80 FR 71810 - 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
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 80, Issue 221 (November 17, 2015)
Food and Drug Administration
Federal Register Volume 80, Issue 221 (November 17, 2015)
| Page Range | 71810-71811 | |
| FR Document | 2015-29281 |
[Federal Register Volume 80, Number 221 (Tuesday, November 17, 2015)] [Notices] [Pages 71810-71811] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2015-29281] [[Page 71810]] ----------------------------------------------------------------------- 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. ----------------------------------------------------------------------- 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- [[Page 71811]] 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
![71810 Federal Register / Vol. 80, No. 221 / Tuesday, November 17, 2015 / Notices
DEPARTMENT OF HEALTH AND • If you want to submit a comment accordance with 21 CFR 10.20 and other
HUMAN SERVICES with confidential information that you applicable disclosure law. For more
do not wish to be made available to the information about FDA’s posting of
Food and Drug Administration public, submit the comment as a comments to public dockets, see 80 FR
[Docket No. FDA–2012–D–0529] written/paper submission and in the 56469, September 18, 2015, or access
manner detailed (see ‘‘Written/Paper the information at: http://www.fda.gov/
Organ-Specific Warnings: Internal Submissions’’ and ‘‘Instructions’’). regulatoryinformation/dockets/
Analgesic, Antipyretic, and Written/Paper Submissions default.htm.
Antirheumatic Drug Products for Over- Docket: For access to the docket to
the-Counter Human Use—Labeling for Submit written/paper submissions as read background documents or the
Products That Contain follows: electronic and written/paper comments
Acetaminophen; Guidance for • Mail/Hand delivery/Courier (for
received, go to http://
Industry; Availability written/paper submissions): Division of
www.regulations.gov and insert the
Dockets Management (HFA–305), Food
AGENCY: Food and Drug Administration, and Drug Administration, 5630 Fishers docket number, found in brackets in the
HHS. Lane, rm. 1061, Rockville, MD 20852. heading of this document, into the
• For written/paper comments ‘‘Search’’ box and follow the prompts
ACTION: Notice of availability.
submitted to the Division of Dockets and/or go to the Division of Dockets
SUMMARY: The Food and Drug Management, FDA will post your Management, 5630 Fishers Lane, rm.
Administration (FDA) is announcing the comment, as well as any attachments, 1061, Rockville, MD 20852.
availability of a guidance for industry except for information submitted, Submit written requests for single
entitled ‘‘Organ-Specific Warnings: marked and identified, as confidential, copies of this guidance to the Division
Internal Analgesic, Antipyretic, and if submitted as detailed in of Drug Information, Center for Drug
Antirheumatic Drug Products for Over- ‘‘Instructions.’’ Evaluation and Research, Food and
the-Counter Human Use—Labeling for Instructions: All submissions received Drug Administration, 10001 New
Products That Contain must include the Docket No. FDA– Hampshire Ave., Hillandale Building,
Acetaminophen.’’ The guidance is 2012–D–0529 for ‘‘Organ-Specific 4th Floor, Silver Spring, MD 20993–
intended to inform manufacturers of Warnings: Internal Analgesic, 0002. Send one self-addressed adhesive
certain nonprescription (also referred to Antipyretic, and Antirheumatic Drug label to assist that office in processing
as over-the-counter or OTC) internal Products for Over-the-Counter Human your requests. See the SUPPLEMENTARY
analgesic, antipyretic, and Use—Labeling for Products That INFORMATION section for electronic
antirheumatic (IAAA) drug products Contain Acetaminophen Guidance for access to the guidance document.
that contain acetaminophen of the Industry.’’ Received comments will be FOR FURTHER INFORMATION CONTACT:
circumstances for which FDA does not placed in the docket and, except for
Emily Baker, Office of Unapproved
intend to object to the inclusion of a those submitted as ‘‘Confidential
Drugs and Labeling Compliance, Center
liver warning that differs from that Submissions,’’ publicly viewable at
for Drug Evaluation and Research, Food
required under FDA regulations, http://www.regulations.gov or at the
and Drug Administration, 10903 New
provided the warning appears as Division of Dockets Management
Hampshire Ave., Silver Spring, MD
described in the guidance. between 9 a.m. and 4 p.m., Monday
20993–0002, 301–796–7524,
DATES: Submit either electronic or through Friday.
