[Federal Register Volume 65, Number 155 (Thursday, August 10, 2000)]
[Rules and Regulations]
[Pages 48902-48905]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-19992]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 201, 310, and 344

[Docket No. 77N-334S]
RIN 091O-AA01


Topical Otic Drug Products for Over-the-Counter Human Use; 
Products for Drying Water-Clogged Ears; Amendment of Monograph; Lift of 
Partial Stay of Effective Date

AGENCY: Food and Drug Administration, HHS.

ACTION:  Final rule; lift of partial stay of effective date.

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SUMMARY: The Food and Drug Administration (FDA) is issuing a final rule 
amending the monograph for over-the-counter (OTC) topical otic drug 
products (the regulation that establishes conditions under which these 
drug products are generally recognized as safe and effective and not 
misbranded). The amendment adds conditions for marketing topical otic 
drug products for drying water-clogged ears and includes labeling in 
the new OTC drug format. The agency is amending its final regulations 
for OTC drug labeling requirements to include the new flammability 
warning for topical otic drug products for drying water-clogged ears. 
The agency is also lifting a partial stay of the effective date of 
certain provisions of the regulations for topical otic drug products 
for the drying of water clogged ears. This final rule is part of the 
ongoing review of OTC drug products conducted by FDA.

DATES:   
    Effective Date: This rule is effective May 17, 2002. The stay of 
Sec. 310.545 (a)(15)(ii) for topical otic drug products for the drying 
of water-clogged ears that published at 60 FR 42436 on August 16, 1995, 
and effective June 22, 1995, is lifted effective September 11, 2000.
    Compliance Date: The compliance date for products with annual sales 
less that $25,000 is May 17, 2003. The compliance date for all other 
OTC drug products is May 17, 2002.

FOR FURTHER INFORMATION CONTACT:  Gerald M. Rachanow, Center for Drug 
Evaluation and Research (HFD-560), Food and Drug Administration, 5600

[[Page 48903]]

Fishers Lane, Rockville, MD 20857, 301-827-2307.

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of July 9, 1982 (47 FR 30012), the agency 
published a tentative final monograph for OTC topical otic drug 
products used as earwax removal aids. Subsequently, in the Federal 
Register of July 30, 1986 (51 FR 27366), the agency proposed to amend 
this tentative final monograph to consider OTC topical otic drug 
products for the prevention of swimmer's ear and for the drying of 
water-clogged ears. At that time, no topical otic drug products for 
these conditions were proposed as generally recognized as safe and 
effective and not misbranded. The agency, however, did propose Category 
I (monograph) labeling for such products in case data were submitted 
that resulted in upgrading any ingredient(s) to monograph status in a 
final rule.
    In the Federal Register of August 8, 1986 (51 FR 28656), the agency 
issued a final rule establishing part 344 (21 CFR part 344) for topical 
otic drug products for OTC human use. The monograph included one active 
ingredient for use as an earwax removal aid.
    In the Federal Register of November 7, 1990 (55 FR 46914), 
(hereinafter referred to as the 1990 final rule) 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. The 1990 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. After the 1990 final rule published, only two 
ingredients remained to be evaluated in this rulemaking: Isopropyl 
alcohol and anhydrous glycerin.
    In the Federal Register of February 15, 1995 (60 FR 8916), the 
agency issued a final rule establishing that OTC topical otic drug 
products for prevention of swimmer's ear or for drying water-clogged 
ears were not generally recognized as safe and effective for OTC use 
and were new drugs under section 201(p) of the Federal Food, Drug, and 
Cosmetic Act (the act) (21 U.S.C. 321(p)). The agency listed the 
ingredients considered in the rulemaking (i.e., glycerin, anhydrous 
glycerin, and isopropyl alcohol) in Sec. 310.545(a)(15)(ii), with an 
effective date of August 15, 1995, after which products containing 
these ingredients for these uses could no longer be initially 
introduced or initially delivered for introduction into interstate 
commerce. Acetic acid, which had been listed solely in Sec. 310.545, 
was now listed in Sec. 310.545(a)(15)(i), with the same effective date 
of May 7, 1991. This final rule did not affect the conclusion reached 
in the 1990 and 1995 final rules that acetic acid was not generally 
recognized as safe and effective for the prevention of swimmer's ear or 
for the drying of water-clogged ears. The phrase ``approved as of May 
7, 1991'' in Sec. 310.545(a)(15)(i) indicates when this conclusion 
became effective for acetic acid.
    Subsequently, a drug manufacturer submitted new data (Ref. 1) to 
support the use of a product containing 95 percent isopropyl alcohol in 
a 5 percent anhydrous glycerin base for drying water-clogged ears. The 
agency determined that the data supported the use of this product for 
drying water-clogged ears (Ref. 2). Accordingly, in the Federal 
Register of August 16, 1995 (60 FR 42435), the agency issued a partial 
stay of the August 15, 1995, effective date for Sec. 310.545(a)(15)(ii) 
for products containing 95 percent isopropyl alcohol in a 5 percent 
anhydrous glycerin base used for the drying of water-clogged ears. This 
partial stay applied only to products with these ingredients for drying 
water-clogged ears. The new data and the stay did not involve other 
ingredients, such as acetic acid, and did not pertain to the prevention 
of swimmer's ear.
    The agency is lifting the partial stay of the August 15, 1995, 
effective date of certain provisions of the regulations for topical 
otic drug products for the drying of water clogged ears. The August 15, 
1995, effective date for Sec. 310.545(a)(15)(ii) remains in effect for 
the listed ingredients when used in topical otic drug products for the 
prevention of swimmer's ear.
    In the Federal Register of August 17, 1999 (64 FR 44671), the 
agency published a proposed amendment of the monograph for OTC topical 
otic drug products to add conditions for marketing products with 
isopropyl alcohol and anhydrous glycerin for drying water-clogged ears. 
The proposal contained labeling in the new OTC drug format in 
Sec. 201.66 (21 CFR 201.66). Concurrently, the agency proposed to 
remove the drying of water-clogged ears from one part of 
Sec. 310.545(a)(15) by revising the headings of paragraphs (a)(15), 
(a)(15)(i), and (a)(15)(ii).
    Interested persons were invited to submit comments on the proposal 
and on the agency's economic impact determination by November 15, 1999. 
The agency did not receive any comments in response to the proposal.

