
[Federal Register Volume 79, Number 112 (Wednesday, June 11, 2014)]
[Notices]
[Pages 33569-33572]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-13569]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-D-0758]


Draft Guidance for Industry on Distributing Scientific and 
Medical Publications on Risk Information for Approved Prescription 
Drugs and Biological Products--Recommended Practices; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled 
``Distributing Scientific and Medical Publications on Risk Information 
for Approved Prescription Drugs and Biological Products--Recommended 
Practices.'' This guidance describes FDA's current thinking on 
recommended practices for drug manufacturers and their representatives 
to follow when distributing to health care professionals or health care 
entities scientific or medical journal articles that discuss new risk 
information for approved prescription drugs for human use, including 
drugs licensed as biological products, and approved animal drugs. The 
recommendations in this draft guidance are intended to address issues 
specific to the distribution of new information about risks associated 
with a drug that further characterizes risks identified in the approved 
labeling.

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draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by August 25, 2014. Submit written comments on the proposed 
collection of information by August 11, 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ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 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; 
Office of Communication, Outreach and Development, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002; or to 
Communications Staff (HFV-12), Center

[[Page 33570]]

for Veterinary Medicine, Food and Drug Administration, 7519 Standish 
Pl., Rockville, MD 20855. 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 prescription drugs: Lauren Wedlake, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6328, Silver Spring, MD 20993-0002, 301-
796-2500.
    Regarding prescription biological products: Stephen Ripley, Center 
for Biologics Evaluation and Research, Food and Drug Administration, 
10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-
0002, 240-402-7911.
    Regarding animal drugs: Dorothy McAdams, Center for Veterinary 
Medicine (HFV-216), 7519 Standish Pl., Rockville, MD 20855, 240-453-
6802.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Distributing Scientific and Medical Publications on Risk 
Information for Approved Prescription Drugs and Biological Products--
Recommended Practices.'' In February 2014, FDA issued a draft guidance 
entitled ``Distributing Scientific and Medical Publications on 
Unapproved New Uses--Recommended Practices'' to clarify the Agency's 
position on manufacturer dissemination of scientific or medical 
publications--including scientific or medical journal articles, 
scientific or medical reference texts, and clinical practice 
guidelines--that include information on unapproved new uses of the 
manufacturer's products. Stakeholders have raised questions regarding 
the Agency's position on manufacturer dissemination of new scientific 
or medical information about safety information contained in the 
labeling for approved drugs. Because this concerns dissemination of new 
risk information related to approved uses of a drug, this issue is 
distinct from the dissemination of information on unapproved new uses 
of approved drugs. In response to those questions, the Agency is 
issuing this draft guidance to clarify and solicit public comments on 
the Agency's position on manufacturer dissemination of new risk 
information regarding lawfully marketed drugs for approved uses to 
health care professionals or health care entities.
    FDA recognizes that the safety profile of a drug evolves throughout 
its lifecycle as the extent of exposure to the product increases and 
that it can be helpful for health care practitioners to receive 
significant new risk information about an approved product in a timely 
manner. FDA anticipates that the earliest distribution of new risk 
information will generally involve distribution of recently published 
studies, as opposed to textbooks or clinical practice guidelines. 
Accordingly, FDA is providing guidance for manufacturers that choose to 
distribute new risk information in the form of a reprint or digital 
copy of a published study.
    FDA believes that recommendations specific to the distribution of 
risk information are needed for two reasons:
     In general, there are differences in the purpose, nature, 
and reliability of the evidence used to determine the effectiveness of 
a drug (e.g., to support a new intended use) and the evidence that is 
the basis for a product's risk assessment. Therefore, FDA believes 
guidance is needed to address the spectrum of data sources that could 
be appropriate for distribution to provide new risk information.
     New risk information may contradict or otherwise deviate 
from the risk information in the approved labeling, which may cause 
confusion or otherwise contribute to patient harm. If the new 
information is unreliable or presented without the appropriate context, 
it could influence prescribing decisions or patient monitoring in a 
manner that could harm patients. Therefore, FDA is proposing 
recommendations for study or analysis and distribution criteria to help 
ensure that new risk information that rebuts, mitigates, or refines 
risk information in approved labeling meets appropriate standards for 
reliability and is presented with appropriate disclosure of its 
limitations.
    The guidance is being issued in draft to enable public comment on 
the proposed recommendations.
    In light of emerging case law, in particular the case law involving 
the First and Fifth Amendments of the United States Constitution, FDA 
is currently engaged in a comprehensive review of its regulations and 
guidance documents in an effort to harmonize the fundamental public 
health interests underlying FDA's mission and statutory framework with 
interests in the dissemination of truthful and non-misleading 
information. This draft guidance on distribution of risk information 
about approved prescription drugs and biological products is a part of 
that effort. This draft guidance does not address medical devices. FDA 
also plans to issue, by the end of the calendar year, additional 
guidance that addresses manufacturer responses to unsolicited requests, 
distributing scientific and medical information on unapproved new uses, 
manufacturer discussions regarding scientific information more 
generally, and distribution of health care economic information to 
formulary committees and similar entities.
    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 
``Distributing Scientific and Medical Publications on Risk Information 
for Approved Prescription Drugs and Biological Products--Recommended 
Practices.'' 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. This 
draft guidance also refers to previously approved collections of 
information found in FDA regulations.
    With respect to the following collection of information, FDA 
invites comments on these topics: (1) Whether the proposed information 
collected is necessary for the proper performance of FDA's functions, 
including whether the

[[Page 33571]]

