Topical Drug Products for Over-the-Counter Human Use; Products for the Prevention of Swimmer's Ear and for the Drying of Water-Clogged Ears; Final Rule

SUMMARY: The Food and Drug Administration (FDA) is issuing a final rule

establishing that any over-the-counter (OTC) topical otic drug product

for the prevention of swimmer's ear or for the drying of water-clogged

ears is not generally recognized as safe and effective and is

misbranded. FDA is issuing this final rule after considering public

comments on the agency's proposed regulation, which was issued in the

form of a tentative final monograph, and all new data and information

on OTC topical otic drug products for these uses that have come to the

agency's attention. This final rule is part of the ongoing review of

OTC drug products conducted by FDA.

EFFECTIVE DATE: August 15, 1995.

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 December 16, 1977

(42 FR 63556), 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 topical otic drug products, together with the

recommendations of the Advisory Review Panel on OTC Topical Analgesic,

Antirheumatic, Otic, Burn, and Sunburn Prevention and Treatment Drug

Products (the Panel), which was the advisory review panel responsible

for evaluating data on the active ingredients in topical otic drug

products. Interested persons were invited to submit comments by March

16, 1978. Reply comments in response to comments filed in the initial

comment period could be submitted by April 14, 1978.

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

considered by the Panel, after deletion of a small amount of trade

secret information, were placed on public display in the Dockets

Management Branch (HFA-305), Food and Drug Administration, rm. 1-23,

12420 Parklawn Dr., Rockville, MD 20857.

In the December 16, 1977 advance notice of proposed rulemaking on

OTC topical otic drug products, the Panel discussed the treatment of

swimmer's ear (42 FR 63556 at 63565), but the Panel did not address the

prevention of swimmer's ear or the drying of water-clogged ears.

The agency's proposed regulation, in the form of a tentative final

monograph, for OTC topical otic drug products for the prevention of

swimmer's ear and for the drying of water-clogged ears was published in

the Federal Register of July 30, 1986 (51 FR 27366). Interested persons

were invited to file by September 29, 1986, written comments,

objections, or requests for oral hearing before the Commissioner of

Food and Drugs regarding the proposal. Interested persons were invited

to file comments on the agency's economic impact determination by

November 28, 1986. New data could have been submitted until July 30,

1987, and comments on the new data until September 30, 1987.

In the Federal Register of November 7, 1990 (55 FR 46914), the

agency published a final rule establishing that certain active

ingredients that had been under consideration in a number of OTC drug

rulemaking proceedings were not generally recognized as safe and

effective. That final rule was effective on May 7, 1991, and included

in Sec. 310.545(a)(15) (21 CFR 310.545(a)(15)) the active ingredient

acetic acid, which had been under consideration as part of this

rulemaking for OTC topical otic drug products for the prevention of

swimmer's ear and for the drying of water-clogged ears. This ingredient

was determined to be nonmonograph because no additional data had been

submitted following publication of the tentative final monograph to

determine whether acetic acid is generally recognized as safe and

effective as a topical otic drug products for the prevention of

swimmer's ear or for the drying of water-clogged ears. After that final

rule published, only two ingredients remained to be evaluated in this

rulemaking: Isopropyl alcohol and anhydrous glycerin. Final agency

action on all other OTC topical otic drug products for the prevention

of swimmer's ear and for the drying of water-clogged ears occurs with

the publication of this final rule.

In the tentative final monograph for OTC topical otic drug products

for the prevention of swimmer's ear and for the drying of water-clogged

ears (51 FR 27366), the agency did not propose any active ingredient as

generally recognized as safe and effective and not misbranded. However,

the agency proposed monograph labeling in the event that data were

submitted that resulted in the upgrading of any ingredient to monograph

status. In this final rule, however, no active ingredient has been

determined to be generally recognized as safe and effective for use in

OTC topical otic drug products for the prevention of swimmer's ear or

for the drying of water-clogged ears. Therefore, proposed

Secs. 344.3(c) through (f), 344.12, 344.14, 344.52, and 344.54 for OTC

topical otic drug products for the prevention of swimmer's ear and for

the drying of water-clogged ears are not being issued as a final

regulation.

