
[Federal Register Volume 80, Number 150 (Wednesday, August 5, 2015)]
[Notices]
[Pages 46588-46589]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-19178]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


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

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is 
announcing the availability of a guidance for industry entitled ``Over-
the-Counter Pediatric Oral Liquid Drug Products Containing 
Acetaminophen.'' The 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 or OTC, pediatric oral 
liquid acetaminophen drug products. This guidance provides 
recommendations regarding acetaminophen concentration, container 
labels, carton labeling, and packaging of such products, as well as for 
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: Submit either electronic or written comments on Agency guidances 
at any time.

ADDRESSES: Submit written requests for single copies of the 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.
    Submit electronic comments on the 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 guidance for industry 
entitled ``Over-the-Counter Pediatric Oral Liquid Drug Products 
Containing Acetaminophen.'' Acetaminophen is marketed in many OTC drug 
products as a pain reliever and fever reducer. Most OTC acetaminophen 
products are marketed under FDA's ongoing rulemaking to establish a 
final monograph for OTC internal analgesic, antipyretic, and 
antirheumatic (IAAA) drug products. These products must conform to the 
conditions described in FDA's Tentative Final Monograph for Internal 
Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-
Counter (OTC) Human Use (the IAAA TFM) \1\ and FDA's general 
regulations for OTC drug marketing (21 CFR 330.1) and labeling (21 CFR 
330.10 and part 201). They also must be labeled with acetaminophen-
related warnings and other information as specified in 21 CFR 201.326. 
However, OTC pediatric oral 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 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 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, these Advisory Committees recommended moving to a 
single, standardized acetaminophen concentration for OTC pediatric oral 
liquid drug products because the availability of multiple 
concentrations causes confusion and errors among both consumers and 
health care

[[Page 46589]]

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) 
proposed to voluntarily phase out all of the existing single-ingredient 
concentrated drop formulations of the OTC, pediatric, oral, liquid 
acetaminophen drug products 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 oral liquid 
acetaminophen.
    In response to CHPA's voluntary transition to a single 
concentration of OTC oral 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 oral liquid 
acetaminophen, dosage, and directions for use.
    FDA issued the draft guidance on October 8, 2014 (79 FR 60854), to 
address ongoing concerns about the potential for acetaminophen overdose 
associated with these products and to encourage safer use. Comments on 
the draft guidance were considered while finalizing this guidance, 
which has been revised and clarified in some respects.
    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 addressing safety achieved through drug 
product design and labeling to minimize medication errors. 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. 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 guidance refers to a previously approved collection of 
information found in FDA regulations. The collection of information is 
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 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 
OMB 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)).

IV. 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: July 30, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-19178 Filed 8-4-15; 8:45 am]
 BILLING CODE 4164-01-P