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: Recommendations for Distributing Scientific and Medical 
Publications on Risk Information for Approved Prescription Drugs and 
Biological Products.
    Description of Respondents: Respondents to this collection of 
information are manufacturers of approved prescription drugs for human 
use, including drugs licensed as biological products, and approved 
animal drugs, and their representatives (firms).
    Burden Estimate: The draft guidance pertains to the distribution, 
by firms, of scientific and medical publications that discuss new risk 
information for approved prescription drugs for human use and approved 
animal drugs (including prescription, non-prescription, and Veterinary 
Feed Directive drugs) marketed in the United States. The draft guidance 
recommends that if firms choose to distribute scientific and medical 
publications reflecting new risk information, those publications should 
have certain characteristics and certain other information should be 
distributed with them. Accordingly, the guidance recommends a ``third-
party disclosure'' that constitutes a ``collection of information'' 
under the PRA.
    If firms choose to distribute new risk information that rebuts, 
mitigates, or refines risk information in the approved labeling, and 
the information is in the form of a reprint or digital copy of a 
published study, the guidance provides recommendations regarding the 
characteristics of those publications. Specifically, with respect to 
the data source:
     The study or analysis should meet accepted design and 
other methodologic standards for the type of study or analysis (e.g., 
provides a clear description of the hypothesis tested, acknowledges and 
accounts for potential bias and multiplicity) and should be 
sufficiently well-designed and informative to merit consideration in 
assessing the implications of a risk.
     To rebut a prior determination (reflected in the approved 
labeling) that there is some basis to believe there is causal 
relationship between the drug and the occurrence of an adverse event, 
or to otherwise mitigate a described risk, the study or analysis should 
also be at least as persuasive as the data sources that underlie the 
existing risk assessment of causality, severity, and/or incidence of 
the adverse reaction as reflected in approved labeling (e.g., data from 
a new controlled trial designed to estimate the relative risk of the 
event, a pharmacoepidemiologic study that is capable of reliably 
estimating the relative risk, or a rigorous meta-analysis of all 
relevant data from new and existing controlled trials).
     The conclusions of the study or analysis should give 
appropriate weight and consideration to, and should be a fair 
characterization of, all relevant information in the safety database, 
including contrary or otherwise inconsistent findings. There is a broad 
spectrum of potential data sources that can contribute in some way to 
characterization of a product's safety; new risk information should be 
considered in light of all relevant existing information and integrated 
with that data to the extent possible.
     The study or analysis should be published in an 
independent, peer-reviewed journal.
    The draft guidance also makes recommendations with respect to the 
distribution of the reprint or digital copy, including the 
recommendation that a cover sheet accompany the reprint or digital copy 
that clearly and prominently discloses the following:
     The study design, critical findings, and significant 
methodologic or other limitations of the study or analysis that may 
limit the persuasiveness or scope of findings that rebut, mitigate, or 
refine risk information in the approved labeling. Limitations should be 
discussed in relation to the specific circumstances of the study and 
its conclusions about a risk.
     The information is not consistent with certain risk 
information in the approved labeling (should specifically identify the 
inconsistent information).
     FDA has not reviewed the data.
     Any financial interests or affiliations between the study 
author(s) and the firm.
    The reprint or digital copy should be accompanied by the approved 
labeling for the product, and when distributed, should be separate from 
any promotional material. Any statements made by a representative of 
the firm to a recipient concerning the reprint should be consistent 
with its content and the information in the disclosure cover sheet.
    Additionally, FDA notes in the draft guidance that the 
recommendations in the guidance do not change a firm's existing 
obligations to revise its approved labeling in accordance with 21 CFR 
201.56(a)(2), 314.70, 514.8(c) and 601.12. As described in this section 
of the document, this recommendation refers to previously approved 
collections of information found in FDA regulations. FDA estimates that 
approximately 500 firms annually distribute scientific and medical 
publications that discuss new risk information for approved 
prescription drugs. FDA also estimates that each firm would include 
some or all of the additional information described previously when 
distributing annually a total of approximately 4,250 scientific or 
medical journal articles that discuss new risk information for approved 
prescription drugs. FDA estimates that it will take each firm 
approximately 16 hours to make the disclosures recommended in this 
draft guidance, which includes the time needed to determine whether the 
article complies with the guidance recommendation on the 
characteristics of the scientific and medical publications that 
companies distribute, to determine financial conflicts of interest, to 
prepare the disclosure statements, and to attach the product labeling.

                           Table 1--Estimated Annual Third-Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
 Draft guidance on distributing
     scientific and medical
publications on risk information     Number of       Number of     Total annual   Average burden
 for approved prescription drugs    respondents     disclosures     disclosures   per disclosure    Total hours
    and biological products--                     per respondent
      recommended practices
----------------------------------------------------------------------------------------------------------------
Distribution of scientific and               500             8.5           4,250              16          68,000
 medical publications on risk
 information....................
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


[[Page 33572]]

    This draft guidance also refers to previously approved collections 
of information found in FDA regulations with respect to submitting 
supplements to approved applications. These collections of information 
are subject to review by OMB under the Paperwork Reduction Act of 1995 
(44 U.S.C. 3501-3502). The collection of information in 21 CFR 
201.56(a)(2) has been approved under OMB control number 0910-0572; in 
21 CFR 314.70 has been approved under OMB control number 0910-0001; in 
21 CFR 601.12 has been approved under OMB control number 0910-0338; and 
in 21 CFR 514.8(c) has been approved under OMB control number 0910-
0032.

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/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/default.htm, or http://www.regulations.gov.

    Dated: June 6, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-13569 Filed 6-10-14; 8:45 am]
BILLING CODE 4164-01-P


