Vaginal Drug Products for Over-the-Counter Human Use; Withdrawal of Advance Notice of Proposed Rulemaking

SUMMARY: The Food and Drug Administration (FDA) is issuing a notice to

withdraw the advance notice of proposed rulemaking of October 13, 1983

(48 FR 46694) that would have established conditions under which over-

the-counter (OTC) vaginal drug products are generally recognized as

safe and effective and not misbranded. FDA is issuing this notice of

withdrawal after considering the report and recommendations of the

Advisory Review Panel on OTC Contraceptives and Other Vaginal Drug

Products (the Vaginal Panel) and public comments on an advance notice

of proposed rulemaking that was based on those recommendations. This

action is being taken in part because the agency has determined that

some of the recommended labeling indications relate to cosmetic claims

and not drug claims. In addition, recommended labeling indications and

ingredients used for minor irritation, itching, or soreness are not

unique to the vaginal area and are already being considered in other

OTC drug rulemakings (e.g., antifungal, antimicrobial, and external

analgesic). Therefore, those ingredients and indications will be

considered in those other rulemakings, as appropriate.

FOR FURTHER INFORMATION CONTACT: William E. Gilbertson, Center for Drug

Evaluation and Research (HFD-810), Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857, 301-594-5000.

SUPPLEMENTARY INFORMATION: In the Federal Register of October 13, 1983

(48 FR 46694), FDA published, under Sec. 330.10(a)(6) (21 CFR

330.10(a)(6)), an advance notice of proposed rulemaking to establish a

monograph for OTC vaginal drug products, together with the

recommendations of the Vaginal Panel, which was the advisory review

panel responsible for evaluating data on the active ingredients in this

drug class. Interested persons were invited to submit comments by

January 11, 1984. Reply comments in response to comments filed in the

initial comment period could be submitted by March 19, 1984.

In accordance with Sec. 330.10(a)(10), the data and information

considered by the Vaginal Panel were put on public display in the

Dockets Management Branch (HFA-305), Food and Drug Administration, rm.

1-23, 12420 Parklawn Dr., Rockville, MD 20857, after deletion of a

small amount of trade secret information.

In this notice, FDA states for the first time its position on the

establishment of a monograph for OTC vaginal drug products based on the

Vaginal Panel's conclusions and recommendations on OTC vaginal drug

products, the comments received, and the agency's independent

evaluation of the Vaginal Panel's report. In the preamble to the

advance notice of proposed rulemaking for OTC vaginal drug products (48

FR 46694 at 46695), the agency expressed its concerns about: (1) The

ability of a woman to recognize the nature or cause of the symptom(s)

of vaginal itching, irritation, or soreness in order to determine which

kind of drug product to select to treat the condition, and (2) whether

1 to 2 weeks of self-medicating with an OTC drug product may pose an

unacceptable delay in seeking professional attention if the symptom(s)

of itching, irritation, or soreness are due to N. gonorrhoea,

Trichomonas, Candida, or other organisms that will not be eradicated by

topical therapy with nonantimicrobial OTC drug products. At that time,

no final agency decisions were made regarding the Vaginal Panel's

recommendations or the above stated concerns. The agency invited

specific comments on these issues.

In response to the advance notice of proposed rulemaking, four

drug manufacturers, two trade associations, nine consumers, four

medical associations, two pharmaceutical associations, three surgeons

general, one poison control center, three consumer groups, two

community health associations, and three practicing medical groups

submitted comments. Copies of the comments received are on public

display in the Dockets Management Branch (address above).

All OTC volumes cited throughout this document refer to the

submissions made by interested persons pursuant to the call-for-data

notice published in the Federal Register of May 16, 1973 (38 FR 12840)

or to additional information that has come to the agency's attention

since publication of the advance notice of proposed rulemaking. The

volumes are on public display in the Dockets Management Branch under

docket number 82N-0291.

I. The Agency's Tentative Conclusions on the Comments

A. General Comments

1. One comment contended that OTC drug monographs are

interpretive, as opposed to substantive, regulations. The comment

referred to statements on this issue submitted earlier to other OTC

drug rulemaking proceedings.

The agency addressed this issue in paragraphs 85 through 91 of the

preamble to the procedures for classification of OTC drug products,

published in the Federal Register of May 11, 1972 (37 FR 9464 at 9471

to 9472), and in paragraph 3 of the preamble to the tentative final

monograph for OTC antacid drug products, published in the Federal

Register of November 12, 1973 (38 FR 31260). FDA reaffirms the

conclusions stated in those documents. Court decisions have confirmed

the agency's authority to issue substantive regulations by rulemaking.

(See, e.g., National Nutritional Foods Association v. Weinberger, 512

F.2d 688, 696-698 (2d Cir. 1975) and National Association of

Pharmaceutical Manufacturers v. FDA, 487 F. Supp. 412 (S.D.N.Y. 1980),

aff'd, 637 F.2d 887 (2d Cir. 1981).)

2. One comment disagreed with the Vaginal Panel's statement that

``If an active ingredient is present in a therapeutic concentration,

the product is a drug, even if that product does not claim to produce

the effect which will result from the action of the therapeutically

effective ingredient * * *,'' (48 FR 46694 at 46701). The comment

argued that drug status of a product is determined only by its intended

use, not by the inclusion of certain ingredients, and the presence of a

certain ingredient in a product offered solely as a cosmetic does not

make the product a drug. The comment stated that FDA's policy

concerning drug versus cosmetic status has been stated in many

documents, including the procedural regulations governing the OTC drug

review (37 FR 9464 to 9475), and that the Vaginal Panel did not

properly apply this policy. The comment added that there is no

justification to apply a different principle to this rulemaking for

vaginal drug products. The comment requested that the term ``drug

product'' be used throughout the regulation wherever products are

specifically identified to emphasize the difference between cosmetic

and drug products, e.g., vaginal douche drug products.

The Federal Food, Drug, and Cosmetic Act (the act) provides the

statutory definitions that differentiate a drug from a cosmetic. A

``drug'' is defined in part as an article ``intended for use in the

diagnosis, cure, mitigation, treatment, or prevention of disease'' or

``intended to affect the structure or any function of the body * * *.''

(See 21 U.S.C. 321(g)(1)(B) and (C).) A ``cosmetic,'' on the other

hand, is defined as an article intended to be ``* * * applied to the

human body or any part thereof for cleansing, beautifying, promoting

attractiveness, or altering the appearance, * * *.'' (See 21 U.S.C.

321(i)(1).) Therefore, the agency agrees with the comment that the

intended use of a product is the primary determining factor as to

whether a product is a drug, a cosmetic, or both. This intended use may

be inferred from the product's labeling, promotional material,

advertising, and any other relevant factor. See, e.g., National

Nutritional Foods Ass'n v. Mathews, 557 F.2d 325, 334 (2d Cir. 1977).

