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

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.

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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