, the draft guidance recommends that a firm maintain the 
following related records:
    1. The nature of the request for information, including the name, 
address, and affiliation of the requestor.
    2. Records regarding the information provided to the requestor.
    3. Any followup inquiries or questions from the requestor.

Public Responses

    When providing public responses to unsolicited requests for 
information about unapproved or uncleared indications or conditions of 
use, the draft guidance recommends that the following information be 
disclosed to the requestor:
    1. A firm's public response to public unsolicited requests for off-
label information about its named product should convey that the 
question pertains to an unapproved or uncleared use of the product and 
be limited to providing the firm's contact information for the medical 
or scientific personnel or department 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 an individual has privately contacted the firm for 
more information regarding an off-label use of the firm's product, the 
firm should provide a detailed response and maintain records following 
the parameters outlined in Section V of the draft guidance (and 
summarized previously in this

[[Page 82306]]

document for non-public responses to unsolicited requests).
    2. Representatives who provide public responses to unsolicited 
requests for off-label information should clearly disclose their 
involvement with a particular firm.
    3. Public responses to public unsolicited requests for off-label 
information should not be promotional in nature or tone and should 
include a mechanism for providing readily accessible 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).
    FDA estimates that approximately 400 firms respond annually to 
approximately 40,000 non-public unsolicited requests for off-label 
information made directly and privately to them as well as to public 
unsolicited requests for off-label information, including those that 
firms may encounter on emerging electronic media. FDA estimates that it 
will take firms approximately 4 hours to provide responses to each 
unsolicited request for off-label information as recommended in the 
draft guidance.
    FDA also estimates that approximately 40,000 records will be 
maintained for all responses to non-public and public unsolicited 
requests for off-label information, and that each record will take 
approximately 15 minutes to prepare and maintain.

                                                      Table 1--Estimated Annual Reporting Burden 1
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                         Number of
 Draft guidance on responding to unsolicited requests for off-label     Number of      responses per     Total annual    Average burden    Total hours
                            information                                respondents       respondent       responses       per response
--------------------------------------------------------------------------------------------------------------------------------------------------------
Responses to non-public and public unsolicited requests............              400              100           40,000                4          160,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


                                                    Table 2--Estimated Annual Recordkeeping Burden 1
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                         Number of                      Average  burden
 Draft guidance on responding to unsolicited requests for off-label     Number of       records per      Total annual         per          Total hours
                            information                               recordkeepers     recordkeeper       records       recordkeeping
--------------------------------------------------------------------------------------------------------------------------------------------------------
Records related to responses to non-public and public unsolicited                400              100           40,000              .25           10,000
 requests..........................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

III. Comments

    Interested persons can submit to the Division of Dockets Management 
(see ADDRESSES) either electronic or written comments regarding this 
document. It is only necessary to send one set of comments. It is no 
longer necessary to send two copies of mailed comments. Identify 
comments with the docket number found in brackets in the heading of 
this document. Received comments may be seen in the Division of Dockets 
Management between 9 a.m. and 4 p.m., Monday through Friday.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
either

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm,
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm,
http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/default.htm,
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm, or http://www.regulations.gov.

    Dated: December 27, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-33550 Filed 12-29-11; 8:45 am]
BILLING CODE 4160-01-P