[Federal Register Volume 64, Number 140 (Thursday, July 22, 1999)]
[Proposed Rules]
[Pages 39452-39454]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-18699]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 333

[Docket No. 99N-1819]
RIN 0910-AA01


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

AGENCY:  Food and Drug Administration, HHS.

ACTION: Proposed rulemaking.

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SUMMARY: The Food and Drug Administration (FDA) is issuing a notice of 
proposed rulemaking that would amend the final monograph for over-the-
counter (OTC) topical antifungal drug products. The amendment makes a 
minor change in the indications for these drug products. This proposal 
is part of the ongoing review of OTC drug products conducted by FDA.

DATES: Submit written comments by October 20, 1999; written comments on 
the agency's economic impact determination by October 20, 1999. See 
section IV of this document for the proposed effective date of a final 
rule based on this document.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

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 labeling 
in Sec. 333.250. Section 333.250(b)(1) contains the following 
introductory language for the indications statement: (Select one of the 
following: ``Treats,'' ``For the treatment of,'' ``For effective 
treatment of,'' ``Cures,'' ``For the cure of,'' ``Clears up,'' or 
``Proven clinically effective in the treatment of''). Section 
333.250(b)(2) contains similar language for products labeled for the 
prevention of athlete's foot.

II. The Panel's Recommendations

    The Advisory Review Panel on OTC Antimicrobial (II) Drug Products 
(the Panel) recommended the above labeling in its report on OTC topical 
antifungal drug products (47 FR 12480 at 12511, March 23, 1982). The 
Panel mentioned that there are several less common skin conditions that 
may affect the feet and the groin, cause symptoms that mimic athlete's 
foot and jock itch, and may be misdiagnosed as athlete's foot or jock 
itch. The Panel discussed common examples of such conditions: 
Candidiasis (a yeast infection), allergic contact dermatitis, bacterial 
infection of the feet (e.g., erythrasma), psoriasis, and hyperhidrosis 
(excessive perspiring) that may be associated with maceration of the 
skin and an inflammatory eruption known as dyshidrotic eczema (47 FR 
12480 at 12487). While the Panel discussed these conditions, it did not 
address appropriate treatment or consequences of misdiagnosis of any of 
these conditions.

III. The Agency's Tentative Conclusions and Proposal

    The agency recognizes that topical antifungal drug products will 
not cure or treat all conditions commonly thought by consumers to be 
athlete's foot or jock itch. Also, some of these conditions may have 
other etiologies. In addition to the conditions discussed by the Panel, 
consumers may erroneously consider a number of other conditions to be 
athlete's foot or jock itch. These include: Atopic dermatitis, irritant 
dermatitis, inverse pityriasis, scabies, and pediculosis pubis. All of 
these misdiagnosed conditions cannot be treated or cured by a topical 
antifungal drug product.
    Because consumers self select OTC topical antifungal drug products 
and do not diagnose, the agency believes that the labeling should be 
revised to more accurately inform them what they can expect from using 
these products. Therefore, the agency is proposing that the word 
``most'' be inserted in the allowed indications statements between the 
introductory phrase and the name of the condition(s) for which the 
product is to be used. This approach is consistent with the current 
labeling approved for OTC vaginal antifungal drug products under new 
drug applications (Ref. 1). That labeling states that the product 
``cures most vaginal yeast infections.''
    Accordingly, the agency is proposing to revise the indications in 
Sec. 333.250(b)(1)(i) and (b)(2)(i) to add the word ``most'' after the 
introductory parenthetical ``Select one of the

[[Page 39453]]

following'' choices and to add the word ``most'' in 
Sec. 333.250(b)(2)(ii) after the word ``up.'' The agency points out 
that this concept of ``treats most'' or ``cures most'' also needs to be 
used whenever a manufacturer uses the alternative labeling approaches 
allowed by 21 CFR 330.1(c)(2)(ii) or (c)(2)(iii) or whenever a general 
statement containing this information appears in the labeling of the 
product (e.g., on the principal display panel).

IV. Proposed Effective Date

    The agency is proposing that any final rule that may issue based on 
this proposal become effective 12 months after its date of publication 
in the Federal Register. The agency considers this new labeling an 
improvement to the current labeling, but recognizes that OTC topical 
antifungal drug products have used the current monograph labeling for 
almost 6 years. Therefore, to reduce relabeling costs for manufacturers 
of these products, the agency will consider an 18-month effective date 
for any final rule that may issue based on this proposal. This longer 
effective date would enable manufacturers to use up existing labeling 
and implement the new labeling in the normal course of reordering 
labeling for these products. The agency invites specific comment on 
this extended effective date.