II. The Agency's Final Conclusions

    The agency concludes that a product consisting of isopropyl alcohol 
95 percent in an anhydrous glycerin 5 percent base is generally 
recognized as safe and effective for OTC use for the drying of water-
clogged ears and that such a product is not misbranded when it contains 
the labeling in new Sec. 344.52 and is consistent with Sec. 330.1 (21 
CFR 330.1). No other product or ingredient has been found to be 
generally recognized as safe and effective for this use.
    Existing part 344 currently includes only topical otic drug 
products used as earwax removal aids. The current headings for 
Secs. 344.10 and 344.50 refer to a topical otic active ingredient and 
labeling of topical otic drug products, respectively. Accordingly, 
Secs. 344.10 and 344.50 are changed to ``Earwax removal aid active 
ingredient'' and ``Labeling of earwax removal aid drug products,'' 
respectively. The agency is including new Secs. 344.12 and 344.52 as 
``Ear drying aid active ingredient,'' and ``Labeling of ear drying aid 
drug products,'' respectively. The agency is deleting Sec. 344.50(e), 
which refers to substitution of the word ``physician'' for the word 
``doctor,'' because this is now included in Sec. 330.1(i)(23). The 
agency is listing the flammability warning in Sec. 344.52(c) in 
Sec. 201.66(c)(5)(ii)(C).

III. Analysis of Impacts

    FDA has examined the impacts of the final rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612) (as 
amended by subtitle D of the Small Business Regulatory Fairness Act of 
1996 (Public Law 104-121)), and the Unfunded Mandates Reform Act of 
1995 (Public Law 104-4.). 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). Under the Regulatory Flexibility Act, if a rule has a 
significant economic impact on a substantial number of small entities, 
an agency must analyze regulatory options that would minimize any 
significant impact of the rule on small entities. Title II of the 
Unfunded Mandates Reform Act requires that agencies

