[Federal Register Volume 86, Number 180 (Tuesday, September 21, 2021)]
[Notices]
[Pages 52474-52478]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-20393]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-N-0952]


Final Administrative Orders for Over-the-Counter Monographs; 
Availability

AGENCY: Food and Drug Administration, Health and Human Services (HHS).

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability on its website of certain final administrative orders 
(final orders), including for over-the-counter (OTC) drug monographs, 
that were deemed to be final orders by the Coronavirus Aid, Relief, and 
Economic Security Act (CARES Act), which added a new section to the 
Federal Food, Drug, and Cosmetic Act (FD&C Act). FDA is also announcing 
the process for making these final orders available. Finally, FDA is 
announcing its plan for withdrawing regulations that established final 
OTC drug monographs prior to the passage of the CARES act, and 
withdrawing or making technical changes to the procedures governing the 
OTC drug review.

DATES: The announcement of the availability on FDA's website of certain 
final orders as deemed by section 505G of the FD&C Act and other 
actions related to section 505G is published in the Federal Register on 
September 21, 2021.

ADDRESSES: You may view the final orders in the OTC Monographs@FDA 
portal at https://www.accessdata.fda.gov/scripts/cder/omuf/index.cfm.
     Instructions: For access to the final orders, go to 
https://www.accessdata.fda.gov/scripts/cder/omuf/index.cfm. Under the 
``Administrative Orders'' banner, click on the desired link under the 
``Order ID'' heading and follow the prompts.

FOR FURTHER INFORMATION CONTACT: Helen Lee, Center for Drug Evaluation 
and Research (HFD-600), Food and Drug Administration, 10903 New 
Hampshire Ave., Silver Spring, MD 20993-0002, 301-796-6848.

SUPPLEMENTARY INFORMATION:

I. Background

    On March 27, 2020, the CARES Act was signed into law. The CARES Act 
includes provisions that govern the way certain OTC drugs are regulated 
in the United States. In particular, the CARES Act added section 505G 
to the FD&C Act (21 U.S.C. 355g), which reforms and modernizes the OTC 
drug review process that was established in 1972. Under the OTC drug 
review, OTC drug monographs (also referred to as OTC monographs) for 
different therapeutic categories are established. OTC drugs are 
generally recognized as safe and effective (GRASE) if they meet the 
conditions of an OTC monograph, including the specified active 
ingredients, uses (indications), doses, routes of administration, 
labeling, and testing, along with other applicable requirements.

A. Regulatory Framework for OTC Monograph Drugs Prior to the Passage of 
the CARES Act

    Prior to passage of the CARES Act, OTC monographs were established, 
revised, and amended using the rulemaking process set out by the 
Administrative Procedure Act in 21 U.S.C. 553. Final OTC monographs 
(final monographs) were codified in regulations under title 21 of the 
CFR. The OTC monograph process was set forth in 21 CFR part 330 (part 
330). Prior to establishment of a final monograph, GRASE conditions for 
a therapeutic category were set forth in proposed rules as tentative 
final monographs. At the time of the passage of the CARES Act, certain 
OTC monographs were still at the proposed rulemaking stage, either in 
whole or in part.
    In the course of the OTC drug review, FDA also determined when 
there was not sufficient evidence to demonstrate certain conditions 
(e.g., active ingredients for specific uses) were GRASE. In such cases, 
FDA often expressly codified these determinations that certain 
conditions were not GRASE (see, e.g., Sec.  310.545 (21 CFR 310.545)). 
In addition, part 201, subpart G (21 CFR part 201, subpart G), includes 
specific labeling requirements for certain drugs, including OTC 
monograph drugs (see, e.g., Sec.  201.326, requiring warnings and other 
labeling for OTC drug products containing internal analgesic and 
antipyretic active ingredients).