Emily.Baker@fda.hhs.gov.
written comments on Agency guidances • Confidential Submissions—To
at any time. submit a comment with confidential SUPPLEMENTARY INFORMATION:
ADDRESSES: You may submit comments information that you do not wish to be I. Background
as follows: made publicly available, submit your
comments only as a written/paper FDA is announcing the availability of
Electronic Submissions submission. You should submit two a guidance for industry entitled ‘‘Organ-
Submit electronic comments in the copies total. One copy will include the Specific Warnings: Internal Analgesic,
following way: information you claim to be confidential Antipyretic, and Antirheumatic Drug
• Federal eRulemaking Portal: http:// with a heading or cover note that states Products for Over-the-Counter Human
www.regulations.gov. Follow the ‘‘THIS DOCUMENT CONTAINS Use—Labeling for Products That
instructions for submitting comments. CONFIDENTIAL INFORMATION.’’ The Contain Acetaminophen.’’ In the
Comments submitted electronically, Agency will review this copy, including Federal Register of December 26, 2006
including attachments, to http:// the claimed confidential information, in (71 FR 77314), FDA published a
www.regulations.gov will be posted to its consideration of comments. The proposed rule on organ-specific
the docket unchanged. Because your second copy, which will have the warnings and related labeling for OTC
comment will be made public, you are claimed confidential information IAAA drug products. In the Federal
solely responsible for ensuring that your redacted/blacked out, will be available Register of April 29, 2009 (74 FR
comment does not include any for public viewing and posted on 19385), FDA published the final rule
confidential information that you or a http://www.regulations.gov. Submit (2009 final rule). In the Federal Register
third party may not wish to be posted, both copies to the Division of Dockets of November 25, 2009 (74 FR 61512),
such as medical information, your or Management. If you do not wish your FDA published a technical amendment
mstockstill on DSK4VPTVN1PROD with NOTICES
anyone else’s Social Security number, or name and contact information to be to clarify several provisions in response
confidential business information, such made publicly available, you can to industry feedback. The 2009 final
as a manufacturing process. Please note provide this information on the cover rule, as amended, changed some of the
that if you include your name, contact sheet and not in the body of your labeling requirements for OTC IAAA
information, or other information that comments and you must identify this drug products to inform consumers
identifies you in the body of your information as ‘‘confidential.’’ Any about the risk of liver injury when using
comments, that information will be information marked as ‘‘confidential’’ acetaminophen and the risk of stomach
posted on http://www.regulations.gov. will not be disclosed except in bleeding when using nonsteroidal anti-
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![Federal Register / Vol. 80, No. 221 / Tuesday, November 17, 2015 / Notices 71811
inflammatory drugs. It went into effect the regulation. To address this potential DEPARTMENT OF HEALTH AND
April 29, 2010. confusion, the Agency does not intend HUMAN SERVICES
Under that rule, the labeling for OTC to object to the inclusion of a liver
IAAA products that contain warning that differs from that required Food and Drug Administration
acetaminophen and are labeled for under § 201.326(a)(1)(iii)(A) and [Docket No. FDA–2014–N–0229]
adults only must include the liver § 201.326(a)(1)(v)(A), provided the
warning described below. Similarly, the warning appears as described in the Issuance of Priority Review Voucher;
labeling for OTC IAAA products that guidance. Rare Pediatric Disease Product
contain acetaminophen and are labeled
In the Federal Register of July 5, 2012 AGENCY: Food and Drug Administration,
for adults and children under 12 year of
(77 FR 39710), FDA published a draft HHS.
age must include a similar liver warning
guidance entitled ‘‘Organ-Specific ACTION: Notice.
described below.
Adults Only (§ 201.326(a)(1)(iii)(A) Warnings: Internal Analgesic,
(21 CFR 201.326(a)(1)(iii)(A))): Antipyretic, and Antirheumatic Drug SUMMARY: The Food and Drug
Products for Over-the-Counter Human Administration (FDA) is announcing the
Liver warning: This product contains Use—Labeling for Products That issuance of a priority review voucher to
acetaminophen. Severe liver damage may
Contain Acetaminophen.’’ The July the sponsor of a rare pediatric disease
occur if you take • more than [insert
maximum number of daily dosage units] in 2012 draft guidance gave interested product application. The Federal Food,
24 hours, which is the maximum daily persons an opportunity to submit Drug, and Cosmetic Act (the FD&C Act),
amount [optional: ‘‘for this product’’] • with comments through September 4, 2012. as amended by the Food and Drug
other drugs containing acetaminophen • 3 or We have made changes to the guidance Administration Safety and Innovation
more alcoholic drinks every day while using in response to comments received and Act (FDASIA), authorizes FDA to award
this product. have clarified the information in section priority review vouchers to sponsors of
Adults and children under 12 years of III of the draft guidance. rare pediatric disease product
age (§ 201.326(a)(1)(v)(A) (21 CFR This guidance is being issued applications that meet certain criteria.
