
[Federal Register Volume 79, Number 41 (Monday, March 3, 2014)]
[Notices]
[Pages 11793-11796]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-04560]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-D-0053]


Revised Draft Guidance for Industry on Distributing Scientific 
and Medical Publications on Unapproved New Uses--Recommended Practices; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a revised draft guidance for industry entitled 
``Distributing Scientific and Medical Publications on Unapproved New 
Uses--Recommended Practices.'' This draft guidance revises the final 
guidance titled ``Good Reprint Practices for the Distribution of 
Medical Journal Articles and Medical or Scientific Reference 
Publications on Unapproved New Uses of Approved Drugs and Approved or 
Cleared Medical Devices'' published in January 2009. The revised draft 
guidance provides guidance on FDA's current thinking on recommended 
practices for drug or medical device manufacturers and their 
representatives to follow when distributing to health care 
professionals or health care entities scientific or medical journal 
articles, scientific or medical reference texts, or clinical practice 
guidelines ((CPGs); all three collectively referred to as ``scientific 
and medical publications'') that discuss unapproved new uses for 
approved drugs or approved or cleared medical devices marketed in the 
United States.

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this draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by May 2, 2014. Submit either electronic or written comments 
on the proposed collection of information by May 2, 2014.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 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; 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 the 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 prescription drugs: Bryant Godfrey, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave, Bldg. 51, Rm. 3258, Silver Spring, MD 20993-0002, 301-
796-1200.
    Regarding prescription 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 medical devices: Deborah Wolf, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 3414, Silver Spring, MD 20993-0002, 301-796-5732.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a revised draft guidance for 
industry entitled ``Distributing Scientific and Medical Publications on 
Unapproved New Uses--Recommended Practices.'' This draft guidance 
describes recommended practices for drug or medical device 
manufacturers or their representatives to follow when distributing to 
health care professionals or health care entities scientific and 
medical publications that discuss unapproved new uses of approved drugs 
or approved or cleared medical devices.
    In January 2009, FDA published a final guidance titled ``Good 
Reprint Practices for the Distribution of Medical Journal Articles and 
Medical or Scientific Reference Publications on Unapproved New Uses of 
Approved Drugs and Approved or Cleared Medical Devices,'' which set 
forth the Agency's thinking as of that time regarding the dissemination 
by manufacturers of medical journal articles and scientific or medical 
reference publications that discuss unapproved or uncleared uses of 
medical products.\1\ FDA received comments to the docket for the 2009 
guidance, including submissions requesting clarification of how the 
principles set forth in the 2009 guidance would apply to medical 
textbooks and potential changes to those principles.
---------------------------------------------------------------------------

    \1\ Please visit http://www.regulations.gov and enter docket 
number FDA-2008-D-0053.
---------------------------------------------------------------------------

    In July 2011 and September 2013, FDA received citizen petitions, 
filed on behalf of multiple prescription drug and medical device 
manufacturers, that include several requests related to FDA's approach 
to the distribution of scientific and medical information reflecting 
unapproved or uncleared uses, specifically including CPGs.\2\ FDA 
continues to consider the specific requests made in the citizen 
petitions, which include requests for issuance or revision of 
regulations, and has not yet reached a final determination on those 
petitions.
---------------------------------------------------------------------------

    \2\ Please visit http://www.regulations.gov and enter docket 
numbers FDA-2011-P-0512 and FDA-2013-P-1079.
---------------------------------------------------------------------------

    At the same time, FDA continues actively to review, analyze, and 
develop approaches to a variety of topics of interest to industry and 
others, including issues raised in the petition. As part of this 
process, FDA is soliciting public comment on the draft guidance made 
available here. Similarly, as part of the Agency's ongoing efforts to 
address industry questions, FDA continues to solicit public input and 
consider approaches with respect to several related issues, including 
the following:
    (1) Further explaining ``scientific exchange.'' On December 28, 
2011, FDA issued a Federal Register notice (76 FR 81508) opening a 
docket and requesting comments and information related to ``scientific 
exchange.'' Comments were submitted to Docket No. FDA-2011-N-0912. FDA 
is reviewing those comments and considering how that information may 
inform future Agency action related to its policies on communications 
and activities related to unapproved or uncleared uses of marketed 
drugs and devices, as well as communications and activities related to 
use of products that are not yet legally marketed for any use.