B. Regulatory Framework for OTC Monograph Drugs Under the CARES Act

    The CARES Act added section 505G to the FD&C Act, which revised the 
framework for the regulation of OTC

[[Page 52475]]

monograph drugs.\1\ Under section 505G of the FD&C Act, the rulemaking 
process for establishing, revising, and amending OTC monographs was 
replaced with an administrative order process. In addition, among other 
things, section 505G of the FD&C Act provides a baseline status that, 
as of the date of enactment of the CARES Act, a drug that satisfies 
certain requirements described in section 505G(a)(1) or (2) is: (1) 
Deemed to be generally recognized as safe and effective under section 
201(p)(1) of the FD&C Act (21 U.S.C. 321(p)(1); (2) not a new drug 
under section 201(p) of the FD&C Act; and (3) not subject to section 
503(b)(1) of the FD&C Act (21 U.S.C. 353(b)(1)). To obtain this status, 
among other things, a drug either must be one that is in conformity 
with the requirements for nonprescription use of a final monograph 
issued under part 330 (except as provided in section 505G(a)(2) of the 
FD&C Act),\2\ as well as other requirements; \3\ or must be one that 
is: (1) Classified in category I for safety and effectiveness under a 
tentative final monograph that is the most recently applicable proposal 
or determination issued under part 330 and (2) in conformity with the 
proposed requirements for nonprescription use of such tentative final 
monograph and any applicable subsequent determination by FDA, as well 
as other requirements.\4\ Other applicable requirements in section 
505G(a)(1) of the FD&C Act include conditions or requirements under 
section 505G(b), (c), and (k) of the FD&C Act.
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    \1\ OTC drugs that are governed by the provisions of section 
505G of the FD&C Act are referred to as OTC monograph drugs.
    \2\ Section 505G(a)(2) of the FD&C Act provides specific 
requirements for sunscreen drugs in terms of conformity with a final 
monograph, for purposes of section 505G(a)(1)(A)(i) of the FD&C Act.
    \3\ Section 505G(a)(1)(A) of the FD&C Act.
    \4\ Section 505G(a)(1)(B) of the FD&C Act.
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    Complementary to the requirements for conformity to tentative final 
or final monographs described in section 505G(a)(1) and (2) of the FD&C 
Act, Congress provided that, under section 505G(b)(8) of the FD&C Act, 
a final monograph or tentative final monograph that establishes 
conditions of use for a drug described in section 505G(a)(1) or (2) of 
the FD&C Act and that represents the most recently issued version of 
the conditions of use, including as modified, in whole or in part, by 
any proposed or final rule, is deemed to be a final order. These deemed 
final orders provide the current OTC drug monograph conditions that are 
in effect for each therapeutic category addressed by them. Final orders 
may be amended, revoked, or otherwise modified in accordance with the 
procedures of section 505G of the FD&C Act. Under section 505G(b)(8)(C) 
of the FD&C Act, the deemed establishment of a final order is construed 
to include technical amendments necessary to ensure that the final 
order is appropriately harmonized, in terms of terminology or cross-
references, with the applicable provisions of the FD&C Act (and 
regulations) and any other final orders issued under section 505G.
    Congress also deemed certain regulations, as in effect on the day 
before the date of the enactment of the CARES Act (i.e., March 26, 
2020), to be final orders under section 505G(b) of the FD&C Act. In 
particular, section 505G(k)(2)(A) of the FD&C Act deemed the provisions 
of Sec.  310.545 to be a final order under section 505G(b). Also, 
section 505G(k)(2)(B) of the FD&C Act deemed regulations establishing 
requirements for specific nonprescription drugs marketed pursuant to 
section 505G (including such requirements in 21 CFR parts 201 and 250) 
to be final orders under section 505G(b), as they apply to drugs 
subject to section 505G(a)(1) through (4) or otherwise subject to an 
order under section 505G.
    In addition, section 505G(k)(3) of the FD&C Act provides that 
regulations establishing final monographs and the procedures governing 
the OTC drug review under part 330 and other relevant parts of title 21 
of the CFR, shall be withdrawn or revised to make technical changes to 
ensure conformity with appropriate terminology and cross-references. 
Section 505G(k)(3) of the FD&C Act also provides that any such 
withdrawal or technical changes shall be made without public notice and 
comment and shall be effective upon publication through notice in the 
Federal Register (or upon such date as specified in such notice).