The type and amount of ingredient(s) present in a product, even if

that product does not make explicit drug claims, must be considered in

determining its regulatory status. For example, the mere presence of a

pharmacologically active ingredient could make a product a drug even in

the absence of explicit drug claims. In these cases, the intended use

would be implied because of the known or recognized drug effects of the

ingredient (e.g., fluoride in a dentifrice).

The agency does not believe that it is necessary to use the term

``drug product'' throughout OTC drug monographs to distinguish between

drug and cosmetic products because the labeling in final monographs

applies only to products that fall within the statutory definition of a

drug, and does not apply to cosmetic products. However, if a product is

intended for both drug and cosmetic uses, e.g., cleansing and treating

a disease condition, it must conform to the requirements of the

applicable final monograph(s) for OTC drug products, as well as bear

appropriate labeling for cosmetic use in conformity with section 602 of

the act (21 U.S.C. 362) and the provisions of parts 701 and 740 (21 CFR

parts 701 and 740).

3. In response to the agency's specific request for comment on the

appropriateness of OTC drug products for treating the symptoms of

itching, irritation, and soreness in or around the vagina (48 FR 46694

at 46695), several comments stated that treating these symptoms with

OTC drug products is appropriate and rational therapy because women can

readily recognize these symptoms and the benefits to be derived from

the use of these drugs far outweigh any risks associated with their OTC

availability. A number of comments stated that there is no valid

medical basis to conclude, as was suggested by FDA in the preamble of

the advance notice of proposed rulemaking for OTC topical antifungal

drug products (47 FR 12480, March 23, 1982), that a serious health

hazard could result from self-treating the symptom of external feminine

itching. The comments contended that the likelihood of masking more

serious gynecological disorders such as gonorrhea or trichomoniasis, or

masking a more serious condition such as diabetes, was highly unlikely

provided the labeling of the products advises consumers to consult a

physician if symptoms worsen or persist for longer than 1 week. To

further support its contention that serious complications or delays in

proper medical diagnosis are not likely to occur if the symptoms of

external vaginal itching are treated with OTC drug products, one

comment cited the safe marketing experience of OTC hydrocortisone

products labeled with an indication that included ``external genital

(feminine) itching.'' The comment stated that none of the possible

problems projected, i.e., the masking of serious disease, the inability

to self-diagnose, and the presumed side effects of the drug, had

materialized since the marketing of OTC hydrocortisone began in 1979.

Several comments also argued that external vaginal itching and

irritation are not necessarily caused by infection, but can often be

caused by irritating clothing, sensitivities to cosmetics,

inappropriate hygiene, or other external factors.

In contrast, several comments stated that women should never self-

treat the symptoms of vaginal itching, irritation, or soreness because

they are not capable of self-diagnosis (i.e., specifically determining

an appropriate drug product to use based on various vaginal symptoms)

and should always be evaluated by a physician. The comments added that

self-treatment could unreasonably delay a proper diagnosis and could

even complicate it.

The agency notes that all of the products submitted to the Vaginal

Panel were intended for intravaginal use and with the exception of

vaginal contraceptives, the use of these OTC vaginal products, e.g.,

douches, suppositories, had been for the most part limited to cosmetic

purposes, e.g., cleansing, deodorizing, mechanical flushing. Thus, the

agency concludes that with the exception of indications relating to

minor itching, irritation, and soreness, all other recommended vaginal

monograph indications listed in the Vaginal Panel's report (48 FR 46694

at 46729) are cosmetic in nature or outside the scope of the OTC drug

review, e.g., ``Astringent,'' ``Removes vaginal discharge,'' ``Removes

vaginal secretions,'' ``Mild detergent action.'' Such indications for

vaginal products refer to a product's transitory cleansing effects

rather than to claimed therapeutic effects. (See drug/cosmetic

discussion in comment 2.) Therefore, except for some ``astringent''

claims (see comment 13), the agency considers these indications outside

the scope of the OTC drug review. The agency has no objection to the

continued availability of vaginal products bearing labeling claims

related to cleansing for cosmetic purposes, but does not believe that

these cosmetic products should be labeled or used for therapeutic

purposes except under the advice and supervision of a physician. As a

result of this withdrawal notice, manufacturers may need to relabel or

reformulate some products now or in the future. However, if

reformulation and/or relabeling are necessary, the cost will be minimal

because reformulation and relabeling will be required, in any event,

under other appropriate rulemakings.

The agency believes that consumers should have access to OTC drug

products to provide temporary relief of vaginal itching and irritation.

The agency recognizes that the safe marketing experience of

hydrocortisone, which has been available OTC since 1979 with an

indication that includes use on itchy anal and genital areas, provides

support that serious complications or delays in proper medical

diagnosis are not likely to occur if the symptom of vaginal itching is

treated with OTC drug products. Therefore, based on the available data

and information, the agency believes that the relief of vaginal

symptoms such as itching and irritation is an acceptable labeling claim

for certain OTC drug products.

As stated above, all of the products submitted to the Vaginal

Panel were intended for intravaginal use and concerns arose about self-

diagnosis, selection of an appropriate drug product, and self-treatment

of intravaginal disorders. The Fertility and Maternal Health Drugs

Advisory Committee (the Committee), in a meeting held June 14 and 15,

1990, discussed the proposal that vaginal fungicides be sold OTC for

the treatment of yeast (Candida) infections. Although a mechanism for

initial self-diagnosis was not considered, the Committee believed that

consumers could safely and adequately recognize and treat subsequent

intravaginal yeast infections after an initial diagnosis had been made

by a physician and recommended that vaginal antifungal drug products

whose safety was well-established be made available OTC with

appropriate labeling (Ref. 1). Based on the Committee's recommendations

and other available data, the agency has determined that certain OTC

drug products for intravaginal use to treat yeast infections or for the

relief of minor irritation, itching, and soreness can be safely used

OTC. However, as recommended above, the agency believes that antifungal

or other drug product ingredients for OTC intravaginal use are

appropriate only for those women who have previously been diagnosed by

a physician as having had the condition for which these drug products

are intended and are therefore able to subsequently recognize the

symptoms of the condition. The agency intends to discuss proposed

labeling and specific ingredients for OTC intravaginal use in an

amendment to the final monograph for OTC antifungal drug products in a

future issue of the Federal Register.