201.326(a)(1)(v)(A))): consistent with FDA’s good guidance FDA has determined that STRENSIQ
Liver warning: This product contains (asfotase alfa), manufactured by Alexion
practices regulation (21 CFR 10.115).
acetaminophen. Severe liver damage may Pharmaceuticals, Inc., meets the criteria
The guidance represents the current
occur if • adult takes more than [insert thinking of FDA on Organ-Specific
for a priority review voucher.
maximum number of daily dosage units] in FOR FURTHER INFORMATION CONTACT:
24 hours, which is the maximum daily Warnings: Internal Analgesic,
Antipyretic, and Antirheumatic Drug Larry Bauer, Rare Diseases Program,
amount [optional: ‘‘for this product’’] • child Center for Drug Evaluation and
takes more than 5 doses in 24 hours • taken Products for Over-the-Counter Human
with other drugs containing acetaminophen Use—Labeling for Products That Research, Food and Drug
• adult has 3 or more alcoholic drinks every Contain Acetaminophen. It does not Administration, 10903 New Hampshire
day while using this product. establish any rights for any person and Ave., Bldg. 22, Rm. 6408, Silver Spring,
Although the currently proposed is not binding on FDA or the public. MD 20993–0002, 301–796–4842, FAX:
maximum daily dose of acetaminophen 301–796–9858, email: larry.bauer@
You can use an alternative approach if
is 4,000 milligrams (mg), some OTC fda.hhs.gov.
it satisfies the requirements of the
IAAA products that contain applicable statutes and regulations. SUPPLEMENTARY INFORMATION: FDA is
acetaminophen have directions for use announcing the issuance of a priority
that provide a maximum daily dose of II. Paperwork Reduction Act of 1965 review voucher to the sponsor of a rare
acetaminophen for that product that is The recommendations in this pediatric disease product application.
less than 4,000 mg. For example, for guidance are not subject to review by Under section 529 of the FD&C Act (21
some OTC IAAA drug products that the Office of Management and Budget U.S.C. 360ff), which was added by
contain both acetaminophen and one or FDASIA, FDA will award priority
because they do not constitute a
more other active ingredients, the review vouchers to sponsors of rare
‘‘collection of information’’ under the
maximum number of daily dosage units pediatric disease product applications
Paperwork Reduction Act of 1995 (44
might be limited by an active ingredient that meet certain criteria. FDA has
U.S.C. 3501 et seq.). Rather, the labeling
other than acetaminophen, which could determined that STRENSIQ (asfotase
statements are a ‘‘public disclosure of
result in a maximum daily dose of alfa), manufactured by Alexion
acetaminophen that is less than 4,000 information originally supplied by the Pharmaceuticals, Inc., meets the criteria
mg for that product. The optional Federal government to the recipient for for a priority review voucher. Asfotase
statement, ‘‘for this product,’’ in the first the purpose of disclosure to the public’’ alfa is a long-term enzyme replacement
bullet of the liver warning is intended (5 CFR 1320.3(c)(2)). therapy for patients with infantile- and
to address these situations by clarifying III. Electronic Access juvenile-onset hypophosphatasia (HPP).
that the maximum number of daily HPP is a rare genetic disorder that
dosage units for a product might not Persons with access to the Internet affects the development of bones and
reflect the maximum daily dose of may obtain the document at either teeth.
acetaminophen. http://www.fda.gov/Drugs/Guidance For further information about the Rare
However, the Agency understands ComplianceRegulatoryInformation/ Pediatric Disease Priority Review
mstockstill on DSK4VPTVN1PROD with NOTICES
that in certain circumstances, despite Guidances/default.htm or http:// Voucher Program and for a link to the
this optional statement, the wording of www.regulations.gov. full text of section 529 of the FD&C Act,
the first bullet in the warnings shown Dated: November 12, 2015. go to http://www.fda.gov/ForIndustry/
above might be interpreted as indicating DevelopingProductsforRareDiseases
Leslie Kux,
that severe liver damage is associated Conditions/RarePediatricDiseasePriority
with a total daily dose of Associate Commissioner for Policy. VoucherProgram/default.htm.
acetaminophen that is less than 4,000 [FR Doc. 2015–29281 Filed 11–16–15; 8:45 am] For further information about
mg. This suggestion is not the intent of BILLING CODE 4164–01–P STRENSIQ (asfotase alfa), go to the
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Document Created: 2015-12-14 14:00:03
Document Modified: 2015-12-14 14:00:03
| 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 of availability. | |
| Dates | Submit either electronic or written comments on Agency guidances at any time. | |
| 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] | |
| FR Citation | 80 FR 71810 |
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