[[Page 48904]]

prepare a written statement and economic analysis before proposing any 
rule that may result in an expenditure in any one year by State, local, 
and tribal governments, in the aggregate, or by the private sector, of 
$100 million (adjusted annually for inflation).
    The agency concludes that this final rule is consistent with the 
principles set out in the Executive Order and in these two statutes. 
The final rule is not a significant regulatory action as defined by the 
Executive Order and so is not subject to review under the Executive 
Order. FDA has determined that the final rule does not have a 
significant economic impact on a substantial number of small entities. 
Further, since this final rule makes no mandates on government entities 
and will result in expenditures less than $100 million in any one year, 
FDA need not prepare additional analyses under the Unfunded Mandates 
Reform Act.
    The purpose of this final rule is to establish conditions for OTC 
drug products containing alcohol and glycerin used to dry water-clogged 
ears. This final rule amends the final monograph for OTC topical otic 
drug products and will require some product relabeling. The agency's 
Drug Listing System identifies only one manufacturer/marketer of one 
stockkeeping unit (SKU) (individual product, package, and size) of OTC 
topical otic drug products with these ingredients for drying water-
clogged ears. There may be other manufacturers/marketers not identified 
in sources FDA reviewed, but the agency believes there are a limited 
number.
    The agency believes that relabeling costs of the type required by 
this final rule generally average about $2,000 to $3,000 per SKU. 
Assuming there could be as many as five affected OTC SKU's in the 
marketplace, total one-time costs of relabeling would be $10,000 to 
$15,000. The agency believes that the actual cost could be lower for 
several reasons.
    First, the labeling in the monograph is in the new OTC drug 
labeling format found in Sec. 201.66. Therefore, manufacturers will not 
incur any expenses determining how to state the product's labeling. 
Second, manufacturers will be able to incorporate product labeling 
changes required by the final monograph and the new general OTC drug 
labeling requirements at one time. Thus, the relabeling costs resulting 
from two different but related final rules will be individually reduced 
by implementing both required changes at the same time, thereby 
reducing the labeling cost of this final rule.
    Third, the one identified manufacturer/marketer is a small entity 
using the U.S. Small Business Administration designations for this 
industry (750 employees). The agency believes that any other 
unidentified manufacturer of these products is probably also a small 
entity. Small entities tend to use simpler and less expensive labeling. 
In addition, based on the limited number of SKU's (usually only one) 
each manufacturer has to relabel, the cost for each manufacturer should 
be minimal. Finally, the final rule will not require any new reporting 
and recordkeeping activities. Thus, no additional professional skills 
are needed.
    The agency rejected an exemption for small entities because the new 
labeling information is also needed by consumers who purchase products 
marketed by those entities. However, a longer effective date until May 
17, 2003, is being provided for products with annual sales less than 
$25,000.
    For the reasons stated above and under the Regulatory Flexibility 
Act (5 U.S.C. 605(b)), the Commissioner certifies that this rule will 
not have a significant economic impact on a substantial number of small 
entities.

IV. Paperwork Reduction Act of 1995

    FDA concludes that the labeling requirements in this final rule are 
not subject to review by the Office of Management and Budget because 
they do not constitute a ``collection of information'' under the 
Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq.). Rather, the 
labeling requirements are a ``public disclosure of information 
originally supplied by the Federal Government to the recipient for the 
purpose of disclosure to the public'' (5 CFR 1320.3(c)(2)).

V. Environmental Impact

    The agency has determined under 21 CFR 25.31(a) 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.

VI. References

    The following references are on display in the Dockets Management 
Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 
1061, Rockville, MD 20852, and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.
    1. Comment No. CP1, Docket No. 77N-334S, Dockets Management Branch.
    2. Letter from W. E. Gilbertson, FDA, to N. Buc, Buc Levitt & 
Beardsley, attorneys for Del Pharmaceuticals, Inc., coded LET13, Docket 
No. 77N-334S, Dockets Management Branch.

List of Subjects

21 CFR Part 201

    Drugs, Labeling, Reporting and recordkeeping requirements.

21 CFR Part 310

    Administrative practice and procedure, Drugs, Labeling, Medical 
devices, Reporting and recordkeeping requirements.

21 CFR Part 344

    Labeling, Over-the-counter drugs.


    Therefore, under secs. 201-907 of the Federal Food, Drug, and 
Cosmetic Act and under authority delegated to the Commissioner of Food 
and Drugs, the partial stay for Sec. 310.545(a)(15)(ii) for topical 
otic drug products for the drying of water-clogged ears that published 
in the Federal Register of August 16, 1995 (60 FR 42436), is lifted 
effective September 11, 2000, and 21 CFR parts 201, 310, and 344 are 
amended as follows:

PART 201--LABELING

    1. The authority citation for 21 CFR part 201 continues to read as 
follows:

    Authority:  21 U.S.C. 321, 331, 351, 352, 353, 355, 358, 360, 
360b, 360gg-360ss, 371, 374, 379e; 42 U.S.C. 216, 241, 262, 264.