While a number of ingredients in OTC drug products could be used

in and around the vagina to relieve symptoms such as itching,

irritation, or soreness, the use of these ingredients is not specific

or unique to the vaginal area; i.e., they could be used topically to

relieve these same symptoms elsewhere on the body. For example,

antifungals, antipruritics, skin protectants, and astringents all have

potential for relieving symptoms occurring externally around the vagina

as well as on other parts of the body. It should be noted, however,

that certain drug product classes, e.g., antifungals, may be capable of

relieving itching and irritation by means of killing the cause of the

itch (e.g., yeast/fungus). These products would not be expected to be

routinely effective in treating ``itch'' due to other causes, e.g.,

poison ivy, eczema, insect bites, etc.

Also, in other OTC drug rulemakings, the agency has included, where

appropriate, the various conditions for which an ingredient is

considered generally recognized as safe and effective for OTC use in

one monograph. (See, for example, the discussion on hydrocortisone for

use in psoriasis (51 FR 27346 at 27360) and the discussion on menstrual

claims for internal analgesics (53 FR 46204 at 46209).) Therefore, for

those ingredients that are considered safe and effective for use in

relieving conditions in and around the vagina, the agency believes it

is more appropriate to include a vaginal claim in the applicable OTC

drug monograph rather than to have a separate monograph for ingredients

and claims related to vaginal use only. (See, for example, ``external

feminine itching'' claims for hydrocortisone products included in the

tentative final monograph for OTC external analgesic drug products (48

FR 5852 at 5868).)

Therefore, based on the discussion above, the agency is

withdrawing the advance notice of proposed rulemaking for OTC vaginal

drug products, which indicated the intention to create new subpart B of

proposed part 351. This withdrawal reflects the agency's intention

regarding the language previously published for potential codification

in part 351, but does not negate or reject the advisory panel's report.

Specific vaginal claims for the various pharmacologic classes of

ingredients will be considered in other appropriate monographs. Because

the issues raised by the comments may significantly affect these other

OTC drug rulemakings, the agency believes it is useful to respond to

these issues in this document. These issues and the agency's response

to them will also be discussed in other appropriate OTC drug

rulemakings. Interested persons may, at that time, submit comments to

the applicable rulemakings.

Reference

(1) Summary Minutes of the Fertility and Maternal Health Drugs

Advisory Committee, dated June 14-15, 1990, in OTC Vol. 11BTFM.

4. Several comments supported the recommendations of the Advisory

Review Panel on OTC Antimicrobial II Drug Products (the Antimicrobial

II Panel) that proposed a prescription to OTC switch of certain topical

antifungal drugs for treating external feminine itching associated with

a yeast infection (47 FR 12480). These comments stressed that candidal

(yeast) infections of the vagina are extremely common and recurrent and

that women can recognize with reasonable certainty when they have a

yeast infection, especially if they have had one before.

The agency is aware that all three OTC advisory review panels

charged with reviewing products that could be used in or around the

vagina concluded that vaginal infections could not be self-diagnosed or

self-treated. The panels' conclusions are consistent with FDA policy

that infections in general should not be self-diagnosed by consumers or

self-treated with OTC drug products. The only exception to this general

policy is the OTC use of topical antifungals for treating athlete's

foot, jock itch, and ringworm. The Antimicrobial II Panel that reviewed

topical antifungal drug products and FDA have determined that these

infections are so common and recurrent that they are amenable to self-

diagnosis and treatment. In addition, the Antimicrobial II Panel

recommended that haloprogin, miconazole, and nystatin be switched from

prescription to OTC status for external feminine itching associated

with a yeast infection. The Antimicrobial II Panel did not recommend

these ingredients for treatment of the infection itself, but believed

that OTC availability of these ingredients would be beneficial in

providing rapid symptomatic relief of itching. The issue of consumer

diagnosis of recurrent infections after appropriate physician diagnosis

of the initial infection was not discussed during any of the panels'

consideration of this issue.

The Antimicrobial II Panel also recommended that haloprogin,

miconazole, and nystatin be available OTC for the treatment of

superficial skin infections caused by yeast (Candida) (47 FR 12480 at

12565) However, the agency concluded in the tentative final monograph

for OTC antifungal drug products (54 FR 51136 at 51140) that no

antifungal ingredient should be labeled for OTC use for the treatment

of cutaneous candidiasis. However, the agency stated that cutaneous

candidiasis claims for effective antifungal ingredients could

appropriately be included in professional labeling. As stated in

comment 3, in light of the recommendations of the Committee, the agency

has reevaluated its position on the availability of antifungal drug

products for OTC treatment of vaginal yeast (Candida) infections. The

antifungal ingredients clotrimazole and miconazole nitrate, at specific

concentrations, have been approved for OTC intravaginal use, for

specific indications, under new drug applications (Refs. 1 and 2).

References

(1) Labeling from NDA 18-052 for Gyne-Lotrimin Vaginal Cream,

in OTC Vol. 11BTFM, Docket No. 82N-0291, Dockets Management Branch.

(2) Labeling from NDA 17-450 for Monistat 7 Vaginal Cream, in

OTC Vol. 11BTFM, Docket No. 82N-0291, Dockets Management Branch.

5. One comment disagreed with the Vaginal Panel's recommendation

that ingredients classified as Category II for use in OTC vaginal drug

products be removed automatically from vaginal cosmetic products (48 FR

46694 at 46710). The comment stated that this action is unwarranted

because the safety of cosmetic ingredients is assured by the

manufacturers, who consider not only the scientific analyses done by

the OTC advisory panels and FDA, but also additional published and

unpublished data that may not have been reviewed by the panels. The

comment also contended that the specific use of an ingredient in a

cosmetic may differ from its use in a drug product.

The agency notes that the Vaginal Panel made this recommendation

in discussing Category II combination vaginal drug products. The

Vaginal Panel recommended to the agency that any Category II ingredient

that causes a combination product to be placed in Category II for

safety reasons be removed from products regardless of whether they are

intended for use as a drug or a cosmetic because of concerns about

protecting consumers from unsafe ingredients. While sharing the Vaginal

Panel's concern, the agency agrees with the comment that automatic

removal of Category II drug ingredients from cosmetic products is not

warranted because other factors need to be considered. For example,

while an ingredient may not be safe in one concentration for use as a

drug, it may be acceptable for use at a lower concentration in a

cosmetic product. However, the agency will look carefully at any

ingredients that are present in cosmetic products when those

ingredients have been found unsafe for use in OTC drug products. FDA is

prepared to take appropriate regulatory action in preventing the use of

ingredients in cosmetic products when a potential health hazard is

known to exist with their continued use. (See 21 CFR part 700--subpart

B.)

6. One comment stated that the Vaginal Panel ``may have

inappropriately suggested the need for effectiveness testing for

vaginal drug product final formulations'' (48 FR 46694 at 46724 and

46725). The comment stressed that the OTC drug review is intended to be

an active ingredient review and that testing is not necessary for final

formulations of these products.

