
[Federal Register Volume 79, Number 195 (Wednesday, October 8, 2014)]
[Notices]
[Pages 60854-60855]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-23973]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-D-1473]


Over-the-Counter Pediatric Liquid Drug Products Containing 
Acetaminophen; Draft Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry entitled ``Over-the-
Counter Pediatric Liquid Drug Products Containing Acetaminophen.'' The 
draft guidance is intended to help drug manufacturers, packagers, and 
labelers minimize the risk to consumers of acetaminophen-related liver 
damage associated with the use of nonprescription, also known as over-
the-counter (OTC), acetaminophen-containing pediatric liquid drug 
products. This guidance provides recommendations for acetaminophen 
concentration, container labels and carton labeling, packaging of such 
products, and recommendations regarding any associated delivery 
devices. FDA's recommendations are designed to encourage safer use of 
these products by minimizing the potential for acetaminophen overdosing 
due to medication errors or accidental ingestion.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)), 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draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by December 8, 2014.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 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, 10001 New 
Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 
20993. 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electronic access to the draft guidance document.
    Submit electronic comments on the draft guidance to http://www.regulations.gov.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: Alice Tu, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 22, Rm. 4325, Silver Spring, MD 20993-0002, 301-796-7586.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Over-the-Counter Pediatric Liquid Drug Products Containing 
Acetaminophen.'' Acetaminophen is

[[Page 60855]]

marketed in many OTC drug products as a pain reliever and fever 
reducer. A majority of OTC acetaminophen products are currently 
marketed under the conditions stated in FDA's tentative final monograph 
for internal analgesic, antipyretic, and antirheumatic drug products 
for over-the-counter human use (the IAAA TFM).\1\ In addition to the 
drug labeling requirements described in section 502 of the Federal 
Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 352) and Title 
21 of the Code of Federal Regulations (CFR), part 201, OTC 
acetaminophen products must also be labeled with liver injury warnings 
and other required information under Sec.  201.326 (21 CFR 201.326). 
The Agency allows acetaminophen to be marketed without approval of a 
new drug application (see generally section 505 of the FD&C Act (21 
U.S.C. 355) and 21 CFR part 314), in accordance with the IAAA TFM, and 
when the required acetaminophen-related warnings and other labeling 
requirements in Sec.  201.326 are met. However, OTC pediatric liquid 
drug products containing acetaminophen have been associated with 
overdoses due to medication errors that resulted in serious adverse 
events, including severe liver damage and death. In particular, there 
have been many reports of overdose attributed to confusion between 
concentrated acetaminophen drops (80 milligrams (mg)/0.8 milliliters 
(mL) and 80 mg/mL) and acetaminophen oral liquid (160 mg/5 mL).
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    \1\ ``Internal Analgesic, Antipyretic, and Antirheumatic Drug 
Products for Over-the-Counter Human Use; Tentative Final 
Monograph,'' 53 FR 46204 (November 16, 1988). Available at http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Over-the-CounterOTCDrugs/StatusofOTCRulemakings/UCM078460.pdf.
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    This draft guidance document is part of FDA's ongoing initiative to 
reduce the risk of acetaminophen-related liver injury associated with 
all OTC and prescription acetaminophen-containing products. As part of 
that initiative, in June 2009, three FDA committees, the Drug Safety 
and Risk Management Advisory Committee, the Nonprescription Drugs 
Advisory Committee, and the Anesthetic and Life Support Drugs Advisory 
Committee, met jointly to consider a range of risk reduction measures. 
Among other measures, the Advisory Committees recommended moving to a 
single, standardized acetaminophen concentration for OTC pediatric 
liquid drug products because the availability of multiple 
concentrations causes confusion and errors among both consumers and 
health care professionals. In May 2011, FDA convened a joint meeting of 
the Nonprescription Drugs Advisory Committee and the Pediatric Advisory 
Committee to discuss the use of acetaminophen in children. Shortly 
before the meeting, the Consumer Healthcare Products Association (CHPA) 
voluntarily proposed to phase out all of the existing concentrated drop 
formulations of the OTC, single-ingredient, oral, liquid acetaminophen 
drug products for pediatric use and market only the 160 mg/5 mL. At the 
Advisory Committee meeting, FDA took note of CHPA's voluntary 
transition to a single concentration of pediatric liquid acetaminophen. 
Among other recommendations, the Advisory Committees recommended the 
use of a flow restrictor or another feature designed to prevent 
excessive dosing, use of a safety dosing syringe to reduce accidental 
ingestion by children, and marking dosage delivery devices in 
milliliters only.\2\
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    \2\ Summary Minutes of the Joint Meeting of the Nonprescription 
Drugs Advisory Committee and the Pediatric Advisory Committee, held 
May 17-18, 2011, are available at http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/NonprescriptionDrugsAdvisoryCommittee/UCM264147.pdf.
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    In response to CHPA's voluntary transition to a single 
concentration of OTC liquid acetaminophen products, FDA published a 
Drug Safety Communication on December 22, 2011, to inform the public of 
the 160 mg/5 mL concentration now marketed for children ages 2 to 3 
years and to recommend that end users of the product read the Drug 
Facts label to identify the concentration of the liquid acetaminophen, 
dosage, and directions for use.
    FDA is issuing this guidance to address ongoing concerns about the 
potential for acetaminophen overdose associated with these products and 
to promote their safe use.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance 
represents the Agency's current thinking on addressing safety achieved 
through drug product design and labeling to minimize medication errors. 
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. 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.

III. Paperwork Reduction Act of 1995

    This draft guidance includes information collection provisions that 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3520). 
The collection of information referenced in this draft guidance that 
pertain to the format and content requirements for OTC drug product 
labeling (Sec.  201.66) have been approved under OMB control number 
0910-0340. The labeling requirements in Sec.  201.326 are not subject 
to review by the Office of Management and Budget because they do not 
constitute a ``collection of information'' under the PRA. 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)). In accordance with the 
PRA, prior to publication of any final guidance document, FDA intends 
to solicit public comment and obtain OMB approval for any information 
collections recommended in this guidance that are new or that would 
represent material modifications to those previously approved 
collections of information found in FDA regulations or guidances.

IV. Electronic Access

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

    Dated: October 1, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-23973 Filed 10-7-14; 8:45 am]
BILLING CODE 4164-01-P