II. Procedures for Posting Final Orders as Deemed by Section 505G of 
the FD&C Act

    The final orders as deemed by section 505G of the FD&C Act were 
made effective upon enactment of the CARES Act on March 27, 2020. By 
this notice, FDA is announcing the availability on its website of 
certain deemed final orders and providing the public information on the 
process for making available deemed final orders, including details on 
how the public can access and view the final orders. FDA is posting 
these final orders to provide the public a convenient resource to view 
OTC monographs and non-monograph conditions. The process for FDA 
issuing proposed, final, and interim final orders under section 505G(b) 
of the FD&C Act to add, modify, or remove OTC monograph conditions is 
generally described in section 505G(b) and is not addressed in this 
Notice. Additional information, including questions and answers on this 
process, can be found on FDA's OTC monograph web page at https://www.fda.gov/drugs/over-counter-otc-nonprescription-drugs/over-counter-otc-drug-review-otc-monograph-reform-cares-act, and further information 
will be provided when FDA issues its first proposed order.

A. Process for Making Available Final Orders as Deemed by Section 
505G(b)(8) of the FD&C Act

    FDA is announcing its process for making available final orders as 
deemed by section 505G(b)(8) of the FD&C Act. FDA reviewed all final 
monographs published in the CFR, beginning with 21 CFR part 331, and 
the rulemaking histories for each OTC monograph therapeutic category, 
to identify all relevant final monographs and tentative final 
monographs that established conditions of use for a drug described in 
section 505G(a)(1) of the FD&C Act and that represented the most 
recently issued version of the conditions of use, including as 
modified, in whole or in part, by any proposed or final rule. As noted 
above, the relevant requirements for sunscreen drugs subject to section 
505G of the FD&C Act, in terms of conformity with a final monograph for 
purposes of section 505G(a)(1)(A)(i), were set forth in section 
505G(a)(2) and consist of the requirements specified in 21 CFR part 
352, as published on May 21, 1999, except that the applicable 
requirements governing effectiveness and labeling are those specified 
in Sec.  201.327. Altogether, as indicated in table 1 below, FDA 
identified 32 final orders created by section 505G(b)(8) of the FD&C 
Act.
    As further discussed below, FDA also identified certain regulations 
that established requirements for specific nonprescription drugs 
marketed pursuant to section 505G of the FD&C Act and, therefore, were 
deemed final orders by section 505G(k)(2)(B), only as they apply to 
drugs subject to section 505G(a)(1) through (4) or otherwise subject to 
an order under section 505G (e.g., Sec.  201.326, which set forth 
certain labeling requirements regarding warnings for OTC drug products 
containing internal analgesic and antipyretic active ingredients). To 
the extent regulations that were deemed to be final orders by section 
505G(k)(2)(B) of the FD&C Act apply to OTC drugs addressed by a final 
order embodying an

[[Page 52476]]

OTC monograph, as deemed by section 505G(b)(8) of the FD&C Act, the 
relevant provisions may be incorporated into the final order(s) 
embodying the OTC monograph(s).
    FDA assigned OTC monograph numbers to the resulting deemed final 
orders (see table 1). Table 1 provides the corresponding OTC monograph 
number and title for each of these OTC monographs and identifies the 
CFR citation, if applicable. Additionally, an order ID will be assigned 
in sequential order upon posting of all orders, including the deemed 
final orders.
    Each OTC monograph embodied by a deemed final order is accompanied 
by a summary and a background section. In the background section, FDA 
describes the relevant proposed and final rules that constitute the 
deemed final order. Additionally, pursuant to section 505G(b)(8)(C) of 
the FD&C Act, OTC monographs embodied by deemed final orders include 
any technical amendments that are determined to be necessary to ensure 
that they are appropriately harmonized, in terms of terminology and 
cross-references, with applicable provisions of the FD&C Act, FDA 
regulations, and any other orders issued under section 505G. The 
background section generally describes any differences between the 
deemed final order and the proposed and final rules that constitute the 
order.
    Some OTC monographs incorporate by reference specified material, 
published by an entity other than the United States government (e.g., 
an ISO standard). This incorporated material is available for 
inspection at FDA. For further information about inspecting 
incorporated materials, see https://www.fda.gov/drugs/over-counter-otc-nonprescription-drugs/over-counter-otc-drug-review-otc-monograph-reform-cares-act. Copies of incorporated material may also be available 
from its publisher.