In discussing testing guidelines for vaginal douche products, the

Vaginal Panel simply stated that it did not require effectiveness

testing for douches that make only cosmetic claims, e.g.,

``cleansing.'' However, the Vaginal Panel recommended that

effectiveness testing should be required for those ingredients in

vaginal douches that make drug claims, e.g., ``relieving irritation.''

As discussed in comment 3, the agency is withdrawing the advance

notice of proposed rulemaking for OTC vaginal drug products and is

referring consideration of specific claims and ingredients for use in

and around the vagina to other appropriate OTC drug rulemakings. Any

necessary final formulation testing will also be discussed in those

rulemakings, e.g., ingredients used in vaginal antiseptic drug

products.

B. Comments on Active Ingredients

7. Two comments objected to the Vaginal Panel's conclusion that

data are insufficient to prove the safety of quaternary ammonium

compounds (i.e., benzalkonium chloride, benzethonium chloride, and

methylbenzethonium chloride) for vaginal use (48 FR 46694 at 46717).

The comments stated that although the Vaginal Panel's concern was based

on published literature reports where the use of these compounds was

associated with infections caused by Pseudomonas, it was not

scientifically sound to use these reports to conclude that a safety

problem exists. The comments mentioned that the Vaginal Panel failed to

state that these reports resulted from the contamination of solutions

that were employed in laboratory and hospital settings to sterilize

medical devices used in urinary and cardiac catheterization or

cystoscopic or related invasive procedures. Such procedures are usually

conducted on patients whose normal body defenses have been compromised.

Because Pseudomonas infections occur primarily in debilitated patients

and Pseudomonas does not cause vulvovaginitis, the comments stated that

it is scientifically inappropriate to cite these reports and through

extrapolation conclude that the use of quaternary ammonium compounds in

vaginal drug products presents a health hazard to normal individuals.

The comments cited several references (Refs. 1 through 7) to show

that the Vaginal Panel's concerns with respect to vaginal contamination

by Pseudomonas in the presence of quaternary ammonium compounds are not

supported by the weight of scientific data. The comments added that

extensive toxicological studies on these compounds have been published

(Ref. 8). The comments requested the agency to affirm the safety of

quaternary ammonium compounds and classify them as Category I for use

in relieving minor irritations of the vagina.

Another comment stated that quaternary ammonium compounds

historically have been included in vaginal products as preservatives

and that these ingredients should be allowed to continue to be used for

this purpose.

The agency agrees with the comments' reasoning that the reports

cited by the Vaginal Panel about Pseudomonas infections are not

adequate to conclude that the use of quaternary ammonium compounds in

OTC vaginal drug products may present a health hazard to normal

individuals. The agency has no objection to the continued use of

quaternary ammonium compounds as preservatives in OTC drug and cosmetic

products provided the products are manufactured in accordance with

established procedures that assure the adequacy of preservative systems

and microbial limits of products.

With respect to the use of quaternary ammonium compounds as active

ingredients in OTC vaginal drug products for relieving symptoms of

itching, irritation, or soreness, the Vaginal Panel stated that it was

unaware of any data that demonstrated effectiveness for these uses (48

FR 46694 at 46718). The comments did not include any new data, and the

agency is unaware of any such data.

As explained in comment 3, the agency has decided to consider

specific vaginal claims for the various ingredients in other

appropriate rulemakings. Quaternary ammonium compounds are included as

Category I ingredients in the tentative final monograph for OTC first

aid antiseptic drug products, published in the Federal Register of July

22, 1991 (56 FR 33644). Any comments or new data received regarding

specific vaginal use of quaternary ammonium compounds will be

considered by the agency in the rulemaking for OTC topical

antimicrobial drug products.

References

(1) Forkner, Jr., C. E., ``Pseudomonas aeruginosa Infections,''

in ``Modern Medical Monographs,'' vol. 22, edited by I. S. Wright

and R. H. Orr, Gruen and Stratton, New York, pp. 71-73, 1960.

(2) Gardner, H. L., and R. H. Kaufman, ``Nonvenereal Bacterial

Vulvovaginitides,'' in ``Benign Diseases of the Vulva and Vagina,''

C. V. Mosby Co., St. Louis, p. 212, 1969.

(3) Charles, D., ``Major Problems in Obstetrics and

Gynecology,'' W. D. Saunders Co., pp. 4-5, 1980.

(4) Pidieu, C. M., ``The Vulva, Major Problems in

Dermatology,'' vol. 5, edited by A. Rook, W. B. Saunders Co.,

Philadelphia, p. 99, 1979.

(5) Monif, G. R. F., ``Infectious Disease in Obstetrics and

Gynecology,'' 2d edition, Harper and Row, Hagerstown, MD, pp. 524-

525, 1982.

(6) Mead, P. B., and D. W. Gump, ``Antibiotic Therapy In

Obstetrics and Gynecology,'' in ``Clinical Obstetrics and

Gynecology,'' edited by H. J. Osofsky and G. Schaefer, Harper and

Row, Hagerstown, MD, pp. 109-129, 1976.

(7) Gardner, A. et. al., ``Long Term Multicenter Trial with Ta-

Ro-Cap, A New Spermicidal Product,'' Contraception, 20:489-495,

1979.

(8) Finnegan, J. K., and J. B. Dienna, ``Toxicity of

Quaternaries,'' Soap and Sanitary Chemicals, February 1954.

8. One comment supported the Vaginal Panel's Category I

classification of potassium sorbate (48 FR 46694 at 46704) and

disagreed with the agency's conclusion that potassium sorbate is a new

drug because it has not been marketed as a drug to a material extent

and for a material time in the United States (48 FR 46694 at 46695).

The comment stated that a product containing potassium sorbate had been

marketed for over 2 years and that this ingredient is generally

recognized as safe and effective for the treatment of minor vaginal

itching and irritation and should be included as a monograph

ingredient. The comment contended that potassium sorbate is safe

because it was so recognized by the Vaginal Panel, and because of the

lack of ``any report of major side effects, adverse reaction or

complaint'' while 14 million units of a product containing this

ingredient were sold for over 2 years before marketing was

discontinued. The comment argued that potassium sorbate is effective

because it was so recognized by the Vaginal Panel based on two adequate

and well-controlled clinical studies (48 FR 46694 at 46704). The

comment added that this ingredient has been historically used by

physicians for treatment of vaginal itching and irritation, and that

this professional use constitutes use ``for a material time and to a

material extent.'' The comment also argued that potassium sorbate is

safer than povidone-iodine, which the Vaginal Panel recommended as a

Category I ingredient for these uses. The comment concluded that

potassium sorbate is not a new drug because of its historical use and

because of its marketing history, and should be placed in Category I as

a monograph ingredient.

