[Federal Register Volume 83, Number 93 (Monday, May 14, 2018)]
[Proposed Rules]
[Pages 22224-22225]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-10194]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 201 and 343

[Docket No. FDA-1977-N-0025]


Partial Withdrawal of Proposed Amendment to the Tentative Final 
Monograph for Internal Analgesic, Antipyretic, and Antirheumatic Drug 
Products for Over-the-Counter Use

AGENCY: Food and Drug Administration, HHS.

ACTION: Notification of partial withdrawal.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is 
announcing a partial withdrawal of a proposed rule published in the 
Federal Register of August 21, 2002 (2002 proposed rule). The proposed 
rule, if finalized, would have amended FDA's tentative final monograph 
(TFM) for over-the-counter (OTC) internal analgesic, antipyretic, and 
antirheumatic (IAAA) drug products to include ibuprofen as a generally 
recognized as safe and effective (GRASE) analgesic/antipyretic active 
ingredient for OTC use. FDA is withdrawing this proposed rule due to 
changes in our understanding of ibuprofen since FDA issued the proposed 
rule. FDA is not withdrawing those portions of the 2002 proposed rule 
to amend its regulations to include consistent pregnancy and allergy 
warnings for OTC IAAA drug products containing nonsteroidal anti-
inflammatory active ingredients.

DATES: As of May 14, 2018, FDA withdraws the proposed additions to 
Sec. Sec.  343.3 and 343.10, and proposed revisions to Sec. Sec.  
343.20 and 343.50 published on August 21, 2002 (67 FR 54139).

ADDRESSES: For access to the docket to read background documents or 
comments received, go to https://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 Dockets 
Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Kevin Lorick, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 5413, Silver Spring, MD 20993-0002, 301-
796-6696, [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of November 16, 1988 (53 FR 46204), FDA 
published a proposed rule in the form of a TFM that proposed conditions 
under which OTC IAAA drug products would be generally recognized as 
safe and effective and not misbranded. On August 21, 2002 (67 FR 
54139), FDA published a proposed rule that would have amended that TFM 
to include ibuprofen as a proposed GRASE analgesic/antipyretic active 
ingredient for OTC use. The 2002 proposed rule, if finalized, would 
have allowed manufacturers to market ibuprofen drug products for OTC 
use without submission of a new drug application (NDA), if all 
conditions of the monograph and other requirements were satisfied. At 
that time, ibuprofen drug products were marketed OTC under NDAs or 
abbreviated new drug applications (ANDAs) approved by FDA. This is 
still the case today--all ibuprofen drug products in the OTC 
marketplace are covered by NDAs or ANDAs. FDA is not aware of any 
ibuprofen drug products marketed under the TFM.
    In the same 2002 proposed rule, the Agency proposed to update FDA 
regulations in 21 CFR part 201 to include consistent pregnancy and 
allergy warnings for OTC IAAA drug products containing nonsteroidal 
anti-inflammatory active ingredients. This proposal, if finalized, 
would update pregnancy, allergy, and asthma statements required in the 
labeling of certain IAAA products. FDA is not

[[Page 22225]]

withdrawing that part of the proposed rule.
    On September 20, 2002, FDA held a meeting of the Nonprescription 
Drugs Advisory Committee to discuss safety issues related to the use of 
aspirin and other OTC nonsteroidal anti-inflammatory drugs (NSAIDs), 
including ibuprofen.\1\ Safety issues discussed included stomach 
bleeding. As a result of this meeting and subsequent FDA review of the 
data and additional comments submitted to the public docket (see Docket 
No. FDA-1977-N-0025), all OTC ibuprofen products marketed under NDAs 
and ANDAs bear warnings about gastrointestinal bleeding. Warnings state 
that the risk of bleeding is higher in persons who are age 60 or older, 
have stomach ulcers or bleeding problems, take a blood thinning 
(anticoagulant) or steroid drug, take other drugs containing 
prescription or nonprescription nonsteroidal anti-inflammatory drugs 
(NSAIDs), have three or more alcoholic drinks every day, or who take 
more or for a longer time than directed. These requirements are 
codified under 21 CFR 201.326(a)(2).
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    \1\ https://www.fda.gov/ohrms/dockets/ac/cder02.htm#NonprescriptionDrugs.
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    On February 10 and 11, 2014, FDA held a joint meeting of the 
Arthritis Advisory Committee and the Drug Safety and Risk Management 
Advisory Committee to discuss cardiovascular safety issues related to 
the use of NSAIDS, including ibuprofen.\2\ Safety issues included 
increased risk of heart attack and stroke that may be worsened with 
using too much NSAID or using NSAIDs for longer than recommended. Thus, 
FDA sent letters on August 18, 2016, to all manufacturers of ibuprofen 
requesting supplements to their applications to update labels with this 
new safety information. All OTC ibuprofen products now include label 
warnings against increased risk of heart attack and stroke with the use 
of NSAIDs other than aspirin.
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    \2\ https://wayback.archive-it.org/7993/20170404145443/https://www.fda.gov/AdvisoryCommittees/Calendar/ucm380871.htm.
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    To help ensure the continued utility of the consumer labeling as it 
relates to the safety of nonprescription ibuprofen drug products, FDA 
carefully monitors adverse event reporting.
    The safety issues that have arisen subsequent to the 2002 proposed 
rule have caused the Agency to question whether ibuprofen can be 
``generally recognized as safe and effective'' for use as an active 
ingredient in OTC IAAA drug products. For this reason, the Agency is 
withdrawing the 2002 proposed amendments to 21 CFR part 343. Our 
withdrawal of the 2002 proposed amendment to the IAAA TFM has no effect 
on the continued approval and marketing of the NDA and ANDA OTC 
ibuprofen drug products. As noted above, FDA has addressed the safety 
issues associated with ibuprofen through the NDA and ANDA safety 
framework, which is different from the safety framework for drugs 
marketed under the OTC monograph framework.
    FDA is not withdrawing those portions of the 2002 proposed rule to 
amend its regulations to include consistent pregnancy and allergy 
warnings for OTC IAAA drug products containing nonsteroidal anti-
inflammatory active ingredients.

II. Partial Withdrawal of the Proposed Rule

    For the reasons described in this document, FDA is withdrawing 
portions of the 2002 proposed rule, which would have amended the OTC 
IAAA TFM.

    Dated: May 8, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-10194 Filed 5-11-18; 8:45 am]
BILLING CODE 4164-01-P