[[Page 11794]]

    (2) Developing guidance on the issue of manufacturer responses to 
unsolicited requests for information relating to unapproved or 
uncleared uses. In December 2011, FDA issued a draft guidance entitled 
``Responding to Unsolicited Requests for Off-Label Information About 
Prescription Drugs and Medical Devices.'' FDA is currently considering 
comments on that draft guidance to inform its further action on this 
topic.
    (3) Considering draft guidance on industry interactions with 
formulary committees, payors, and similar entities. This includes 
clarifying the Agency's interpretation of several terms included in 
section 114 of the Food and Drug Administration Modernization Act of 
1997 (Pub. L. 105-115) and the Agency's recommendations for evidentiary 
support for health care economic information included in promotional 
materials disseminated to formulary committees and similar entities.
    Among the other issues under evaluation, FDA is considering a range 
of options for responding to questions about industry participation in 
scientific discussions and for addressing industry dissemination of new 
scientific information related to approved or cleared uses of marketed 
drugs and devices.
    FDA is soliciting public comment on the revised draft guidance made 
available here, which presents recommended practices for drug or 
medical device manufacturers and their representatives to follow if 
they choose to distribute to health care professionals or health care 
entities scientific or medical journal articles, scientific or medical 
reference texts, or CPGs that discuss unapproved or uncleared uses of 
legally marketed drugs and devices. If the recommended practices are 
followed, FDA does not intend to use distribution of these publications 
as evidence of the manufacturer's intent that the product be used for 
an unapproved new use. FDA is issuing the revised guidance in draft 
form to enable the public to provide comments on the proposed 
recommendations.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115) and, when finalized, will 
represent the Agency's current thinking on the topic. 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

    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 that 
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 for each proposed collection of 
information before submitting the collection to OMB for approval. To 
comply with this requirement, FDA is publishing this notice of the 
proposed collection of information set forth in this document.
    With respect to the collection of information associated with this 
draft guidance, FDA invites comments on the following topics: (1) 
Whether the proposed information collected is necessary for the proper 
performance of FDA's functions, including whether the information will 
have practical utility; (2) the accuracy of FDA's estimated burden of 
the proposed information collected, 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: Distributing Scientific and Medical Publications on 
Unapproved New Uses--Recommended Practices.
    Description of Respondents: Respondents to this collection of 
information are manufacturers and distributors (firms) of approved drug 
products or approved/cleared medical devices.
    Burden Estimate: The draft guidance pertains to the distribution of 
scientific and medical publications by FDA-regulated industry that 
discuss unapproved new uses for approved or cleared products. The draft 
guidance explains that FDA's current position is that if a manufacturer 
follows the recommendations as described in the draft guidance, FDA 
does not intend to use the distribution of the scientific and medical 
publications as evidence of intent that the product be used for an 
unapproved new use. Because the draft guidance recommends that 
scientific and medical publications reflecting unapproved or uncleared 
uses that are distributed have certain characteristics, and that 
certain other information be distributed with them, the guidance 
recommends a ``third-party disclosure'' that constitutes a ``collection 
of information'' under the PRA.
    The draft guidance provides recommendations regarding the 
characteristics of scientific and medical publications that companies 
may choose to distribute. Elaborated in more detail in the draft 
guidance, these characteristics in general include that these 
publications be from journals, scientific or medical reference texts, 
and CPGs that are produced by independent sources and meet criteria for 
professional/peer review; be based on specified types of scientific 
evidence; and be complete, unabridged, and without highlighting or 
characterization by the manufacturer. In addition, the draft guidance 
provides recommendations for additional information to be supplied with 
the publications.
    Specifically, the draft guidance recommends the following:
    Scientific or medical journal articles should:
     Be disseminated with the approved labeling or, in the case 
of a medical device reviewed under section 510(k) of the FD&C Act (21 
U.S.C. 360(k)), labeling for the indications in the product's cleared 
indications for use statement, for each of the manufacturer's products 
that is included in the distributed article.
     Be disseminated with a comprehensive bibliography, when 
such information exists, of publications discussing adequate and well-
controlled clinical studies published in scientific journals, medical 
journals, or scientific texts about the use of the drug or medical 
device covered by the information disseminated (unless the information 
already includes such a bibliography).
     Be disseminated with a representative publication, when 
such information exists, that reaches contrary or different conclusions 
regarding the unapproved use--especially when the conclusions of 
articles to be disseminated have been specifically called into question 
by another publication.
     Be accompanied by a prominently displayed and permanently 
affixed statement disclosing:
    [cir] The drug(s) or device(s) included in the journal reprint in 
which the manufacturer has an interest;
    [cir] That some or all uses of the manufacturer's drugs or devices 
described in the information have not