In the preamble to the Vaginal Panel's report (48 FR 46694 at

46695), the agency stated its opinion as follows:

The agency is not aware of the marketing of any drug product

containing potassium sorbate as an active ingredient prior to

adoption of the Panel's report, although at least one product has

entered the marketplace since that time. Because potassium sorbate

has not been marketed as a drug to a material extent and for a

material time in the United States, the agency considers this

ingredient to be a new drug within the meaning of section 201(p) of

the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321(p)). It may

not be marketed until FDA has approved a new drug application (NDA)

for such use.

The agency has not at this time changed its position on potassium

sorbate for the treatment of minor vaginal itching and irritation.

However, issues about the agency's interpretations regarding marketing

to a ``material extent'' and for a ``material time'' as threshold

criteria for inclusion of an ingredient in the OTC drug review have

been raised in a number of rulemakings. Citizen petitions (Refs. 1 and

2) have been filed requesting the agency to change its longstanding

position on these threshold criteria, especially with regard to

permitting foreign marketing to satisfy the material time and extent

criteria. The agency intends to address the material time and extent

issues in a consolidated response in a future issue of the Federal

Register.

References

(1) Comments No. CP2, CP3, and CP4 Docket No. 78N-0038, Dockets

Management Branch.

(2) Comment No. CP1, Docket No. 92P-0309, Dockets Management

Branch.

9. One comment requested that Category I approval of povidone-

iodine as an active ingredient for the relief of minor irritations of

the vagina be extended to include a vaginal suppository as well as a

douche dosage form. The comment stated that the absorption potential

with a suppository dosage form should be no greater than with a vaginal

douche, and that there is no basis for making a distinction between a

suppository and a douche dosage form with respect to effectiveness.

In response to a comment comparing the relative safety of

potassium sorbate to povidone-iodine (see comment 8), one comment

contended that the safety and effectiveness questions raised by the

other comment with respect to povidone-iodine were superficial and

erroneous and were in disregard of the facts. The comment stated that

over 1,000 published studies and over 30 years of experience

demonstrate the safety and effectiveness of povidone-iodine and confirm

its Category I status for vaginal use as a douche.

Povidone-iodine in various formulations for vaginal use, i.e.,

douche and gel, was originally reviewed under the FDA Drug Efficacy

Study Implementation (DESI). The DESI panel concluded that povidone-

iodine was effective as a douche, i.e., for cleansing purposes, and

that povidone-iodine could offer some partial or temporary relief of

itching and odor when infection was present. Only the douche

formulation was deferred for consideration to the OTC drug review. In

the Federal Register of October 13, 1983 (48 FR 46694 at 46705), the

Vaginal Panel reviewed the povidone-iodine douche product (0.15 to 3

percent) and placed it in Category I for the relief of minor

irritations of the vagina. The Vaginal Panel did not review povidone-

iodine in a suppository dosage form because no data on this dosage form

were submitted. However, the Vaginal Panel did consider the suppository

dosage form for claims relating to relief of minor irritation, and

reduction of number of pathogenic microorganisms, and stated that such

claims must be substantiated by testing (48 FR 46694 at 46702). The

safety and effectiveness of povidone-iodine for the relief of itching

and minor irritation in and around the vagina will be discussed by the

agency in the rulemaking for OTC topical antimicrobial drug products in

a future issue of the Federal Register. (See also discussion in comment

17 regarding professional labeling claims.)

C. Comments on Labeling

10. One comment objected to the Vaginal Panel's recommendation

that OTC drugs be labeled with the components of perfumes that are

included in the products. The comment explained that fragrances and

flavors are often made up of dozens of ingredients and that to list

each of these individually would be a practical impossibility;

furthermore, the composition of a perfume is a significant trade

secret. The comment pointed out that this issue had been considered and

rejected by Congress and FDA on several occasions over the past decade,

and concluded that there was no reason whatsoever to change these

previous decisions.

Because section 502(e) of the act (21 U.S.C. 352(e)) specifies the

requirements for the labeling of active and inactive ingredients in

drug products, there is no need to include such requirements in an OTC

drug monograph. However, the agency notes that although section 502(e)

of the act does not require the complete identification of all inactive

ingredients in the labeling of OTC drugs, it does require the

disclosure of certain ingredients, whether included as active or

inactive components in a drug product. Although FDA does not require

the inclusion of all the inactive ingredients in OTC drug product

labeling, the agency urges manufacturers to list all inactive

ingredients voluntarily as recommended by the Vaginal Panel. This

information will enable the consumer with known allergies or

intolerance to certain ingredients to select products with increased

confidence of safe use.

After the Vaginal Panel made its recommendations to FDA, the

Nonprescription Drug Manufacturers Association (NDMA) (formerly the

Proprietary Association), the trade association that represents OTC

drug manufacturers who reportedly market 90 to 95 percent of all OTC

drug products sold in the United States, implemented a program under

which its member companies voluntarily list inactive ingredients in the

labeling of OTC drug products under guidelines established by NDMA

(Ref. 1). Although these guidelines do not specify the listing of each

ingredient contained in the fragrance or perfume in the product, they

do provide for such inactive ingredients as flavors and fragrances to

be listed as ``flavors'' and ``fragrances.'' Hence, the consumer with

known allergies or intolerances to such inactive ingredients as

flavors, fragrances, or perfumes would be generally aware of their

inclusion in certain OTC drug products. The agency commends these

voluntary efforts and urges all OTC drug manufacturers to label their

products voluntarily in accordance with NDMA's guidelines.

Reference

(1) ``Proprietary Association Adopts Voluntary Disclosure of

Inactive Ingredients,'' news release, The Proprietary Association,

Washington, May 14, 1984, copy included in OTC Vol. 11BTFM, Docket

No. 82N-0291, Dockets Management Branch.

11. Several comments argued that FDA cannot legally and should

not, as a matter of policy, prescribe exclusive lists of terms from

which statements of identity and indications for use of OTC drug

products must be drawn and prohibit alternative OTC labeling

terminology which is truthful, not misleading, and intelligible to the

consumer to describe such indications. Two comments argued that such a

restriction is an unconstitutional restriction of commercial speech and

exceeds FDA's authority. One comment stated that this ``exclusivity

policy'' is not warranted as a matter of sound public policy, and

recommended that FDA follow a guideline labeling policy instead of an

exclusive one. One comment objected that the advance notice of proposed

rulemaking was more restrictive in limiting the ``statements of

identity'' than is the regulation in Sec. 201.61 (21 CFR 201.61). The

comment urged the agency to allow manufacturers the alternative ways of

describing the statements of identity that are allowed in Sec. 201.61.