This final rule declares OTC drug products containing active

ingredients for the prevention of swimmer's ear or for the drying of

water-clogged ears to be new drugs under section 201(p) of the Federal

Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 321(p)), for which an

application or abbreviated application (hereinafter called application)

approved under section 505 of the act (21 U.S.C. 355) and 21 CFR part

314 is required for marketing. In the absence of an approved

application, products containing these drugs for this use also would be

misbranded under section 502 of the act (21 U.S.C. 352). In appropriate

circumstances, a citizen petition to establish a monograph may be

submitted under Sec. 10.30 (21 CFR 10.30) in lieu of an application.

This final rule amends part 310 (21 CFR part 310) to include OTC

topical otic drug products containing active ingredients for the

prevention of swimmer's ear or for the drying of water-clogged ears by

adding new paragraph (a)(15)(ii) to Sec. 310.545 to include the

ingredients covered by this final rule, by redesignating the text of

paragraph (a)(15) as (a)(15)(i), by revising the heading of newly

redesignated paragraph (a)(15)(i), and by revising the heading of

paragraph (a)(15) to clarify that products for the drying of water-

clogged ears are also included. The inclusion of OTC topical otic drug

products for the prevention of swimmer's ear and for the drying of

water-clogged ears in part 310 is consistent with FDA's established

policy for regulations in which there are no monograph conditions.

(See, e.g. Secs. 310.510, 310.519, 310.525, 310.526, 310.532, 310.533,

310.534, and 310.536.) If, in the future, any ingredient is determined

to be generally recognized as safe and effective for use in an OTC

topical otic drug product for the [[Page 8917]] prevention of swimmer's

ear or for the drying of water-clogged ears, the agency will promulgate

an appropriate regulation at that time.

The OTC drug procedural regulations (21 CFR 330.10) now provide

that any testing necessary to resolve the safety or effectiveness

issues that formerly resulted in a Category III classification, and

submission to FDA of the results of that testing or any other data,

must be done during the OTC drug rulemaking process before the

establishment of a final monograph. Accordingly, FDA does not use the

terms ``Category I'' (generally recognized as safe and effective and

not misbranded), ``Category II'' (not generally recognized as safe and

effective or misbranded), and ``Category III'' (available data are

insufficient to classify as safe and effective, and further testing is

required) at the final monograph stage. In place of Category I, the

term ``monograph conditions'' is used; in place of Categories II or

III, the term ``nonmonograph conditions'' is used.

In the tentative final monograph for OTC topical otic drug products

(51 FR 27366 at 27367), the agency advised that the conditions under

which the drug products are subject to the monograph would be generally

recognized as safe and effective and not misbranded would be effective

12 months after the date of publication of the final monograph in the

Federal Register. Although data and information were submitted in

response to the proposed rule, they were not sufficient to support

monograph conditions, and no monograph is being established at this

time. Therefore, topical otic drug products that are subject to this

rule are not generally recognized as safe and effective and are

misbranded (nonmonograph conditions). Because no OTC drug monograph is

being established for this class of drug products, the agency is

adopting its standard 6-month effective date for the nonmonograph

conditions in this final rule. Therefore, on or after August 15, 1995,

no OTC drug products that are subject to this final rule may be

initially introduced or initially delivered for introduction into

interstate commerce unless they are the subject of an approved

application.

In response to the proposed rule on OTC topical otic drug products

for the prevention of swimmer's ear and for the drying of water-clogged

ears, two drug manufacturers submitted comments on isopropyl alcohol

and anhydrous glycerin, and one physician submitted a comment on

isopropyl alcohol and acetic acid. Copies of the comments received are

on public display in the Dockets Management Branch (address above).

Additional information that has come to the agency's attention since

publication of the proposed rule is also on public display in the

Dockets Management Branch.

