80 FR 46588 - Over-the-Counter Pediatric Oral Liquid Drug Products Containing Acetaminophen; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 80, Issue 150 (August 5, 2015)

Page Range		46588-46589
FR Document		2015-19178

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.

Federal Register, Volume 80 Issue 150 (Wednesday, August 5, 2015)

[Federal Register Volume 80, Number 150 (Wednesday, August 5, 2015)]
[Notices]
[Pages 46588-46589]
From the Federal Register Online [www.thefederalregister.org]
[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

46588 Federal Register / Vol. 80, No. 150 / Wednesday, August 5, 2015 / Notices

considered as the guidance was DEPARTMENT OF HEALTH AND SUPPLEMENTARY INFORMATION:
finalized. The guidance announced in HUMAN SERVICES I. Background
this notice finalizes the draft guidance
dated June 2014. Food and Drug Administration FDA is announcing the availability of
a guidance for industry entitled ‘‘Over-
II. Significance of Guidance [Docket No. FDA–2014–D–1473]
the-Counter Pediatric Oral Liquid Drug
Over-the-Counter Pediatric Oral Liquid Products Containing Acetaminophen.’’
This level 1 guidance is being issued Acetaminophen is marketed in many
consistent with FDA’s good guidance Drug Products Containing
Acetaminophen; Guidance for OTC drug products as a pain reliever
practices regulation (21 CFR 10.115). and fever reducer. Most OTC
The guidance represents the current Industry; Availability
acetaminophen products are marketed
thinking of the Food and Drug AGENCY: Food and Drug Administration, under FDA’s ongoing rulemaking to
Administration (FDA or Agency) on the HHS. establish a final monograph for OTC
use of nanomaterials in food for ACTION: Notice. internal analgesic, antipyretic, and
animals. It does not establish any rights antirheumatic (IAAA) drug products.
for any person and is not binding on SUMMARY: The Food and Drug These products must conform to the
FDA or the public. You can use an Administration (FDA or the Agency) is conditions described in FDA’s Tentative
alternative approach if it satisfies the announcing the availability of a Final Monograph for Internal Analgesic,
requirements of the applicable statutes guidance for industry entitled ‘‘Over- Antipyretic, and Antirheumatic Drug
and regulations. the-Counter Pediatric Oral Liquid Drug Products for Over-the-Counter (OTC)
Products Containing Acetaminophen.’’ Human Use (the IAAA TFM) 1 and
III. Paperwork Reduction Act of 1995 The guidance is intended to help drug FDA’s general regulations for OTC drug
manufacturers, packagers, and labelers marketing (21 CFR 330.1) and labeling
This guidance refers to previously minimize the risk to consumers of (21 CFR 330.10 and part 201). They also
approved collections of information acetaminophen-related liver damage must be labeled with acetaminophen-
found in FDA regulations. These associated with the use of related warnings and other information
collections of information are subject to nonprescription, also known as over- as specified in 21 CFR 201.326.
review by the Office of Management and the-counter or OTC, pediatric oral liquid However, OTC pediatric oral liquid drug
Budget (OMB) under the Paperwork acetaminophen drug products. This products containing acetaminophen
Reduction Act of 1995 (44 U.S.C. 3501– guidance provides recommendations have been associated with overdoses
3520). The collections of information in regarding acetaminophen concentration, due to medication errors that resulted in
21 CFR 571.1 and 21 CFR 571.6 have container labels, carton labeling, and serious adverse events, including severe
been approved under 0910–0546. packaging of such products, as well as liver damage and death. In particular,
for any associated delivery devices. there have been reports of overdose
IV. Comments FDA’s recommendations are designed to attributed to confusion between
Interested persons may submit either encourage safer use of these products by concentrated acetaminophen drops (80
electronic comments regarding this minimizing the potential for milligrams (mg)/0.8 milliliters (mL) and
document to http://www.regulations.gov acetaminophen overdosing due to 80 mg/mL) and acetaminophen oral
or written comments to the Division of medication errors or accidental liquid (160 mg/5 mL).
ingestion. This guidance document is part of
Dockets Management (see ADDRESSES). It
is only necessary to send one set of DATES: Submit either electronic or FDA’s ongoing initiative to reduce the
written comments on Agency guidances risk of acetaminophen-related liver
comments. Identify comments with the
at any time. injury associated with all OTC and
docket number found in brackets in the
ADDRESSES: Submit written requests for
prescription acetaminophen-containing
heading of this document. Received
single copies of the guidance to the products. As part of that initiative, in
comments may be seen in the Division June 2009, three FDA committees, the
of Dockets Management between 9 a.m. Division of Drug Information, Center for
Drug Evaluation and Research, Food Drug Safety and Risk Management
and 4 p.m., Monday through Friday, and Advisory Committee, the
will be posted to the docket at http:// and Drug Administration, 10001 New
Hampshire Ave., Hillandale Building, Nonprescription Drugs Advisory
www.regulations.gov. Committee, and the Anesthetic and Life
4th Floor, Silver Spring, MD 20993–
V. Electronic Access 0002. Send one self-addressed adhesive Support Drugs Advisory Committee,
label to assist that office in processing met jointly to consider a range of risk
Persons with access to the Internet your requests. See the SUPPLEMENTARY reduction measures. Among other
may obtain the guidance at either INFORMATION section for electronic
measures, these Advisory Committees
http://www.fda.gov/AnimalVeterinary/ access to the guidance document. recommended moving to a single,
GuidanceComplianceEnforcement/ Submit electronic comments on the standardized acetaminophen
GuidanceforIndustry/default.htm or guidance to http://www.regulations.gov. concentration for OTC pediatric oral
http://www.regulations.gov. Submit written comments to the liquid drug products because the
Division of Dockets Management (HFA– availability of multiple concentrations
Dated: July 30, 2015. causes confusion and errors among both
305), Food and Drug Administration,
asabaliauskas on DSK5VPTVN1PROD with NOTICES