[[Page 11795]]

been approved or cleared by FDA, as applicable to the described drug(s) 
or device(s);
    [cir] Any author known to the manufacturer as having a financial 
interest in the manufacturer or in a product of the manufacturer that 
is included in the journal article, or who is receiving compensation 
from the manufacturer, along with the affiliation of the author, to the 
extent known by the manufacturer, and the nature and amount of any such 
financial interest of the author or compensation received by the author 
from the manufacturer;
    [cir] Any person known to the manufacturer who has provided funding 
for the study;
    [cir] All significant risks or safety concerns associated with the 
unapproved use(s) of the manufacturer's product(s) discussed in the 
journal article that are known to the manufacturer but not discussed in 
the journal article.
    Scientific or medical reference texts should:
     When distributed in their entirety by a manufacturer:
    [cir] Contain a prominently displayed and permanently affixed 
statement identifying the distributing manufacturer and disclosing that 
some of the uses for drugs and/or devices described in the reference 
text might not be approved or cleared by FDA. The statement should also 
disclose that the author(s) of some chapters also might have a 
financial interest in the manufacturer or its products, unless the 
manufacturer has verified that none of the authors for the reference 
text has a financial interest in the manufacturer or a product being 
written about.\3\ This statement should be placed by sticker, stamp, or 
other similar means on the front cover of the textbook;
---------------------------------------------------------------------------

    \3\ If a reference text is distributed in its entirety with this 
statement affixed, manufacturers are not expected to have reviewed 
every element of the reference text to identify discussions of off-
label uses of their products. However, even where an entire 
reference text is being distributed, manufacturers should determine 
whether one or more individual chapters of that reference text 
devote primary substantive discussion to an individual product or 
products of the manufacturer distributing it, in order to determine 
whether dissemination of product labeling is recommended.
---------------------------------------------------------------------------