I. The Agency's Conclusions on the Comments

A. General Comments

1. One comment contended that products for the treatment of

``water-clogged ears'' are not drugs within the meaning of section

201(g) of the act (21 U.S.C. 321(g)) and, thus, are not the proper

subject of an OTC drug monograph. The comment stated that section

201(g)(1) of the act defines a drug, in part, as ``* * * (B) articles

intended for use in the diagnosis, cure, mitigation, treatment, or

prevention of disease in man or other animals; and (C) articles (other

than food) intended to affect the structure or any function of the body

of man or other animals * * *.'' The comment argued that these products

are not intended for use in connection with ``any disease,'' do not

affect the structure or any function of the body, and are not meant to

have any effect on the body. The comment mentioned that FDA had

previously stated that ``water-clogged ears is not a recognized

clinical entity or a term found in textbooks,'' (Refs. 1 and 2) and

thus, in FDA's view, the condition ``water-clogged ears'' is not a

disease.

The comment added that if FDA concluded that such products are

intended for use in connection with a ``disease'' or affect the

structure or a function of the body, then the products should be

regulated as a device rather than as a drug. The comment stated that

section 201(h) of the act (21 U.S.C 321(h)) states that a device ``does

not achieve its primary intended purposes through chemical action

within or on the body * * * and * * * is not dependent upon being

metabolized for the achievement of its primary intended purposes.'' The

comment contended that products that function by drying excess water

work by a purely physical process and that the product is not

metabolized.

Despite the comment's arguments, the agency considers products

``for the drying of water in the ears'' or ``to help relieve the

discomfort of water-clogged ears by drying excess water'' to be drugs

and not devices. All drugs do not need to be metabolized. Some work by

a purely physical process, such as a skin protectant that forms a

physical barrier.

The act defines a device, in section 201(h), in part, as an

instrument, apparatus, implement, machine, contrivance, implant, in

vitro reagent, or other similar or related article, including any

component, part, or accessory, which is: (1) Recognized in the official

National Formulary, or the United States Pharmacopeia, or any

supplement to them, (2) intended for use in the diagnosis of disease or

other conditions, or in the cure, mitigation, treatment, or prevention

of disease, in man or other animals, or (3) intended to affect the

structure or any function of the body of man or other animals, and

which does not achieve its primary intended purposes through chemical

action within or on the body of man or other animals and which is not

dependent upon being metabolized for the achievement of its primary

intended purposes. The agency has determined that these products do not

meet the definition of a device because they are not an instrument,

apparatus, implement, machine, contrivance, implant, in vitro reagent,

or other similar or related article.

As discussed in the Panel's report (42 FR 63556 at 63565), external

otitis, an infection of the skin lining the external auditory canal, is

one of the most common diseases of the ear. One type of external otitis

is called ``diffuse external otitis'' and is commonly known as

``swimmer's ear.'' It occurs with greater frequency during hot, humid

weather and has been reported to occur in divers and swimmers.

``Swimmer's ear'' is apparently due to excessive moisture in the

external auditory meatus, which may be the result of various causes.

The external auditory canal is a cul-de-sac, well suited for the

collection of moisture, thus providing a basis for infection.

Disruption of the skin lining of the external auditory canal by the

action of the accumulated moisture, or by the use of instruments to

clear the ear canal of water after bathing or swimming, may cause

maceration, fissuring, or laceration of the skin lining and provide a

favorable environment for the growth of bacteria or fungi. Although the

action of products that dry water in the ear is limited to removal of

the excess water, if this condition is left untreated, it could result

in ``swimmer's ear.''

In the tentative final monograph (51 FR 27366 at 27367), the agency

stated that it recognized a population that is prone to develop

swimmer's ear and that the availability of OTC drug products to prevent

the occurrence of this condition would benefit the consumer. Products

that dry water in the ear may prevent the occurrence of ``swimmer's

ear'' and, thus, help prevent disease. As discussed in the tentative

final monograph (51 FR 27366 at 27370), the agency also believes that

[[Page 8918]] excess water in the ear could impair hearing. Therefore,

the drying of water-clogged ears may affect the function of the ear by

reducing a loss of hearing in some individuals. Accordingly, the agency

concludes that products that dry water in the ears are drugs under

section 201(g) of the act.

References

(1) Letter from W. E. Gilbertson, FDA, to H. W. Gordon, Commerce

Drug Co., Inc., coded LET006, Docket No. 77N-0334, Dockets

Management Branch.

