[Federal Register Volume 60, Number 31 (Wednesday, February 15, 1995)]
[Rules and Regulations]
[Pages 8916-8920]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-3803]



      

[[Page 8915]]

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Part IX





Department of Health and Human Services





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Food and Drug Administration



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21 CFR Part 310



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

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

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-the-Counter 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.

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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 
<ls-thn-eq> 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