Leslie Kux, consumers and health care
5630 Fishers Lane, Rm. 1061, Rockville,
Associate Commissioner for Policy.
MD 20852. 1 ‘‘Internal Analgesic, Antipyretic, and
[FR Doc. 2015–19179 Filed 8–4–15; 8:45 am]
FOR FURTHER INFORMATION CONTACT: Antirheumatic Drug Products for Over-the-Counter
BILLING CODE 4164–01–P Alice Tu, Center for Drug Evaluation Human Use; Tentative Final Monograph,’’ 53 FR
and Research, Food and Drug 46204 (November 16, 1988). Available at http://
www.fda.gov/downloads/Drugs/Development
Administration, 10903 New Hampshire ApprovalProcess/DevelopmentResources/Over-the-
Ave., Bldg. 22, Rm. 4325, Silver Spring, CounterOTCDrugs/StatusofOTCRulemakings/
MD 20993–0002, 301–796–7586. UCM078460.pdf.

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Federal Register / Vol. 80, No. 150 / Wednesday, August 5, 2015 / Notices 46589

professionals. In May 2011, FDA III. Paperwork Reduction Act of 1995 Date: November 4, 2015.
convened a joint meeting of the Time: 8:30 a.m. to 4:00 p.m.
This guidance refers to a previously Agenda: Strategic Discussion of NCI’s
Nonprescription Drugs Advisory approved collection of information Clinical and Translational Research
Committee and the Pediatric Advisory found in FDA regulations. The Programs.
Committee to discuss the use of collection of information is subject to Place: National Institutes of Health,
acetaminophen in children. Shortly review by the Office of Management and Building 31, C-Wing, 6th Floor, Room 10, 31
before the meeting, the Consumer Budget (OMB) under the Paperwork Center Drive, Bethesda, MD 20892.
Healthcare Products Association Reduction Act of 1995 (PRA) (44 U.S.C. Contact Person: Sheila A. Prindiville, MD,
(CHPA) proposed to voluntarily phase MPH, Director, Coordinating Center for
3501–3520). The collection of
out all of the existing single-ingredient Clinical Trials, National Institutes of Health,
information referenced in this guidance National Cancer Institute, 9609 Medical
concentrated drop formulations of the that pertain to the format and content Center Drive, Room 6W136, Rockville, MD
OTC, pediatric, oral, liquid requirements for OTC drug product 20850, 240–276–6173, prindivs@
acetaminophen drug products and labeling (§ 201.66) have been approved mail.nih.gov.
market only the 160 mg/5 mL. At the under OMB control number 0910–0340. Any interested person may file written
Advisory Committee meeting, FDA took The labeling requirements in § 201.326 comments with the committee by forwarding
note of CHPA’s voluntary transition to are not subject to review by OMB the statement to the Contact Person listed on
a single concentration of pediatric oral this notice. The statement should include the
because they do not constitute a
liquid acetaminophen. name, address, telephone number and when
‘‘collection of information’’ under the applicable, the business or professional
In response to CHPA’s voluntary PRA. Rather, the labeling statements are
transition to a single concentration of affiliation of the interested person.
a ‘‘public disclosure of information In the interest of security, NIH has
OTC oral liquid acetaminophen originally supplied by the Federal instituted stringent procedures for entrance
products, FDA published a Drug Safety government to the recipient for the onto the NIH campus. All visitor vehicles,
Communication on December 22, 2011, purpose of disclosure to the public’’ (5 including taxicabs, hotel, and airport shuttles
to inform the public of the 160 mg/5 mL CFR 1320.3(c)(2)). will be inspected before being allowed on
concentration now marketed for campus. Visitors will be asked to show one
children ages 2 to 3 years and to IV. Electronic Access form of identification (for example, a
recommend that end users of the government-issued photo ID, driver’s license,
Persons with access to the Internet
product read the Drug Facts label to or passport) and to state the purpose of their
may obtain the document at either visit.
identify the concentration of the oral http://www.fda.gov/Drugs/Guidance Information is also available on the
liquid acetaminophen, dosage, and ComplianceRegulatoryInformation/ Institute’s/Center’s home page: http://