(2) Letter from W. E. Gilbertson, FDA, to H. W. Gordon, Commerce

Drug Co., Inc., coded LET010, Docket No. 77N-0334, Dockets

Management Branch.

2. One comment requested that products for drying water-clogged

ears be allowed to make the claim ``helps relieve swimmer's ear.'' The

comment stated that the agency's proposed definition of ``swimmer's

ear'' in Sec. 344.3(e) (51 FR 27366 at 27373) was too restrictive

because it included a demonstration of effectiveness against external

otitis in a susceptible target population. The comment mentioned that

consumers have long used the term ``swimmer's ear'' to refer to the

retention of excess water in the ears after swimming, showering, or

bathing. The comment argued that a demonstration of efficacy against

external otitis should not be a prerequisite for a claim relating to

``swimmer's ear.''

The agency disagrees with the comment. The Panel (42 FR 63556 at

63565) defined swimmer's ear as a ``diffuse external otitis,'' an

infection of the skin lining the external auditory canal. Likewise,

other medical experts (Ref. 1) define swimmer's ear as external otitis

associate with swimming. Clinical symptoms include an itchy or painful,

discharging ear, and a tender edematous canal filled with debris.

Pseudomonas aeruginosa is the predominant bacterial pathogen in cases

of external otitis. Successful treatment of the infection can require a

combination of topical therapies, including antibiotics, steroids,

drying agents, and acetic acid. If not successfully treated, swimmer's

ear may lead to malignant external otitis and mastoiditis. For these

reasons, the agency considers diagnosis and treatment of this infection

by a physician to be necessary.

The comment did not submit any data to demonstrate that ear water-

drying aid products alone ``help relieve swimmer's ear.'' Data showing

effectiveness of an ear water-drying aid product as a single agent

against external otitis would be a prerequisite for a claim relating to

``swimmer's ear.'' The agency concludes that the existing data are

inadequate to support a relief of swimmer's ear claim for any ear

water-drying aid drug product.

Reference

(1) Mandell, G. L., G. Douglas, and J. E. Bennett, ``Principles

and Practice of Infectious Diseases,'' 3d ed., Churchill

Livingstone, New York, pp. 1680-1681, 1990.

3. One comment requested that the proposed indications in

Sec. 344.52(b) for products for drying water-clogged ears be expanded

to permit mention of the source of the water in the ears causing the

problem. The comment suggested adding the following words to the

indications: (``caused by'' or ``resulting from'') ``swimming,

showering, or bathing.''

The agency would have no problems in allowing the indications to

mention the source of the water. However, this would not be required

information because the proposed indications adequately describe the

use of the product. The agency would allow the source of the water to

appear as optional additional information that could appear at the

manufacturer's choice. At this time, indications for these products

will not appear in the final rule because no active ingredients are

included in a monograph for this class of OTC drug products. Should a

monograph be proposed in the future, the optional expanded indications

will be considered.

B. Comments on Isopropyl Alcohol and Anhydrous Glycerin

4. One comment submitted a study (Ref. 1) to support the

effectiveness of 5 percent anhydrous glycerin in 95 percent isopropyl

alcohol for the drying of water-clogged ears. The comment stated that

if FDA determines that this product is a drug, it should be classified

as Category I.

The agency has reviewed the study and determined that the data are

insufficient to demonstrate the effectiveness of 5 percent anhydrous

glycerin in 95 percent isopropyl alcohol for the drying of water-

clogged ears. This study involved 27 male or female volunteers, between

18 and 65 years of age, with a history of water-clogged ears. The

subjects were in generally good health with ears free of obstructions

and tympanic membranes free of any perforations. The objective of the

study was to determine the effectiveness of 5 percent anhydrous

glycerin in 95 percent isopropyl alcohol placed in the external

auditory canal to speed up the evaporation of water. Each subject was

placed in the supine position, and the ear was inspected with an

operating microscope. The ear to be tested was then filled with

lukewarm water. Each subject was permitted to tilt his/her head to

allow the water to run freely out of the ear onto absorbent cotton.

Only those subjects with water remaining in their ears were selected.