In the Federal Register of May 1, 1986 (51 FR 16258), the agency

published a final rule changing its labeling policy for stating the

indications for use of OTC drug products. Under Sec. 330.1(c)(2) (21

CFR 330.1(c)(2)), the label and labeling of OTC drug products are

required to contain in a prominent and conspicuous location, either:

(1) The specific wording on indications for use established under an

OTC drug monograph, which may appear within a boxed area designated

``APPROVED USES''; (2) other wording describing such indications for

use that meets the statutory prohibitions against false or misleading

labeling, which shall neither appear within a boxed area nor be

designated ``APPROVED USES''; or (3) the approved monograph language on

indications, which may appear within a boxed area designated ``APPROVED

USES,'' plus alternative language describing indications for use that

is not false or misleading, which shall appear elsewhere in the

labeling. All other OTC drug labeling required by a monograph or other

regulation (e.g., statement of identity, warnings, and directions) must

appear in the specific wording established under the OTC drug monograph

or other regulation where exact language has been established and

identified by quotation marks, e.g., Secs. 201.63 or 330.1(g).

12. One comment stated that FDA's exclusivity policy is a drug

labeling policy that has no application to cosmetic claims appearing in

the labeling of products that are both cosmetics and drugs.

The agency agrees with the comment that the labeling restrictions

in OTC drug monographs apply only to products that fall within the

statutory definition of ``drugs'' and not to cosmetic products. This

distinction between drugs and cosmetics is discussed in comment 3.

Final OTC drug monographs cover only the drug use of the active

ingredients listed therein. The concentration range, limitations,

statements of identity, indications, warnings, and directions

established for these ingredients in a monograph do not apply to the

use of the same ingredients in products intended solely as cosmetics.

However, if a product is intended for both drug and cosmetic use, it

must conform to the requirements of the applicable final monograph(s).

In addition to any indications allowed for OTC drug products bearing

claims for vaginal use, such products may also bear appropriate

labeling for cosmetic use(s), in conformity with section 602 of the act

and the provisions of parts 701 and 740. In accordance with the final

rule on the agency's exclusivity policy (51 FR 16258, May 1, 1986),

cosmetic claims may not appear within the boxed area designated

``APPROVED USES.'' As discussed at 51 FR 16258 at 16264 (paragraph 14),

cosmetic claims may appear elsewhere in the labeling but not in the box

should manufacturers choose the labeling alternative provided in

Sec. 330.1(c)(2)(i) or (c)(2)(iii) for labeling cosmetic drug products.

13. One comment agreed with the Vaginal Panel's conclusions that

the terms ``cleansing,'' ``producing soothing and refreshing effects,''

and ``deodorizing'' (as used in the definitions of vaginal douche and

vaginal suppository) are cosmetic claims (48 FR 46694 at 46701). The

comment urged the agency to accept the Vaginal Panel's recommendation.

In addition to the claims above, another comment also considered the

claim ``producing an astringent effect'' to be a cosmetic claim. The

comment argued that these claims do not make a vaginal product into a

drug, that it is legally inappropriate to include them in the

definitions of these products in proposed Sec. 351.103 of the

monograph, and that they should be removed from the definitions section

and anywhere else they appear in the document.

The agency agrees that cosmetic claims should not be included in

OTC drug rulemakings. Therefore, the cosmetic claims ``cleansing,''

``soothing,'' ``refreshing,'' and ``deodorizing'' will not be included

in OTC drug monographs. The agency believes, however, that astringency

can be either a drug claim or a cosmetic claim, depending on the

intended use and labeling of the product. For example, astringent

products intended and labeled for the relief of minor vaginal

irritation or reduction in local edema would be considered as drugs,

while astringent products intended and labeled for a refreshing effect

would be considered as cosmetics. A product making both claims would be

both a drug and a cosmetic. Thus, the agency will consider the intended

use in determining whether it is a cosmetic, a drug, or both (see also

comment 3).

14. One comment stated that the Vaginal Panel's categorization of

cosmetic claims as Category II drug claims is inappropriate because

cosmetic claims are not within the jurisdiction of the OTC drug review.

The comment contended that the following claims were inappropriately

classified as Category II drug claims by the Vaginal Panel (48 FR 46694

at 46710) because these claims are really cosmetic claims:

Effectively cleanses

Effectively deodorizes

Cleans thoroughly

Destroys odor

Continued vaginal cleanliness

Cleanses more thoroughly than other douches

Removes contraceptive jellies and creams

Changes water into a cleansing solution

Complete feminine hygiene

Personal hygiene

Hypoallergenic

Feminine hygiene

Intimate cleanliness

Prevents disagreeable odors

Effective germ killer

Routine feminine hygiene

Completely refreshed

The comment also contended that the Vaginal Panel placed the

following ``other product quality claims'' in Category II and that

these claims do not belong in the rulemaking because they are not drug

claims:

Fortified triple strength

Scientifically balanced formula

Intimately understood

Changes water into a cleansing solution

Naturally safe ingredients

Formula like the natural environment in

your body

Ph of 3.5

Effective liquid

Nonacid

Intended for all women who want to enjoy extra confidence in meeting

people

As with all vaginal douches, its function is not to cover up odor

Unlike spray deodorants which offer less protection

Complete feminine daintiness

Clinically tested

Dainty and feminine

Gentle

Safe for delicate membranes

Contains only the mildest ingredients

Completely compatible with normal vaginal environment

Buffered to control a normal vaginal pH

Stating that the Vaginal Panel did not provide a reason for its

recommendation, the comment requested that reference to these claims be

deleted at the next stage of the rulemaking.

Although there will not be another stage in this rulemaking, the

comment's concerns regarding these label terms are relevant to vaginal

claims for OTC drug products subject to other OTC drug monographs.

Therefore, the agency believes it is pertinent to address the comment's

concerns.

