[Federal Register Volume 80, Number 221 (Tuesday, November 17, 2015)]
[Notices]
[Pages 71810-71811]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-29281]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-D-0529]


Organ-Specific Warnings: Internal Analgesic, Antipyretic, and 
Antirheumatic Drug Products for Over-the-Counter Human Use--Labeling 
for Products That Contain Acetaminophen; Guidance for Industry; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a guidance for industry entitled ``Organ-Specific 
Warnings: Internal Analgesic, Antipyretic, and Antirheumatic Drug 
Products for Over-the-Counter Human Use--Labeling for Products That 
Contain Acetaminophen.'' The guidance is intended to inform 
manufacturers of certain nonprescription (also referred to as over-the-
counter or OTC) internal analgesic, antipyretic, and antirheumatic 
(IAAA) drug products that contain acetaminophen of the circumstances 
for which FDA does not intend to object to the inclusion of a liver 
warning that differs from that required under FDA regulations, provided 
the warning appears as described in the guidance.

DATES: Submit either electronic or written comments on Agency guidances 
at any time.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2012-D-0529 for ``Organ-Specific Warnings: Internal Analgesic, 
Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Human 
Use--Labeling for Products That Contain Acetaminophen Guidance for 
Industry.'' Received comments will be placed in the docket and, except 
for those submitted as ``Confidential Submissions,'' publicly viewable 
at http://www.regulations.gov or at the Division of Dockets Management 
between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. If you do not 
wish your name and contact information to be made publicly available, 
you can provide this information on the cover sheet and not in the body 
of your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Division of Dockets Management, 5630 Fishers 
Lane, rm. 1061, Rockville, MD 20852.
    Submit written requests for single copies of this guidance to the 
Division of Drug Information, Center for Drug Evaluation and Research, 
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale 
Building, 4th Floor, 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 guidance document.

FOR FURTHER INFORMATION CONTACT: Emily Baker, Office of Unapproved 
Drugs and Labeling Compliance, Center for Drug Evaluation and Research, 
Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, 
MD 20993-0002, 301-796-7524, [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Organ-Specific Warnings: Internal Analgesic, Antipyretic, 
and Antirheumatic Drug Products for Over-the-Counter Human Use--
Labeling for Products That Contain Acetaminophen.'' In the Federal 
Register of December 26, 2006 (71 FR 77314), FDA published a proposed 
rule on organ-specific warnings and related labeling for OTC IAAA drug 
products. In the Federal Register of April 29, 2009 (74 FR 19385), FDA 
published the final rule (2009 final rule). In the Federal Register of 
November 25, 2009 (74 FR 61512), FDA published a technical amendment to 
clarify several provisions in response to industry feedback. The 2009 
final rule, as amended, changed some of the labeling requirements for 
OTC IAAA drug products to inform consumers about the risk of liver 
injury when using acetaminophen and the risk of stomach bleeding when 
using nonsteroidal anti-

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inflammatory drugs. It went into effect April 29, 2010.
    Under that rule, the labeling for OTC IAAA products that contain 
acetaminophen and are labeled for adults only must include the liver 
warning described below. Similarly, the labeling for OTC IAAA products 
that contain acetaminophen and are labeled for adults and children 
under 12 year of age must include a similar liver warning described 
below.
    Adults Only (Sec.  201.326(a)(1)(iii)(A) (21 CFR 
201.326(a)(1)(iii)(A))):

    Liver warning: This product contains acetaminophen. Severe liver 
damage may occur if you take  more than [insert maximum 
number of daily dosage units] in 24 hours, which is the maximum 
daily amount [optional: ``for this product'']  with other 
drugs containing acetaminophen  3 or more alcoholic drinks 
every day while using this product.

    Adults and children under 12 years of age (Sec.  
201.326(a)(1)(v)(A) (21 CFR 201.326(a)(1)(v)(A))):

    Liver warning: This product contains acetaminophen. Severe liver 
damage may occur if  adult takes more than [insert maximum 
number of daily dosage units] in 24 hours, which is the maximum 
daily amount [optional: ``for this product'']  child takes 
more than 5 doses in 24 hours  taken with other drugs 
containing acetaminophen  adult has 3 or more alcoholic 
drinks every day while using this product.

    Although the currently proposed maximum daily dose of acetaminophen 
is 4,000 milligrams (mg), some OTC IAAA products that contain 
acetaminophen have directions for use that provide a maximum daily dose 
of acetaminophen for that product that is less than 4,000 mg. For 
example, for some OTC IAAA drug products that contain both 
acetaminophen and one or more other active ingredients, the maximum 
number of daily dosage units might be limited by an active ingredient 
other than acetaminophen, which could result in a maximum daily dose of 
acetaminophen that is less than 4,000 mg for that product. The optional 
statement, ``for this product,'' in the first bullet of the liver 
warning is intended to address these situations by clarifying that the 
maximum number of daily dosage units for a product might not reflect 
the maximum daily dose of acetaminophen.
    However, the Agency understands that in certain circumstances, 
despite this optional statement, the wording of the first bullet in the 
warnings shown above might be interpreted as indicating that severe 
liver damage is associated with a total daily dose of acetaminophen 
that is less than 4,000 mg. This suggestion is not the intent of the 
regulation. To address this potential confusion, the Agency does not 
intend to object to the inclusion of a liver warning that differs from 
that required under Sec.  201.326(a)(1)(iii)(A) and Sec.  
201.326(a)(1)(v)(A), provided the warning appears as described in the 
guidance.
    In the Federal Register of July 5, 2012 (77 FR 39710), FDA 
published a draft guidance entitled ``Organ-Specific Warnings: Internal 
Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-
Counter Human Use--Labeling for Products That Contain Acetaminophen.'' 
The July 2012 draft guidance gave interested persons an opportunity to 
submit comments through September 4, 2012. We have made changes to the 
guidance in response to comments received and have clarified the 
information in section III of the draft guidance.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on Organ-Specific Warnings: Internal Analgesic, 
Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Human 
Use--Labeling for Products That Contain Acetaminophen. It does not 
establish any rights for any person and is not binding on FDA or the 
public. You can use an alternative approach if it satisfies the 
requirements of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1965

    The recommendations in this guidance are not subject to review by 
the Office of Management and Budget because they do not constitute a 
``collection of information'' under the Paperwork Reduction Act of 1995 
(44 U.S.C. 3501 et seq.). Rather, the labeling statements are a 
``public disclosure of information originally supplied by the Federal 
government to the recipient for the purpose of disclosure to the 
public'' (5 CFR 1320.3(c)(2)).

III. Electronic Access

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

    Dated: November 12, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-29281 Filed 11-16-15; 8:45 am]
 BILLING CODE 4164-01-P