Table 1--OTC Monographs as Represented by Final Orders Deemed by Section
                       505G(b)(8) of the FD&C Act
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                        CFR citation in
 OTC monograph number      title 21            OTC monograph title
------------------------------------------------------------------------
M001.................  Part 331........  Antacid Products for OTC Human
                                          Use.
M002.................  Part 332........  Antiflatulent Products for OTC
                                          Human Use.
M003.................  N/A \1\.........  First Aid Antiseptic Drug
                                          products for OTC Human Use.
M004.................  Part 333,         First Aid Antibiotic Drug
                        subpart B.        Products for OTC Human Use.
M005.................  Part 333,         Topical Antifungal Drug
                        subpart C.        Products for OTC Human Use.
M006.................  Part 333,         Topical Acne Drug Products for
                        subpart D.        OTC Human Use.
M007.................  N/A\1\..........  Laxative Drug Products for OTC
                                          Human Use.
M008.................  Part 335........  Antidiarrheal Drug Products for
                                          OTC Human Use.
M009.................  Part 336........  Antiemetic Drug Products for
                                          OTC Human Use.
M010.................  Part 338........  Nighttime Sleep Aid Drug
                                          Products for OTC Human Use.
M011.................  Part 340........  Stimulant Drug Products for OTC
                                          Human Use.
M012.................  Part 341........  Cold, Cough, Allergy,
                                          Bronchodilator, and
                                          Antiasthmatic Drug Products
                                          for OTC Human Use.
M013.................  Part 343........  Internal Analgesic,
                                          Antipyretic, and Antirheumatic
                                          Drug Products for OTC Human
                                          Use.
M014.................  Part 344........  Topical Otic Drug Products for
                                          OTC Human Use.
M015.................  Part 346........  Anorectal Drug Product for OTC
                                          Human Use.
M016.................  Part 347........  Skin Protectant Drug Products
                                          for OTC Human Use.
M017.................  Part 348........  External Analgesic Drug Product
                                          for OTC Human Use.
M018.................  Part 349........  Ophthalmic Drug Products for
                                          OTC Human Use.
M019.................  Part 350........  Antiperspirant Drug Products
                                          for OTC Human Use.
M020.................  Part 352........  Sunscreen Drug Products for OTC
                                          Human Use.
M021.................  Part 355........  Anticaries Drug Products for
                                          OTC Human Use.
M022.................  N/A \1\.........  Oral Health Care Drug Products
                                          for OTC Human Use.
M023.................  N/A \1\.........  Poison Treatment Drug Products
                                          for OTC Human Use.
M024.................  Part 357,         Anthelminic Drug Products for
                        subpart B.        OTC Human Use.
M025.................  Part 357,         Cholecystokinetic Drug Products
                        subpart C.        for OTC Human Use.
M026.................  Part 357,         Deodorant Drug Products for
                        subpart I.        Internal Use for OTC Human
                                          Use.
M027.................  N/A \1\.........  Orally Administered Menstrual
                                          Drug Products for OTC Human
                                          Use.
M028.................  Part 358,         Wart Remover Drug Products for
                        subpart B.        OTC Human Use.
M029.................  Part 358,         Ingrown Toenail Relief Drug
                        subpart D.        Products for OTC Human Use.
M030.................  Part 358,         Corn and Callus Remover Drug
                        subpart F.        Products for OTC Human Use.
M031.................  Part 358,         Pediculicide Drug Products for
                        subpart G.        OTC Human Use.
M032.................  Part 358,         Drug Products for the Control
                        subpart H.        of Dandruff, Seborrheic
                                          Dermatitis, and Psoriasis for
                                          OTC Human Use.
------------------------------------------------------------------------
\1\ Not applicable as there is no relevant CFR citation (i.e., there
  were no final monographs at the time of enactment of the CARES Act).