The OTC drug review establishes conditions under which some OTC

drugs are generally recognized as safe and effective and not

misbranded. Two principal conditions examined during the review are

allowable ingredients and allowable labeling. FDA has determined that

it is not practical--in terms of time, resources, and other

considerations--to set standards for all labeling found in OTC drug

products. Accordingly, OTC drug monographs regulate only labeling

related in a significant way to the safe and effective use of covered

products by lay persons. OTC drug monographs establish allowable

labeling for the following items: product statement of identity; names

of active ingredients; indications for use; directions for use;

warnings against unsafe use, side effects, and adverse reactions; and

claims concerning mechanism of drug action. The agency agrees with the

comment that some of the claims listed above are either solely cosmetic

claims or do not relate in a significant way to the safe and effective

use of OTC vaginal drug products and, therefore, are outside the scope

of the OTC drug review. Although these terms are considered outside the

scope of the review, if used in the labeling of OTC drug products they

will be evaluated by the agency on a product-by-product basis, under

the provision of section 502 of the act relating to labeling that is

false or misleading. Moreover, any term that is outside the scope of

the review, even though it is truthful and not misleading, may not

appear in any portion of the labeling required by a monograph and may

not detract from such required information. However, terms outside the

scope of a monograph may be included elsewhere in the labeling,

provided they are not false or misleading. In addition, as explained in

comment 2, the labeling restrictions in final monographs apply only to

products that fall within the statutory definition of a drug, and not

to cosmetic products. However, if a product is intended for both drug

and cosmetic use, it must conform not only to the requirements of the

applicable final monographs, but also to section 602 of the act and the

regulations in parts 701 and 740.

15. One comment contended that the use of the adjective

``vaginal'' modifying ``douche'' in the statement of identity in

Sec. 351.152(a) is unnecessary and superfluous because, in common

language usage, the word ``douche'' has become synonymous with vaginal

use. The comment added that the agency has codified this class of

products as ``douche preparations'' in 21 CFR 369.20. The comment

requested that the statement of identity allow for synonyms for

``vaginal douche'' such as ``feminine douche,'' ``disposable douche,''

and ``douche.'' The comment argued that the term ``vaginal douche'' may

be too sensitive for certain advertising media and that the requested

synonyms plus the accompanying labeling would clearly define the

product as intended for vaginal use only.

The agency recognizes the sensitivity to use of the word

``vaginal'' and will take this into consideration in developing

labeling in the appropriate OTC drug monographs. (See, e.g., the

labeling developed for hydrocortisone in the tentative final monograph

for OTC external analgesic drug products (48 FR 5852 at 5868).)

16. One comment objected to the Vaginal Panel's recommendation in

proposed Sec. 351.152(b) that the two statements ``Keep this and all

drugs out of the reach of children'' and ``DOES NOT PREVENT PREGNANCY''

appear on the principal display panel of OTC vaginal drug products. The

comment argued that including such statements on the principal display

panel is contrary to labeling requirements in other OTC drug

regulations now in effect in that statements such as these are

generally required to be displayed in a warnings section next to the

directions for use. The comment further argued that vaginal douche

products have not been shown less safe than or different from other OTC

drug products to the extent that would necessitate inclusion of

separate warning statements. The comment requested that the Vaginal

Panel's recommended that proposed Sec. 351.152(b) be deleted and that

these statements be included with the recommended label warnings in

proposed Sec. 351.154(a).

The agency agrees with the comment that special placement of these

warning statements on the principal display panel is unwarranted. The

Vaginal Panel recommended that the statement ``Keep this and all drugs

out of the reach of children'' appear on the principal display panel

because the attractiveness and colorful appearance of many vaginal drug

products may encourage children to open and consume the contents (48 FR

46694 at 46708). The agency is unaware of any evidence that OTC vaginal

drug products are any more attractive or more likely to be opened and

consumed by children than other OTC drug products. Therefore, the

agency has determined that there is no need for special placement of

this general warning statement in the labeling of OTC vaginal drug

products. Because existing regulations in Sec. 330.1(g) (21 CFR

330.1(g)) already require all OTC drugs to contain the warning ``Keep

this and all drugs out of the reach of children,'' there is no need to

include this warning in individual OTC drug monographs.

However, because the Vaginal Panel was concerned that there is a

commonly held misconception by some people that douching prevents

pregnancy (48 FR 46694 at 46708), the agency encourages manufacturers

to voluntarily place the warning ``DOES NOT PREVENT PREGNANCY'' in the

labeling of vaginal douche products. The agency will discuss vaginal

drug product labeling regarding prevention of pregnancy and sexually

transmitted diseases as part of the rulemaking for OTC antifungal drug

products in a future issue of the Federal Register.

17. One comment urged deletion of the Vaginal Panel's recommended

professional labeling statement in proposed Sec. 351.180(b)(3), which

reads: ``The use of povidone-iodine as a douche may cause a transient

rise of serum protein-bound iodine.'' The comment argued that in view

of the Vaginal Panel's conclusion that a transient rise in serum

protein-bound iodine levels (observed in some individuals) does not

affect the safety of the drug and has not been shown to have clinical

significance with respect to thyroid function (48 FR 46694 at 46705),

the statement is unwarranted. The comment added that inclusion of such

a statement in professional labeling is misleading because it directs

unwarranted emphasis to an essentially meaningless event.

The comment also stated that if the agency decides not to delete

this statement, the statement should be amended to read as follows:

``While not affecting its safety, the use of povidone-iodine as a

douche may cause a transient rise in serum protein-bound iodine in some

individuals. Such transient elevation returns to normal within 7 to 30

days and there is no evidence that this has clinical significance with

respect to thyroid function.'' The comment contended that this revised

statement would present the full clinical significance of the rise in

serum protein-bound iodine according to the Vaginal Panel's stated

findings.

As discussed in comment 9, the agency intends to consider

povidone-iodine for vaginal use in the rulemaking for OTC topical

antimicrobial drug products in a future issue of the Federal Register.

In the tentative final monographs in which povidone-iodine is a

Category I ingredient (antifungal (54 FR 51136, December 12, 1989) and

first aid antiseptic (56 FR 33644, July 22, 1991)), a statement

regarding the transient rise in protein-bound iodine associated with

the use of povidone-iodine has not been included in professional

labeling. Any other professional labeling associated with vaginal use

of povidone-iodine will be considered as part of the antimicrobial

rulemaking and will not be further considered here.

D. Comments on Combinations

18. One comment requested that the Vaginal Panel's recommended

list of permitted combinations in proposed Sec. 351.120 be amended to

provide for combinations of one Category I ingredient from any two,

three, or four of the various pharmacologic classes. The comment stated

that there is adequate precedent in the OTC drug review for combining

Category I ingredients from one pharmacological class with Category I

ingredients from another pharmacological class, without the necessity

of elaborate testing of the combination.

As explained in comment 3, the agency is withdrawing the advance

notice of proposed rulemaking for OTC vaginal drug products and is

referring consideration of specific vaginal claims to other appropriate

OTC drug rulemakings. Likewise, combinations of ingredients for vaginal

claims will be considered in those respective rulemakings and will not

be considered here.

