Draft Guidance for Industry on Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices; Availability, 82303-82306 [2011-33550]
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Federal Register / Vol. 76, No. 251 / Friday, December 30, 2011 / Notices
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FOR FURTHER INFORMATION CONTACT:
Kristiana Brugger, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, rm. 6262,
Silver Spring, MD 20993–0002, (301)
796–3601.
SUPPLEMENTARY INFORMATION: In 1984,
Congress enacted the Drug Price
Competition and Patent Term
Restoration Act of 1984 (Pub. L. 98–417)
(the 1984 amendments), which
authorized the approval of duplicate
versions of drug products under an
ANDA procedure. ANDA applicants
must, with certain exceptions, show that
the drug for which they are seeking
approval contains the same active
ingredient in the same strength and
dosage form as the ‘‘listed drug,’’ which
is a version of the drug that was
previously approved. ANDA applicants
do not have to repeat the extensive
clinical testing otherwise necessary to
gain approval of a new drug application
(NDA). The only clinical data required
in an ANDA are data to show that the
drug that is the subject of the ANDA is
bioequivalent to the listed drug.
The 1984 amendments include what
is now section 505(j)(7) of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C.
355(j)(7)), which requires FDA to
publish a list of all approved drugs.
FDA publishes this list as part of the
‘‘Approved Drug Products With
Therapeutic Equivalence Evaluations,’’
which is known generally as the
‘‘Orange Book.’’ Under FDA regulations,
drugs are removed from the list if the
Agency withdraws or suspends
approval of the drug’s NDA or ANDA
for reasons of safety or effectiveness or
if FDA determines that the listed drug
was withdrawn from sale for reasons of
safety or effectiveness (21 CFR 314.162).
A person may petition the Agency to
determine, or the Agency may
determine on its own initiative, whether
a listed drug was withdrawn from sale
for reasons of safety or effectiveness.
This determination may be made at any
time after the drug has been withdrawn
from sale, but must be made prior to
approving an ANDA that refers to the
listed drug (§ 314.161 (21 CFR 314.161)).
FDA may not approve an ANDA that
does not refer to a listed drug.
HYCODAN (hydrocodone bitartrate
and homatropine methylbromide)
tablets, 5 mg/1.5 mg, and HYCODAN
(hydrocodone bitartrate and
homatropine methylbromide) oral
solution, 5 mg/5 mL and 1.5 mg/5 mL,
are the subject of NDA 05–213, held by
Endo Pharmaceuticals, and initially
approved on March 23, 1943. In 1982,
a Drug Efficacy Study Implementation
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review concluded that HYCODAN
syrup, tablets, and powder were
effective ‘‘for the symptomatic relief of
cough.’’ (47 FR 23809, June 1, 1982).
Subsequently, the sponsor submitted an
NDA for HYCODAN (hydrocodone
bitartrate and homatropine
methylbromide) tablets, 5 mg/1.5 mg,
and HYCODAN (hydrocodone bitartrate
and homatropine methylbromide) oral
solution, 5 mg/5 mL and 1.5 mg/5 mL,
which was approved on July 26, 1988.
HYCODAN is indicated for the
symptomatic relief of cough in adults
and children 6 years of age and older.
In a letter dated January 4, 2008, Endo
Pharmaceuticals notified FDA that
HYCODAN (hydrocodone bitartrate and
homatropine methylbromide) tablets, 5
mg/1.5 mg, were being discontinued,
and FDA moved the drug product to the
‘‘Discontinued Drug Product List’’
section of the Orange Book. Vintage
Pharmaceutical, Inc., submitted a
citizen petition dated October 15, 2008
(Docket No. FDA–2008–P–0555), under
21 CFR 10.30, requesting that the
Agency determine whether HYCODAN
(hydrocodone bitartrate and
homatropine methylbromide) tablets, 5
mg/1.5 mg, were withdrawn from sale
for reasons of safety or effectiveness.
Although the citizen petition did not
request it, FDA has determined, on its
own initiative, whether the oral solution
dosage form was withdrawn for safety or
effectiveness reasons.
After considering the citizen petition
and reviewing Agency records and
based on the information we have at this
time, FDA has determined under
§ 314.161 that HYCODAN (hydrocodone
bitartrate and homatropine
methylbromide) tablets, 5 mg/1.5 mg,
and HYCODAN (hydrocodone bitartrate
and homatropine methylbromide) oral
solution, 5 mg/5 mL and 1.5 mg/5 mL,
were not withdrawn for reasons of
safety or effectiveness. The petitioner
has identified no data or other
information suggesting that HYCODAN
(hydrocodone bitartrate and
homatropine methylbromide) tablets, 5
mg/1.5 mg, or HYCODAN (hydrocodone
bitartrate and homatropine
methylbromide) oral solution, 5 mg/5
mL and 1.5 mg/5 mL, were withdrawn
for reasons of safety or effectiveness. We
have carefully reviewed our files for
records concerning the withdrawal of
HYCODAN (hydrocodone bitartrate and
homatropine methylbromide) tablets, 5
mg/1.5 mg, and HYCODAN
(hydrocodone bitartrate and
homatropine methylbromide) oral
solution, 5 mg/5 mL and 1.5 mg/5 mL,
from sale. We have also independently
evaluated relevant literature and data
for possible postmarketing adverse
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82303
events. We have found no information
that would indicate that these products
were withdrawn from sale for reasons of
safety or effectiveness.