The presence of water was recorded on tape by means of an operating

microscope and its television camera. Five drops of product or water,

as a placebo, were then randomly instilled into the ear. The samples

were coded to maintain a double-blind so that both the investigator and

subjects were unaware of the material instilled. After 5 minutes, the

ear was inspected under the operating microscope and the presence or

absence of water was determined. The quantity of water present after

treatment was recorded as ``more,'' ``same,'' ``less,'' or ``none.''

The findings were recorded on tape and the subject record form.

Because participants were selected based on a history of some

problem with retaining water in the ears after exposure, it is the

agency's view that it is inappropriate to use a water-only placebo in a

study of the indication for relief of ``water-clogged ears.'' In such

situations, the water-only group would be expected to do worse than a

group left untreated after water exposure. The agency is also concerned

that the method used in the study did not specify how the head was

tilted nor did it specify the time allowed for the water to run freely

out of the ear onto the absorbent cotton. The position of the head and

the length of time allowed for the water removal from the ear should

have been specified.

The agency does not consider a study population of 27 subjects

adequate to demonstrate that the results are statistically significant.

Based on its statistical evaluation of the results, the comment

reported that the product was effective in 22 out of 25 subjects' ears

(88 percent) and that the placebo was effective in 3 out of 24

subjects' ears (12 percent), a highly significant result (Chi Square

99.9 percent). However, the agency finds that a Yates

correction of Chi Square should have been used for this small cell size

study. A reanalysis using this correction was never provided.

While the study provides some supportive information on the

product's drying effect, at least one additional well-designed

confirmatory study with an adequate number of subjects is needed.

Because the submitted data are inadequate to establish effectiveness

for the drying of symptoms of water-clogged ears, neither anhydrous

glycerin nor isopropyl alcohol is included in a monograph for this use.

The agency's [[Page 8919]] detailed comments and evaluation of the

above data are on file in the Dockets Management Branch (Ref. 2).

The agency considers this product to be a drug. (See discussion in

section I.B., comment 5.) The agency has been informed that the comment

plans to conduct another study to establish the effectiveness of this

product for the drying of water-clogged ears (Refs. 3 and 4). When the

study is completed, the comment should submit the data in the form of a

petition to establish a monograph for this type of OTC drug product.

References

(1) Brookler, K. H., ``Evaluation of Auro-Dri in the Relief for

Water-Clogged Ears,'' Comment No. C2, Docket No. 77N-334S, Dockets

Management Branch.

(2) Letter from W. E. Gilbertson, FDA, to H. W. Gordon, Del

Laboratories, coded LET5, Docket No. 77N-334S, Dockets Management

Branch.

(3) Comment No. C5, Docket No. 77N-334S, Dockets Management

Branch.

(4) Memorandum of meeting between representatives of Del

Laboratories, Inc., and FDA, coded MM1, Docket No. 77N-334S.

5. One comment discussed the status of glycerin in a product

containing 5 percent anhydrous glycerin in 95 percent isopropyl

alcohol. The comment contended that glycerin was not an active

ingredient, but that glycerin was the vehicle. The comment stated that

the product did not make any claims for glycerin as an active

ingredient and thus no further testing for the glycerin in this product

was necessary. The comment stated that glycerin was miscible with both

water and alcohol (Ref. 1) and, thus, glycerin was particularly

appropriate for use as a vehicle in this product.

The comment pointed out that the agency had previously stated (Ref.

2):

In order to meet the requirements for a combination product,

each ingredient must be tested alone and also in combination to show

effectiveness for the proposed claims. However, if glycerin

functions only as a vehicle (and the need for it as a vehicle is

shown) and no claims are made for it as an active ingredient,

additional testing would not be required for this ingredient.

The comment added that the Panel stated in its report on OTC topical

otic drug products (42 FR 63556 at 63562) that ``glycerin is used in

topical otic products * * * as a vehicle because of its solvent

properties. * * * Its viscosity makes it useful as an ingredient in

both liquid and ointment forms of medication. * * * Glycerin is widely

accepted as a vehicle of choice in otic products.''