19. The agency recognizes that the Vaginal Panel recommended some

professional labeling indications for several of the ingredients it

reviewed. (See Proposed Sec. 351.180, 48 FR 46694 at 46729.) For a

combination product containing the ingredients dioctyl sodium

sulfosuccinate (docusate sodium) and sodium lauryl sulfate, the Vaginal

Panel recommended the indication ``For the treatment of Trichomonas

vaginalis.'' For a combination product containing the ingredients

calcium propionate and sodium propionate, the Vaginal Panel recommended

the indication ``For the treatment of Candida albicans.'' For the

ingredient povidone-iodine, the Vaginal Panel recommended the

indication ``Clinically effective in a program of treatment for vaginal

moniliasis, T-vaginales vaginitis, and nonspecific vaginitis.''

In the preamble to the Vaginal Panel's report (48 FR 46694 at

46695), the agency disagreed with the Vaginal Panel's recommendations

regarding calcium propionate and sodium propionate. Based on previous

decisions made by the agency with respect to these ingredients under

the DESI program, the agency placed the professional labeling

indication recommended by the Vaginal Panel for calcium propionate and

sodium propionate in Category II. The agency reaffirms that

categorization in this document.

The agency also stated in the preamble to the Vaginal Panel's

report that OTC marketing of these ingredients for the relief of minor

vaginal irritations could not take place at that time because the

studies relied upon by the Panel were the same as those reviewed by the

agency and found to be inadequate under DESI. The agency invited

comment and data that would support the Panel's recommendations on the

safety and effectiveness of calcium propionate and sodium propionate as

ingredients in OTC vaginal drug products. No comments or new data were

submitted. Therefore, the agency is reaffirming its conclusions that

these ingredients, singly or in combination, may not be marketed in OTC

drug products with claims for vaginal use.

In recommending a professional labeling claim for docusate sodium

and sodium lauryl sulfate, the Panel relied upon one published study

(Ref. 1) to support its recommendation. The agency has evaluated this

study and finds that it is insufficient to determine the safety and

effectiveness of these ingredients for the treatment of Trichomonas

vaginalis. The study does not satisfy the criteria for an adequate and

well-controlled clinical study because it did not include a control

group. In addition, it was not designed to determine the effect of

these ingredients in treating Trichomonas but rather to determine the

effect of pH on the removal of secretions from the vagina. Therefore,

these ingredients, singly or in combination, may not be marketed in OTC

drug products with claims (including professional labeling claims) for

vaginal use.

Regarding the active ingredient povidone-iodine, the Panel (48 FR

46694 at 46705) stated that adequate data supported a claim of

effectiveness against vaginal yeast (candidiasis or moniliasis), T-

vaginales vaginitis and nonspecific vaginitis, but only when used in a

treatment regimen consisting of the diluted douche and the full

strength (10 percent) povidone-iodine products. Because the Vaginal

Panel (48 FR 46694 at 46700) believed that claims of therapeutic

benefit for treatment of specific vaginal infections must be restricted

to professional labeling, e.g., for the treatment of trichomoniasis or

moniliasis, labeling for the full strength (10 percent) product was not

included in the monograph. However, the agency has since concluded that

recurring vaginal yeast (Candida) infections can be safely treated OTC.

The agency is currently reviewing the data the Vaginal Panel considered

as well as a subsequent petition filed in support of various vaginal

claims and formulations for povidone-iodine (Ref. 4). The agency will

discuss the use of povidone-iodine for the treatment of vaginal yeast

(Candida) infections in a future Federal Register publication as part

of the rulemaking for OTC antifungal drug products.

Two clinical studies were cited in the data submission to the OTC

drug review to support the vaginitis claim (Refs. 2 and 3). The agency

has reviewed the two clinical studies and has concluded that they are

insufficient to demonstrate that povidone-iodine is effective in the

treatment of vaginitis. Neither study satisfies the criteria for

adequate and well-controlled studies because a control group was not

included. Therefore, they are insufficient to demonstrate the

effectiveness of povidone-iodine in the treatment of vaginitis.

References

(1) Fischer, R. R., ``Detergent Alkaline Douches,'' Pacific

Medicine and Surgery, 73:209-212, 1965.

(2) Shook, D. M., ``A Clinical Study of a Povidone-Iodine

Regimen for Resistant Vaginitis,'' Current Therapeutic Research,

5:256-263, 1963.

(3) Ratzan, J. J., ``Monilial and Trichomonal Vaginitis Topical

Treatment With Povidone-Iodine Preparations,'' California Medicine,

110:24-27, 1969.

(4) Comment No. CP, Docket No. 82N-0291, Dockets Management

Branch.

II. The Agency's Conclusions on OTC Vaginal Drug Products

FDA has considered the comments and other relevant data and

information available at this time and determined that specific claims

and ingredients for use in and around the vagina will be included in

other appropriate OTC drug rulemakings. Accordingly, the advance notice

of proposed rulemaking published in the Federal Register of October 13,

1983 (48 FR 46694), which would have added a new subpart B (Vaginal

Drug Products for Over-the-Counter Human Use) to proposed part 351

(Vaginal Contraceptive and Other Vaginal Drug Products for Over-the-

Counter Human Use) (proposed 21 CFR part 351), is hereby withdrawn,

effective February 3, 1994. As discussed above, claims that are

cosmetic claims only will not be considered in any OTC drug

rulemakings. Ingredients and drug claims related to use in and around

the vagina will be considered in other appropriate OTC drug

rulemakings. The agency has identified the following rulemakings as

those appropriate for consideration of ingredients and claims for

vaginal drug uses: (1) Antifungal drug products (docket No. 80N-0476),

(2) external analgesic drug products (docket No. 78N-0301), (3) skin

protectant drug products (docket No. 78N-0021), and (4) topical

antimicrobial drug products (Docket No. 75N-0183).

The agency emphasizes that it is withdrawing only the advance

notice of proposed rulemaking for these drug products and that this

withdrawal does not in any way denigrate the scientific content of the

report or negate the excellent work of the Vaginal Panel in its long

efforts to produce it. FDA believes that the information in the Vaginal

Panel's report will provide valuable guidance to the agency with

respect to ingredients and vaginal claims for other OTC drug

rulemakings. Further, this withdrawal of the advance notice of proposed

rulemaking does not affect the current marketing status of any of the

products that were considered in the Vaginal Panel's report. This

withdrawal notice is issued under authority of secs. 201, 501, 502,

503, 505, 510, 701 of the Federal Food, Drug, and Cosmetic Act (21

U.S.C. 321, 351, 352, 353, 355, 360, 371).

The agency has determined under 21 CFR 25.24(c)(6) 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.

Dated: December 10, 1993.

Michael R. Taylor,

Deputy Commissioner for Policy.

[FR Doc. 94-2263 Filed 2-2-94; 8:45 am]

BILLING CODE 4160-01-F