B. Process for Making Available Final Orders as Deemed by Section 
505G(k)(2) of the FD&C Act

    Under section 505G(k)(2)(A) of the FD&C Act, the non-monograph 
conditions in Sec.  310.545 in effect on the day before the date of 
enactment of the CARES Act (i.e., March 26, 2020) were deemed to be a 
final order under section 505G(b). The provisions of Sec.  310.545 list 
active ingredients for which there is not sufficient data to establish 
general recognition of the safety and effectiveness for the specified 
use in OTC drug products. Before posting the deemed final order 
containing these provisions, FDA intends to remove the compliance dates 
found in the regulation because the dates are no longer relevant, since 
any current product would have been introduced or delivered for 
introduction into interstate commerce well after the compliance date. 
FDA also intends to rearrange the listed active ingredients within each 
provision regarding a particular therapeutic category so that they 
generally appear in alphabetical order. When posting this final order, 
FDA will assign a final order ID and OTC non-monograph conditions 
number.
    In addition, under section 505G(k)(2)(B) of the FD&C Act, 
regulations in effect on March 26, 2020, establishing requirements for 
specific

[[Page 52477]]

nonprescription drugs marketed pursuant to section 505G of the FD&C Act 
were deemed final orders under section 505G(b), only as they apply to 
drugs subject to section 505G(a)(1) through (4) of the FD&C Act or 
otherwise subject to a final order under section 505G. As discussed 
above, provisions from a regulation that was deemed to be a final order 
by section 505G(k)(2)(B) of the FD&C Act may be incorporated into a 
relevant final order embodying an OTC monograph under section 
505G(b)(8). A deemed final order under section 505G(k)(2)(B) of the 
FD&C Act may also be posted as a separate, standalone final order. In 
the latter case, FDA intends to issue an accompanying notice in the 
Federal Register announcing its availability on our website. 
Regulations deemed to be final orders by section 505G(k)(2)(B) of the 
FD&C Act will remain in the CFR to the extent they also apply to drugs 
that are not subject to section 505G(a)(1) through (4) or otherwise 
subject to an order under section 505G.

C. Availability of Final Orders Including Those Deemed by Section 505G 
of the FD&C Act

    FDA has established a new IT system with a web portal, OTC 
Monographs@FDA, which can be accessed through FDA's website. The portal 
will provide access to a repository of final orders under section 505G 
of the FD&C Act and is available at https://www.accessdata.fda.gov/scripts/cder/omuf/index.cfm. To access the final orders, go to the OTC 
Monographs@FDA portal at https://www.accessdata.fda.gov/scripts/cder/omuf/index.cfm. Under the ``Administrative Orders'' banner, click on 
the desired link under the ``Order ID'' heading and follow the prompts.
    For ease of reference, FDA also is posting in the OTC 
Monographs@FDA portal the individual OTC monographs embodied by final 
orders under section 505G(b) of the FD&C Act, without any sections that 
accompany the monograph, such as the background section. To access just 
the OTC monographs, under the ``OTC Monographs'' banner, click on the 
desired link under the ``OTC Monograph ID'' heading and follow the 
prompts.
    FDA will make available deemed final orders embodying OTC 
monographs in batches on a rolling basis until all 32 such orders, 
discussed above in section II.A (see also table 1), are available in 
the repository. FDA will also make available in the repository the 
final order that reflects the provisions of Sec.  310.545, as deemed by 
section 505G(k)(2)(A) of the FD&C Act, and final orders regarding 
requirements for specific nonprescription drugs, as deemed by section 
505G(k)(2)(B).
    FDA is announcing that the OTC Monographs@FDA portal currently 
includes an initial batch of four deemed final orders embodying OTC 
monographs (see table 2). The posting of the remainder of these 32 
deemed final orders, as well as the deemed final order under section 
505G(k)(2)(A) of the FD&C Act, will not be announced in the Federal 
Register but will be announced on FDA's OTC monograph web page, https://www.fda.gov/drugs/over-counter-otc-nonprescription-drugs/over-counter-otc-drug-review-otc-monograph-reform-cares-act. FDA plans to issue a 
notice of availability in the Federal Register when posting in the 
repository final orders deemed by section 505G(k)(2)(B) of the FD&C 
Act.

