[Federal Register: February 8, 2002 (Volume 67, Number 27)]
[Rules and Regulations]
[Page 5942-5943]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr08fe02-7]
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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.
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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