Accordingly, the Agency will
continue to list HYCODAN
(hydrocodone bitartrate and
homatropine methylbromide) tablets, 5
mg/1.5 mg, and HYCODAN
(hydrocodone bitartrate and
homatropine methylbromide) oral
solution, 5 mg/5 mL and 1.5 mg/5 mL,
in the ‘‘Discontinued Drug Product List’’
section of the Orange Book. The
‘‘Discontinued Drug Product List’’
delineates, among other items, drug
products that have been discontinued
from marketing for reasons other than
safety or effectiveness. ANDAs that refer
to HYCODAN (hydrocodone bitartrate
and homatropine methylbromide)
tablets, 5 mg/1.5 mg, or HYCODAN
(hydrocodone bitartrate and
homatropine methylbromide) oral
solution, 5 mg/5 mL and 1.5 mg/5 mL,
may be approved by the Agency as long
as they meet all other legal and
regulatory requirements for the approval
of ANDAs. If FDA determines that
labeling for this drug product should be
revised to meet current standards, the
Agency will advise ANDA applicants to
submit such labeling.
Dated: December 22, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011–33549 Filed 12–29–11; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2011–D–0868]
Draft Guidance for Industry on
Responding to Unsolicited Requests
for Off-Label Information About
Prescription Drugs and Medical
Devices; Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
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
SUMMARY:
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Federal Register / Vol. 76, No. 251 / Friday, December 30, 2011 / Notices
medical devices can respond to
unsolicited requests for information
about unapproved or uncleared
indications or conditions of use (offlabel information) related to their FDAapproved or cleared products. This draft
guidance updates and clarifies FDA’s
policies on unsolicited requests for offlabel 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 https://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.
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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 offlabel 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
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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 offlabel 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
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Federal Register / Vol. 76, No. 251 / Friday, December 30, 2011 / Notices
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
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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 nonbiased 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,
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82305
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, FDAapproved 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
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document for non-public responses to
unsolicited requests).
2. Representatives who provide public
responses to unsolicited requests for offlabel 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, FDAapproved 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 nonpublic 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
Draft guidance on responding to unsolicited
requests for off-label information
Number of
respondents
Responses to non-public and public unsolicited requests .....................................................................
1 There
Number of
responses per
respondent
400
Total annual
responses
100
Average burden
per response
40,000
4
Total hours
160,000
are no capital costs or operating and maintenance costs associated with this collection of information.
TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1
Draft guidance on responding to unsolicited
requests for off-label information
Number of
recordkeepers
Records related to responses to non-public and
public unsolicited requests .....................................
1 There
400
Total annual
records
100
Average
burden per
recordkeeping
40,000
.25
Total hours
10,000
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
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Jkt 226001
[FR Doc. 2011–33550 Filed 12–29–11; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2011–D–0872]
Draft Guidance for Industry on Use of
Histology in Biomarker Qualification
Studies; Availability
Food and Drug Administration,
HHS.
ACTION:
https://www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm,
https://www.fda.gov/BiologicsBlood
Vaccines/GuidanceCompliance
RegulatoryInformation/default.htm,
https://www.fda.gov/AnimalVeterinary/
GuidanceComplianceEnforcement/
GuidanceforIndustry/default.htm,
https://www.fda.gov/MedicalDevices/
DeviceRegulationandGuidance/
GuidanceDocuments/default.htm, or
https://www.regulations.gov.
VerDate Mar<15>2010
Dated: December 27, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
AGENCY:
Persons with access to the Internet
may obtain the document at either
srobinson on DSK4SPTVN1PROD with NOTICES
Number of
records per
recordkeeper
Notice.
The Food and Drug
Administration (FDA) is announcing the
availability of a draft guidance for
industry entitled ‘‘Use of Histology in
Biomarker Qualification Studies.’’ This
guidance is intended to assist sponsors
that conduct biomarker qualification
studies for which histology is a
reference standard. This guidance
discusses the processes that should be
considered to ensure the quality and
integrity of histology data in biomarker
studies, and outlines the scientific
standards for histology used in
SUMMARY:
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biomarker characterization and
qualification. The recommendations in
this guidance are intended for studies in
biomarker qualification designated to
justify the proposed context of use,
where scientifically rigorous evaluation
of biomarker performance in relation to
histologic changes is essential. The
principles outlined in this guidance are
also applicable to exploratory biomarker
studies.
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 comment 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 either electronic or written
comments concerning the proposed
collection of information by February
28, 2012.
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. Send
one self-addressed adhesive label to
assist that office in processing your
requests. See the SUPPLEMENTARY
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]]>Agencies
[Federal Register Volume 76, Number 251 (Friday, December 30, 2011)]
[Notices]
[Pages 82303-82306]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-33550]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2011-D-0868]
Draft Guidance for Industry on Responding to Unsolicited Requests
for Off-Label Information About Prescription Drugs and Medical Devices;
Availability
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 https://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
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm,
https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm,
https://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/default.htm,
https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm, or https://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