              Table 2--Initial Batch of Posted Final Orders Deemed by Section 505G of the FD&C Act
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                                                          CFR citation in
         Order ID              OTC monograph number          Title 21                OTC monograph title
----------------------------------------------------------------------------------------------------------------
OTC000001.................  M002.....................  Part 332............  Antiflatulent Products for OTC
                                                                              Human Use.
OTC000002.................  M010.....................  Part 338............  Nighttime Sleep-Aid Drug Products
                                                                              for OTC Human Use.
OTC000003.................  M014.....................  Part 344............  Topical Otic Drug Products for OTC
                                                                              Human Use.
OTC000004.................  M030.....................  Part 358, Subpart F.  Corn and Callus Remover Drug
                                                                              Products for OTC Human Use.
----------------------------------------------------------------------------------------------------------------

    FDA encourages the public to frequently view our website at https://www.fda.gov/drugs/over-counter-otc-nonprescription-drugs/over-counter-otc-drug-review-otc-monograph-reform-cares-act and the OTC 
Monographs@FDA portal for the most up-to-date information about the 
status of posted final orders as deemed by section 505G of the FD&C 
Act. Questions regarding these final orders can be submitted to FDA at 
[email protected].
    In the future, the repository will also include proposed orders, 
final orders, and interim final orders to add, amend, or remove OTC 
monograph conditions that are issued by FDA either on its own 
initiative or pursuant to an OTC monograph order request under section 
505G(b)(5) of the FD&C Act. Information on the process for FDA issuing 
proposed, final, and interim final orders is provided in section 
505G(b) of the FD&C Act. Additional information, including questions 
and answers on this process, can be found on FDA's OTC monograph web 
page (https://www.fda.gov/drugs/over-counter-otc-nonprescription-drugs/over-counter-otc-drug-review-otc-monograph-reform-cares-act), which 
will continue to be updated as FDA issues new orders.

III. Procedures for Withdrawing Regulations for Final Monographs and 
the Procedures Governing the OTC Drug Review, and Withdrawing and 
Making Technical Changes to Regulations in Part 330 and Other Relevant 
Parts of Title 21 of the CFR

    Under section 505G(k)(3) of the FD&C Act, regulations establishing 
final monographs and the procedures governing the OTC drug review under 
part 330 and other relevant parts of title 21 of the CFR (as in effect 
on March 26, 2020) shall be withdrawn or revised to make technical 
changes to ensure conformity with appropriate terminology and cross-
references. Section 505G(k)(3) of the FD&C Act also provides that any 
such withdrawal or technical changes shall be made without public 
notice and comment and shall be effective upon publication through 
notice in the Federal Register (or upon such date as specified in such 
notice).
    FDA intends to issue a notice to withdraw the regulations 
establishing final monographs in title 21 of the CFR at a later date 
once all the relevant deemed final orders have been posted on FDA's OTC 
monographs@FDA web portal (i.e., 21 CFR parts 331, 332, 333, 335, 336, 
338, 340, 341, 343, 344, 346, 347, 348, 349, 350, 352, 355, 357, and 
358). Prior to the withdrawal of such regulations, the public should 
reference the OTC monographs posted in the OTC

[[Page 52478]]

Monographs@FDA portal at https://www.accessdata.fda.gov/scripts/cder/omuf/index.cfm, to the extent the corresponding deemed final order has 
been added to the portal. Additionally, in either the same notice or a 
separate notice in the Federal Register, pursuant to section 505G(k)(3) 
of the FD&C Act, FDA intends to withdraw certain portions of the 
regulations governing the OTC drug review, and to make certain 
technical changes.

IV. Paperwork Reduction Act of 1995

    Under section 505G(o) of the FD&C Act, the Paperwork Reduction Act 
of 1995 (Chapter 35 of title 44, United States Code) does not apply to 
collections of information made under section 505G of the FD&C Act. 
Therefore, clearance by the Office of Management and Budget under the 
Paperwork Reduction Act of 1995 is not required for collections of 
information, if any, in orders deemed to be final orders by section 
505G of the FD&C Act.

    Dated: September 16, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-20393 Filed 9-20-21; 8:45 am]
BILLING CODE 4164-01-P