The agency does not have sufficient information demonstrating that

anhydrous glycerin functions only as a vehicle in this product. The

anhydrous glycerin could have an active role in the product. One text

states that anhydrous glycerin alone, or mixed with vinegar, will help

to remove water from the ear (Ref. 3). The comment did not provide any

data to show that at the 5 percent concentration present the anhydrous

glycerin does not contribute to the effect of the product. In order to

show that glycerin does not have an active role in the product, it

needs to be shown that the product with the glycerin is not superior to

95 percent isopropyl alcohol used alone. If the combination is

superior, this would show that the anhydrous glycerin contributes to

the product's effectiveness. The agency believes that a four-arm study

(combination, 95 percent isopropyl alcohol, anhydrous glycerin alone,

and placebo, which would be no treatment) should be conducted to

clarify the role of the glycerin in the product.

In addition, if the glycerin were found to act only as a vehicle,

then the product would have to be labeled accordingly. The product

could not continue to be labeled as 5 percent anhydrous glycerin in 95

percent isopropyl alcohol.

References

(1) ``The Pharmacological Basis of Therapeutics,'' 6th ed.,

edited by L. S. Goodman, and A. G. Gilman, The McMillan Co., New

York, p. 951, 1980.

(2) Letter from W. E. Gilbertson, FDA, to H. W. Gordon, Commerce

Drug Co., Inc., coded LET10, Docket No. 77N-0334, Dockets Management

Branch.

(3) ``Handbook of Nonprescription Drugs,'' 10th ed., American

Pharmaceutical Association, Washington, p. 400, 1993.

C. Comments on the Isopropyl Alcohol and Acetic Acid

6. One comment requested that a combination product containing 95

percent isopropyl alcohol and 3 percent acetic acid be included in the

final monograph with a claim for the prevention of swimmer's ear. The

comment urged the agency to consider this combination because isopropyl

alcohol with anhydrous glycerin was proposed as category III for drying

of water in the ears (51 FR 27366 at 27370) and 2 percent acetic acid

in distilled water was category III for prevention of swimmer's ear (51

FR 27367). The comment stated that preliminary data from a study

suggested that this product may be statistically significant in

diminishing the frequency of otitis externa in children during the

summer months. The comment concluded that a product containing 95

percent isopropyl alcohol and 3 percent acetic acid was effective in

drying of excess moisture in the ears as well as re-establishing the

acid mantle in the ear canals.

As the comment noted, in the tentative final monograph, the agency

placed several products in category III: (1) 2 percent acetic acid in

distilled water or propylene glycol and the combination of 5 percent

anhydrous glycerin and 95 percent isopropyl alcohol for the prevention

of swimmer's ear, and (2) the combination of 5 percent anhydrous

glycerin and 95 percent isopropyl alcohol for the drying of water in

the ears or for the relief of the discomfort of water-clogged ears by

drying excess water.

The comment did not submit any data on this combination, nor was

this combination considered by the Panel in its report or the agency in

the tentative final monograph. More data were needed on all of these

products. Likewise, adequate data to demonstrate the safety and

effectiveness of the comment's product are needed. Because no data were

submitted to establish safety and effectiveness, the combination of 95

percent isopropyl alcohol and 3 percent acetic acid for the prevention

of swimmer's ear is not being included in a monograph.

II. The Agency's Final Conclusions on OTC Topical Otic Drug

Products for the Prevention of Swimmer's Ear and for the Drying of

Water-Clogged Ears

At this time, there is a lack of data from adequate and well-

controlled studies to establish that acetic acid, isopropyl alcohol,

anhydrous glycerin, or any other ingredients are safe and effective for

use as a topical otic drug product for the prevention of swimmer's or

for the drying of water-clogged ears.

Therefore, any ingredient that is labeled, represented, or promoted

for OTC use as a topical otic drug product for the prevention of

swimmer's ear or for the drying of water-clogged ears is considered

nonmonograph and misbranded under section 502 of the act and is a new

drug under section 201(p) of the act for which an approved application

under section 505 of the act and part 314 of the regulations (21 CFR

part 314) is required for marketing. In appropriate circumstances, a

citizen petition to establish a monograph may be submitted under 21 CFR

10.30 in lieu of an application. Any such OTC drug product initially

introduced or initially delivered for introduction into interstate

commerce after the effective date of this final rule that is not in

compliance with the regulation is subject to regulatory action.