    2. Section 201.66 is amended by revising paragraph (c)(5)(ii)(C) to 
read as follows:


Sec. 201.66  Format and content requirements for over-the-counter (OTC) 
drug product labeling.

* * * * *
    (c) * * *
    (5) * * *
    (ii) * * *
    (C) Flammability warning, with appropriate flammability signal 
word(s) (e.g., Secs. 341.74(c)(5)(iii), 344.52(c), 358.150(c), and 
358.550(c) of this chapter). This warning shall follow a subheading 
containing the appropriate flammability signal word(s) described in an 
applicable OTC drug monograph or approved drug application.
* * * * *

PART 310--NEW DRUGS

    3. The authority citation for 21 CFR part 310 continues to read as 
follows:


[[Page 48905]]


    Authority:  21 U.S.C. 321, 331, 351, 352, 353, 355, 360b-360f, 
360j, 361(a), 371, 374, 375, 379e; 42 U.S.C. 216, 241, 242(a), 262, 
263b-263n.


    4. Section 310.545 is amended by revising the headings of 
paragraphs (a)(15) and (a)(15)(i), and by revising paragraph 
(a)(15)(ii) 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--(i) For the prevention of 
swimmer's ear and for the drying of water-clogged ears, approved as of 
May 7, 1991.
* * * * *
    (ii) For the prevention of swimmer's ear, approved as of August 15, 
1995.
    Glycerin and anhydrous glycerin
    Isopropyl alcohol
* * * * *

PART 344--TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE

    5. The authority citation for 21 CFR part 344 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.


    6. Section 344.3 is amended by adding paragraphs (c) and (d) to 
read as follows:


Sec. 344.3  Definitions.

* * * * *
    (c) Water-clogged ears. The retention of water in the external ear 
canal, thereby causing discomfort and a sensation of fullness or 
hearing impairment.
    (d) Ear drying aid. A drug used in the external ear canal to help 
dry water-clogged ears.

    7. Section 344.10 is amended by revising the section heading to 
read as follows:


Sec. 344.10  Earwax removal aid active ingredient.

* * * * *

    8. Section 344.12 is added to subpart B to read as follows:


Sec. 344.12  Ear drying aid active ingredient.

    The active ingredient of the product consists of isopropyl alcohol 
95 percent in an anhydrous glycerin 5 percent base.

    9. Section 344.50 is amended by revising the section heading and by 
removing paragraph (e) to read as follows:


Sec. 344.50  Labeling of earwax removal aid drug products.

* * * * *

    10. Section 344.52 is added to subpart C to read as follows:


Sec. 344.52  Labeling of ear drying aid drug products.

    (a) Statement of identity. The labeling of the product contains the 
established name of the drug, if any, and identifies the product as an 
``ear drying aid.''
    (b) Indications. The labeling of the product states, under the 
heading ``Use,'' the following: ``dries water in the ears'' (optional, 
which may be followed by: ``and relieves water-clogged ears'') (which 
may be followed by any or all of the following: ``after: [bullet] \1\ 
swimming [bullet] showering [bullet] bathing [bullet] washing the 
hair''). Other truthful and nonmisleading statements, describing only 
the indications for use that have been established and listed in 
paragraph (b) of this section, may also be used, as provided in 
Sec. 330.1(c)(2) of this chapter, subject to the provisions of section 
502 of the Federal Food, Drug, and Cosmetic Act (the act) relating to 
misbranding and the prohibition in section 301(d) of the act against 
the introduction or delivery for introduction into interstate commerce 
of unapproved new drugs in violation of section 505(a) of the act.
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    \1\ See Sec. 201.66(b)(4) of this chapter.
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    (c) Warnings. The labeling of the product contains the following 
warnings under the heading ``Warnings'':
    (1) ``Flammable [in bold type]: Keep away from fire or flame.''
    (2) ``Do not use [in bold type] in the eyes.''
    (3) ``Ask a doctor before use if you have [in bold type] [bullet] 
ear drainage or discharge [bullet] pain, irritation, or rash in the ear 
[bullet] had ear surgery [bullet] dizziness.''
    (4) ``Stop use and ask a doctor if [in bold type] irritation (too 
much burning) or pain occurs.''
    (d) Directions. The labeling of the product contains the following 
statement under the heading ``Directions'': [optional, bullet] ``apply 
4 to 5 drops in each affected ear.''

    Dated: July 31, 2000.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 00-19992 Filed 8-9-00; 8:45 am]
BILLING CODE 4160-01-F