[Federal Register Volume 67, Number 27 (Friday, February 8, 2002)]
[Rules and Regulations]
[Pages 5942-5943]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-3079]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 333

[Docket No. 99N-4063]
RIN 0910-AA01


Topical Antifungal Drug Products for Over-the-Counter Human Use; 
Amendment of Final Monograph

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is issuing a final rule 
amending the final monograph for over-the-counter (OTC) topical 
antifungal drug products to add the ingredient clotrimazole as 
generally recognized as safe and effective for the treatment of 
athlete's foot, jock itch, and ringworm. This final rule is part of 
FDA's ongoing review of OTC drug products.

DATES: This rule is effective March 11, 2002.

FOR FURTHER INFORMATION CONTACT: Gerald M. Rachanow, Center for Drug 
Evaluation and Research (HFD-560), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-2307.

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of September 23, 1993 (58 FR 49890), FDA 
published a final monograph for OTC topical antifungal drug products in 
part 333 (21 CFR part 333), subpart C. That monograph includes six 
antifungal active ingredients used for the treatment of athlete's foot, 
jock itch, and ringworm and one ingredient used for the prevention of 
athlete's foot. The monograph provides that two ingredients may contain 
professional labeling (may be provided to health professionals but not 
to the general public) for the treatment of superficial infections 
caused by yeast (Candida albicans).
    In the Federal Register of May 29, 2001 (66 FR 29059), FDA proposed 
to amend the final monograph to add the antifungal ingredient 
clotrimazole at a 1-percent concentration as generally recognized as 
safe and effective for the treatment of athlete's foot, jock itch, and 
ringworm. The agency discussed safety and effectiveness data for 
clotrimazole for these uses and noted it has been marketed OTC in the 
United States since 1989 under new drug applications (NDAs) in cream, 
lotion, and solution dosage forms, with a significant amount marketed 
in the United States and other countries since 1990.
    In response to the proposal, the agency received one comment, which 
is on public display in the Dockets Management Branch (HFA-305), 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852. The comment supported the 
agency's determination that clotrimazole has been marketed to a 
material extent and for a material time as a topical antifungal drug 
and that, based on the available data, it can be generally recognized 
as safe and effective for the treatment of athlete's foot, jock itch, 
and ringworm and included in the OTC drug monograph for this class of 
products.

II. The Agency's Final Conclusions

    The agency has determined that clotrimazole in a 1-percent 
concentration has been marketed to a material extent and for a material 
time as a topical antifungal drug. Based on the available data, it can 
be generally recognized as safe and effective for the treatment of 
athlete's foot (tinea pedis), jock itch (tinea cruris), and ringworm 
(tinea corporis) and included in the OTC drug monograph for this class 
of products. Therefore, the agency is adding clotrimazole 1-percent as 
new paragraph (g) in Sec. 333.210. Any product containing clotrimazole 
that is marketed under the monograph must use all of the labeling that 
is required by the final monograph (part 333, subpart C) and must 
follow the content and format requirements in 21 CFR 201.66.
    This final rule does not apply to clotrimazole marketed OTC as an 
antifungal agent in intravaginal drug products labeled for the 
treatment of vaginal yeast infections. The existing monograph for 
topical antifungal drug products does not contain any claims for 
intravaginal use.

III. Analysis of Impacts

    FDA has examined the impacts of the final rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612) (as 
amended by subtitle D of the Small Business Regulatory Fairness Act of 
1996 (Public Law 104-121)), and the Unfunded Mandates Reform Act of 
1995 (Public Law 104-4). Executive Order 12866 directs agencies to 
assess all costs and benefits of available regulatory alternatives and, 
when regulation is necessary, to select regulatory approaches that 
maximize net benefits (including potential economic, environmental, 
public health and safety, and other advantages; distributive impacts; 
and equity). Under the Regulatory Flexibility Act, if a rule has a 
significant economic impact on a substantial number of small entities, 
an agency must analyze regulatory options that would minimize any 
significant impact of the rule on small entities.
    Section 202(a) of the Unfunded Mandates Reform Act requires that 
agencies prepare a written statement of anticipated costs and benefits 
before proposing any rule that may result in an expenditure in any one 
year by State, local, and tribal governments, in the aggregate, or by 
the private sector, of $100 million (adjusted annually for inflation).
    The agency concludes that this final rule is consistent with the 
principles set out in the Executive order and in these two statutes. 
The final rule is not a significant regulatory action as defined by the 
Executive order and so is not subject to review under the Executive 
order. Further, since this final rule is not expected to result in any 
1-year expenditure that would exceed $100 million adjusted for 
inflation, FDA need not prepare additional analyses under the Unfunded 
Mandates Reform Act.
    The purpose of this final rule is to include clotrimazole 1-percent 
in the monograph for OTC topical antifungal drug products. This rule 
allows current manufacturers of these products to market their products 
under the OTC drug monograph instead of an NDA and enables other 
manufacturers who wish to market clotrimazole products OTC to enter the 
marketplace without having to obtain an NDA. In both cases, there will 
be cost savings from marketing without an NDA.
    When current manufacturers market these products under the OTC drug 
monograph, they should incur only minor costs to relabel their products 
to meet the monograph. Some manufacturers may have to add a warning 
that was included in the final monograph, but not required when

[[Page 5943]]

some products containing clotrimazole were approved for OTC marketing 
under an NDA. These manufacturers can make this change whenever they 
are ready to order new product labeling. Manufacturers have informed 
the agency that this type of relabeling cost generally averages about 
$2,000 to $3,000 per stock keeping unit (SKU) (individual products, 
packages, and sizes). Based on information in the agency's Drug Listing 
System, there are less than 10 manufacturers and distributors that 
together produce about 25 SKUs of OTC topical antifungal drug products 
that contain clotrimazole. Assuming that there are about 25 affected 
OTC SKUs in the marketplace, total one-time costs of relabeling would 
be $50,000 to $75,000. Because the manufacturers can make the changes 
when they are ready to reorder product labeling stock, the incremental 
costs of the added warning will, for the most part, be mitigated. In 
making this change, these manufacturers would save money by eliminating 
all costs associated with maintaining an NDA. Likewise, other 
manufacturers who now wish to market topical clotrimazole drug products 
will be able to enter the marketplace without the costs associated with 
an NDA. Their costs would involve the standard startup costs of any OTC 
drug marketed under the monograph.
    Because no small firms will be adversely affected, the agency 
certifies that this final rule will not have a significant economic 
impact on a substantial number of small entities.

IV. Paperwork Reduction Act of 1995

    FDA concludes that the labeling requirements for clotrimazole 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 
existing monograph labeling is 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)).

V. Environmental Impact

    The agency has determined under 21 CFR 25.31(a) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

VI. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the rule 
does not contain policies that have substantial direct effects on the 
States, on the relationship between the National Government and the 
States, or on the distribution of power and responsibilities among the 
various levels of government. Accordingly, the agency has concluded 
that the rule does not contain policies that have federalism 
implications as defined in the Executive order and, consequently, a 
federalism summary impact statement is not required.

List of Subjects in 21 CFR Part 333

    Labeling, Over-the-counter drugs.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
333 is amended as follows:

PART 333--TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER 
HUMAN USE

    1. The authority citation for 21 CFR part 333 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.

    2. Section 333.210 is amended by adding paragraph (g) to read as 
follows:


Sec. 333.210  Antifungal active ingredients.

* * * * *
    (g) Clotrimazole 1 percent.

    Dated: January 30, 2002.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 02-3079 Filed 2-7-02; 8:45 am]
BILLING CODE 4160-01-S