In the Federal Register of November 7, 1990 (55 FR 46914), the

agency published a final rule in 21 CFR part [[Page 8920]] 310,

establishing that certain ingredients under consideration in a number

of OTC drug rulemaking proceedings were not generally recognized as

safe and effective. That final rule was effective on May 7, 1991, and

included in Sec. 310.545(a)(15) the ingredient acetic acid that had

been previously considered under this rulemaking for use as a topical

otic drug product for the prevention of swimmer's ear and for the

drying of water-clogged ears. The agency is revising

Sec. 310.545(a)(15) to clarify that products for the drying of water-

clogged ears are also included in the regulation and to add new

paragraph (a)(15)(ii) to include the ingredients covered by this final

rule.

III. Analysis of Impacts

No comments were received in response to the agency's request for

specific comment on the economic impact of this rulemaking (51 FR 27366

at 27371). FDA has examined the impacts of the final rule under

Executive Order 12866 and the Regulatory Flexibility Act (Pub. L. 96-

354). 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). The agency

believes that this final rule is consistent with the regulatory

philosophy and principles identified in the Executive Order. In

addition, the final rule is not a significant regulatory action as

defined by the Executive Order and, thus, is not subject to review

under the Executive Order.

The Regulatory Flexibility Act requires agencies to analyze

regulatory options that would minimize any significant impact of a rule

on small entities. This particular rulemaking for OTC topical otic drug

products for the prevention of swimmer's ear and for the drying of

water-clogged ears is not expected to pose such an impact on small

businesses. As noted above, the ingredient acetic acid has already been

removed from OTC topical otic drug products for the prevention of

swimmer's ear and for the drying of water-clogged ears. The agency is

only aware of several OTC topical otic drug products containing

isopropyl alcohol and anhydrous glycerin labeled for these uses.

Accordingly, based on the number of affected products, the agency

certifies that this final rule will not have a significant economic

impact on a substantial number of small entities. Therefore, under the

Regulatory Flexibility Act, no further analysis is required.

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.

List of Subjects in 21 CFR Part 310

Administrative practice and procedure, Drugs, Labeling, Medical

devices, Reporting and recordkeeping requirements.

Therefore, under the Federal Food, Drug, and Cosmetic Act and under

authority delegated to the Commissioner of Food and Drugs, 21 CFR part

310 is amended as follows:

PART 310--NEW DRUGS

1. The authority citation for 21 CFR part 310 continues to read as

follows:

Authority: Secs. 201, 301, 501, 502, 503, 505, 506, 507, 512-

516, 520, 601(a), 701, 704, 705, 721 of the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 357,

360b-360f, 360j, 361(a), 371, 374, 375, 379e; secs. 215, 301,

302(a), 351, 354-360F of the Public Health Service Act (42 U.S.C.

216, 241, 242(a), 262, 263b-263n).

2. Section 310.545 is amended by revising paragraphs (a)(15) and

(d)(1) and by adding new paragraph (d)(18) to read as follows:

Sec. 310.545 Drug products containing certain active ingredients

offered over-the-counter (OTC) for certain uses.

(a) * * *

(15) Topical otic drug products for the prevention of swimmer's ear

and for the drying of water-clogged ears--(i) Approved as of May 7,

1991.

Acetic acid

(ii) Approved as of August 15, 1995.

Glycerin and anhydrous glycerin

Isopropyl alcohol

* * * * *

(d) * * *

(1) May 7, 1991, for products subject to paragraphs (a)(1) through

(a)(2)(i), (a)(3) through (a)(4), (a)(6)(i)(A), (a)(6)(ii)(A), (a)(7)

(except as covered by paragraph (d)(3) of this section), (a)(8)(i),

(a)(9) through (a)(10)(iii), (a)(12)(i) through (a)(12)(iv), and

(a)(14) through (a)(18)(i) of this section.

* * * * *

(18) August 15, 1995, for products subject to paragraph (a)(15)(ii)

of this section.

* * * * *

Dated: January 31, 1995.

William K. Hubbard,

Interim Deputy Commissioner for Policy.

[FR Doc. 95-3803 Filed 2-14-95; 8:45 am]

BILLING CODE 4160-01-F