    [cir] In situations where a reference text is distributed in its 
entirety but one or more individual chapters of that reference text 
devote primary substantive discussion to an individual product or 
products of the manufacturer distributing it, be disseminated with the 
approved product labeling for each such product or, in the case of a 
medical device reviewed under section 510(k) of the FD&C Act, labeling 
for the indications in the product's cleared indications for use 
statement.
     If, in lieu of an entire scientific or medical reference 
text, a manufacturer distributes an individual chapter(s) that includes 
information on unapproved/uncleared uses of the manufacturer's 
product(s), the chapter(s) should:
    [cir] When necessary to provide context, be disseminated with other 
unaltered/unabridged chapters extracted directly from the same 
scientific or medical reference text, such as chapters which provide 
related or supportive information;
    [cir] Contain a prominently displayed and permanently affixed 
statement identifying the distributing manufacturer and disclosing: (1) 
The drug(s) or device(s) addressed in the individual chapter(s) in 
which the manufacturer has an interest; (2) that some or all uses of 
the manufacturer's drugs and/or devices described in the ensuing 
information have not been approved or cleared by FDA, as applicable to 
the described drug(s) or medical device(s); (3) any author known to the 
manufacturer as having a financial interest in the manufacturer or in a 
product of the manufacturer that is included in the individual 
chapter(s), or who is receiving compensation from the manufacturer, 
along with the affiliation of the author, to the extent known by the 
manufacturer, and the nature and amount of any such financial interest 
of the author or compensation received by the author from the 
manufacturer; and (4) all significant risks or safety concerns 
associated with the unapproved use(s) of the manufacturer's products 
discussed in the individual chapter(s) that are known to the 
manufacturer but not discussed in the chapter(s);
    [cir] Be disseminated with the approved labeling, or, in the case 
of a medical device reviewed under section 510(k) of the FD&C Act, 
labeling for the indications in the cleared indications for use 
statement, for each of the manufacturer's products that are included in 
the distributed chapter(s).
    CPGs should:
     When distributed by a manufacturer in their entirety:
    [cir] Contain a prominently displayed and permanently affixed 
statement identifying the distributing manufacturer and disclosing that 
some of the uses of drugs and/or devices described in the CPG might not 
be approved or cleared by FDA. The statement should also disclose that 
the author(s) of some sections might have a financial interest in the 
manufacturer or its products, unless the manufacturer has verified that 
none of the authors for the CPG has a financial interest in the 
manufacturer or a product being written about. This statement should be 
placed by sticker, stamp, or other similar means on the front page of 
the CPG.
    [cir] In situations where a CPG is distributed in its entirety but 
one or more individual sections of that CPG devotes primary substantive 
discussion to an individual product or products of the manufacturer 
distributing it, be disseminated with the approved product labeling for 
each such product or, in the case of a medical device reviewed under 
section 510(k) of the FD&C Act, labeling for the indications in the 
product's cleared indications for use statement.
     If, in lieu of an entire CPG, a manufacturer distributes 
an individual section(s) that includes information on unapproved/
uncleared uses of the manufacturer's product(s), the section(s) should:
    [cir] When necessary to provide context, be disseminated with other 
unaltered/unabridged sections extracted directly from the same CPG, 
such as sections which provide related or supportive information;
    [cir] Contain a prominently displayed and permanently affixed 
statement identifying the distributing manufacturer and disclosing: (1) 
The drug(s) or device(s) addressed in the individual section(s) in 
which the manufacturer has an interest; (2) that some or all uses of 
the manufacturer's drugs and/or devices described in the attached 
information have not been approved or cleared by FDA, as applicable to 
the described drug(s) or medical device(s); (3) any author known to the 
manufacturer as having a financial interest in the manufacturer or in a 
product of the manufacturer that is included in the individual 
section(s), or who is receiving compensation from the manufacturer, 
along with the affiliation of the author, to the extent known by the 
manufacturer, and the nature and amount of any such financial interest 
of the author or compensation received by the author from the 
manufacturer; and (4) all significant risks or safety concerns 
associated with the unapproved use(s) of the manufacturer's products 
discussed in the individual section(s) that are known to the 
manufacturer but not discussed in the section(s).
    [cir] Be disseminated with the approved labeling, or, in the case 
of a medical device reviewed under section 510(k) of the FD&C Act, 
labeling for the indications in the cleared indications for use 
statement, for each of the manufacturer's products that is included in 
the distributed section(s).

[[Page 11796]]

    FDA estimates that approximately 400 firms (``number of 
respondents'' in table 1) distribute scientific and medical 
publications that discuss unapproved new uses for FDA-approved or -
cleared products. FDA also estimates that each firm would include some 
or all of the additional information described previously when 
distributing annually a total of approximately 40,000 scientific or 
medical journal articles, scientific or medical reference texts, or 
CPGs (``total annual disclosures'' in table 1) that discuss unapproved 
new uses for FDA-approved or -cleared products. FDA estimates that it 
will take each firm approximately 4 hours (``hours per disclosure'' in 
table 1) to make the disclosures recommended in this draft guidance.

                           Table 1--Estimated Annual Third Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
 Draft guidance on distributing
     scientific and medical          Number of        Number of      Total annual       Average
  information on unapproved new     respondents   disclosures  per    disclosures     burden per     Total hours
              uses                                   respondent                       disclosure
----------------------------------------------------------------------------------------------------------------
Distribution of scientific and              400               100          40,000               4       160,000
 medical information on
 unapproved new uses............
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

III. Comments

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of 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, and will be posted to the docket at http://www.regulations.gov.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm, http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm, or http://www.regulations.gov.

    Dated: February 25, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-04560 Filed 2-28-14; 8:45 am]
BILLING CODE 4160-01-P


