8916 Federal Register / Vol. 60, No. 31 / Wednesday, February 15, 1995 / Rules and Regulations

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 310

[Docket N0. 77N–334S]

RIN 0905–AA06

Topical Drug Products for Over-theCounter Human Use; Products for the

Prevention of Swimmer’s Ear and for

the Drying of Water-Clogged Ears;

Final Rule

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is issuing a final

rule establishing that any over-thecounter (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

§ 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 § 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 waterclogged 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

§ 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 §§ 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 § 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 § 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.

§§ 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
Federal Register / Vol. 60, No. 31 / Wednesday, February 15, 1995 / Rules and Regulations 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 ‘‘waterclogged 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
8918 Federal Register / Vol. 60, No. 31 / Wednesday, February 15, 1995 / Rules and Regulations

excess water in the ear could impair

hearing. Therefore, the drying of waterclogged 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

§ 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 § 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 waterclogged ears, neither anhydrous glycerin

nor isopropyl alcohol is included in a

monograph for this use. The agency’s
Federal Register / Vol. 60, No. 31 / Wednesday, February 15, 1995 / Rules and Regulations 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
8920 Federal Register / Vol. 60, No. 31 / Wednesday, February 15, 1995 / Rules and Regulations

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

§ 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 § 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:

§ 310.545 Drug products containing

certain active ingredients offered over-thecounter (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