directions for use. Guidances/default.htm or http:// deainfo.nci.nih.gov/advisory/ctac/ctac.htm,
FDA issued the draft guidance on www.regulations.gov. where an agenda and any additional
October 8, 2014 (79 FR 60854), to information for the meeting will be posted
address ongoing concerns about the Dated: July 30, 2015.
when available.
potential for acetaminophen overdose Leslie Kux,
(Catalogue of Federal Domestic Assistance
associated with these products and to Associate Commissioner for Policy. Program Nos. 93.392, Cancer Construction;
encourage safer use. Comments on the [FR Doc. 2015–19178 Filed 8–4–15; 8:45 am] 93.393, Cancer Cause and Prevention
draft guidance were considered while BILLING CODE 4164–01–P Research; 93.394, Cancer Detection and
finalizing this guidance, which has been Diagnosis Research; 93.395, Cancer
revised and clarified in some respects. Treatment Research; 93.396, Cancer Biology
This guidance is being issued DEPARTMENT OF HEALTH AND Research; 93.397, Cancer Centers Support;
HUMAN SERVICES 93.398, Cancer Research Manpower; 93.399,
consistent with FDA’s good guidance Cancer Control, National Institutes of Health,
practices regulation (21 CFR 10.115). HHS)
The guidance represents the current National Institutes of Health
thinking of FDA on addressing safety Dated: July 31, 2015.
National Cancer Institute; Notice of David Clary,
achieved through drug product design Open Meeting
and labeling to minimize medication Program Analyst, Office of Federal Advisory
errors. It does not establish any rights Pursuant to section 10(a) of the Committee Policy.
for any person and is not binding on Federal Advisory Committee Act, as [FR Doc. 2015–19193 Filed 8–4–15; 8:45 am]
FDA or the public. You can use an amended (5 U.S.C. App.), notice is BILLING CODE 4140–01–P
alternative approach if it satisfies the hereby given of a meeting of the
requirements of the applicable statutes National Cancer Institute Clinical Trials
and regulations. and Translational Research Advisory DEPARTMENT OF HEALTH AND
Committee. HUMAN SERVICES
II. Comments The meeting will be open to the
Interested persons may submit either public, with attendance limited to space National Institutes of Health
electronic comments regarding this available. Individuals who plan to
Submission for OMB Review; 30 Day
document to http://www.regulations.gov attend and need special assistance, such
Comment Request; Post-Award
or written comments to the Division of as sign language interpretation or other
Reporting Requirements Including
Dockets Management (see ADDRESSES). It reasonable accommodations, should
Research Performance Progress
is only necessary to send one set of notify the Contact Person listed below
asabaliauskas on DSK5VPTVN1PROD with NOTICES

Report Collection (OD/OPERA)
comments. Identify comments with the in advance of the meeting. The meeting
docket number found in brackets in the will also be videocast and can be SUMMARY: Under the provisions of
heading of this document. Received accessed from the NIH Videocasting and section 3507(a)(1)(D) of the Paperwork
comments may be seen in the Division Podcasting Web site (http://videocast. Reduction Act of 1995, the National
of Dockets Management between 9 a.m. nih.gov/). Institutes of Health (NIH) has submitted
and 4 p.m., Monday through Friday, and Name of Committee: National Cancer to the Office of Management and Budget
will be posted to the docket at http:// Institute Clinical Trials and Translational (OMB) a request for review and
www.regulations.gov. Research Advisory Committee. approval of the information collection

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Document Created: 2018-02-23 10:53:07
Document Modified: 2018-02-23 10:53:07

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice.
Dates		Submit either electronic or written comments on Agency guidances at any time.
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.
FR Citation		80 FR 46588

80 FR 46588 - Over-the-Counter Pediatric Oral Liquid Drug Products Containing Acetaminophen; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 80, Issue 150 (August 5, 2015)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration