[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]]
_______________________________________________________________________
Part IX
Department of Health and Human Services
_______________________________________________________________________
Food and Drug Administration
_______________________________________________________________________
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
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