V. Analysis of Impacts

    FDA has examined the impacts of this proposed rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612). 
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.
    Title II of the Unfunded Mandates Reform Act (2 U.S.C. 1501 et 
seq.) requires that agencies prepare a written statement and economic 
analysis 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 believes that this proposed rule is consistent with the 
principles set out in the Executive Order and in these two statutes. 
The purpose of this proposed rule is to make a minor revision in the 
indications for OTC topical antifungal drug products. This revision 
should improve consumers' self use of these drug products by better 
informing them about what they can expect from using the products.
    Manufacturers of these products will incur minor costs to relabel 
their products to revise the indications statement and, in some cases, 
other statements that appear in product labeling. The agency has been 
informed that relabeling costs of the type required by this proposed 
rule generally average about $2,000 to $3,000 per stock keeping unit 
(SKU) (individual products, packages, and sizes). The agency is aware 
of approximately 50 manufacturers that together produce about 200 SKU's 
of OTC topical antifungal drug products marketed under the monograph. 
There may be a few additional small manufacturers or products in the 
marketplace that are not identified in the sources FDA reviewed. 
Assuming that there are about 200 affected OTC SKU's in the 
marketplace, total one-time costs of relabeling would be $400,000 to 
$600,000. The agency believes the actual cost could be lower for 
several reasons. Most of the label changes will be made by private 
label manufacturers that tend to use simpler and less expensive 
labeling. In addition, the agency is considering and inviting public 
comment on an 18-month effective date for the final rule, rather than 
the standard 12-month effective date. This extended effective date may 
allow the new labeling to be implemented concurrently with the general 
labeling changes required by the new OTC drug labeling format (64 FR 
13254, March 17, 1999). The agency believes that these actions provide 
substantial flexibility and reductions in cost for small entities.
    The agency considered but rejected several labeling alternatives: 
(1) A shorter implementation period, and (2) an exemption from coverage 
for small entities. While the agency would like to have this new 
labeling in place as soon as possible, it considers a period less than 
1 year difficult for manufacturers to implement and not critical in 
this situation. The agency does not consider an exemption for small 
entities appropriate because consumers who use those manufacturers' 
products would not have the most recent information about these 
products.
    This analysis shows that this proposed rule is not economically 
significant under Executive Order 12866 and that the agency has 
undertaken important steps to reduce the burden to small entities. 
Nevertheless, some entities may incur some impacts, especially private 
label manufacturers that provide labeling for a number of the affected 
products. Thus, this economic analysis, together with other relevant 
sections of this document, serves as the agency's initial regulatory 
flexibility analysis, as required under the Regulatory Flexibility Act. 
Finally, this analysis shows that the Unfunded Mandates Reform Act does 
not apply to the proposed rule because it would not 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.

VI. Paperwork Reduction Act of 1995

    FDA tentatively concludes that the labeling requirements proposed 
in this document 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 proposed indications 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)).

VII. Environmental Impact

    The agency has determined under 21 CFR 25.30(h) that this action is 
of a type that is categorically excluded from the preparation of an 
environmental assessment because these actions, as a class, will not 
result in the production or distribution of any substance and therefore 
will not result in the production of any substance into the 
environment.

VIII. Request for Comments

    Interested persons may, on or before October 20, 1999, submit to 
the Dockets Management Branch (address above) written comments on the 
proposed regulation. Written comments on the agency's economic impact 
determination may be submitted on or before October 20, 1999. Three 
copies of all comments are to be submitted, except that individuals may 
submit one copy. Comments are to be identified with the docket number 
found in brackets in the heading of this document and may be 
accompanied by a supporting memorandum or brief. Received comments may 
be seen in the office above between 9 a.m. and 4 p.m., Monday through 
Friday.

[[Page 39454]]

IX. Reference

    The following reference has been placed on display in the Dockets 
Management Branch (address above) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.
    1. Approved labeling from new drug applications for OTC vaginal 
antifungal drug products.

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, it is 
proposed that 21 CFR part 333 be 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 333.250 is amended by revising paragraphs (b)(1)(i), 
(b)(2)(i), and (b)(2)(ii) to read as follows:


Sec. 333.250   Labeling of antifungal drug products.

* * * * *
    (b) *  *  *
    (1) *  *   * (i) (Select one of the following: ``Treats,'' ``For 
the treatment of,'' ``For effective treatment of,'' ``Cures,'' ``For 
the cure of,'' ``Clears up,'' or ``Proven clinically effective in the 
treatment of'') ``most'' (select one condition from any one or more of 
the following groups of conditions:
* * * * *
    (2) *  *  * (i) (Select one of the following: ``Clinically proven 
to prevent,'' ``Prevents,'' ``Proven effective in the prevention of,'' 
``Helps prevent,'' ``For the prevention of,'' ``For the prophylaxis 
(prevention) of,'' ``Guards against,'' or ``Prevents the recurrence 
of'') ``most'' (select one of the following: ``Athlete's foot,'' 
``athlete's foot (dermatophytosis),'' ``athlete's foot (tinea pedis),'' 
or ``tinea pedis (athlete's foot)'') ``with daily use.''
    (ii) In addition to the information identified in paragraph 
(b)(2)(i) of this section, the labeling of the product may contain the 
following statement: ``Clears up most athlete's foot infection and with 
daily use helps keep it from coming back.''
* * * * *

    Dated: July 14, 1999.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy.
[FR Doc. 99-18699 Filed 7-21-99; 8:45 am]
BILLING CODE 4160-01-F