[Federal Register Volume 63, Number 138 (Monday, July 20, 1998)]
[Proposed Rules]
[Pages 38762-38765]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-19239]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 341

[Docket No. 76N-052T]
RIN 0910-AA01


Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug 
Products for Over-the-Counter Human Use; Proposed Amendment of Final 
Monograph for OTC Antitussive Drug Products

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of proposed rulemaking.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is issuing a notice of 
proposed rulemaking that would amend the final monograph for over-the-
counter (OTC) antitussive drug products (drug products that relieve 
cough) to revise the labeling warnings and directions for topical/
inhalant products containing the active ingredients camphor and/or 
menthol. New information indicates that use of these drug products near 
an open flame, in hot water, or in a microwave oven can cause the 
products to catch on fire and cause serious burns to the user. 
Therefore, the agency is proposing warnings and directions for safer 
use of these drug products by informing consumers not to expose the 
products to flame, hot water, or a microwave oven. This proposal is 
part of the ongoing review of OTC drug products conducted by FDA.

DATES: Submit written comments by October 19, 1998; written comments on 
the agency's economic impact determination by October 19, 1998. FDA is 
proposing that any final rule that may issue based on this proposal 
become effective 12 months after its date of publication in the Federal 
Register.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Elizabeth A. Ryland, Center for Drug 
Evaluation and Research (HFD-560), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-2222.

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of September 9, 1976 (41 FR 38312 at 
38343), the Advisory Review Panel on OTC Cold, Cough, Allergy, 
Bronchodilator, and Antiasthmatic Drug Products (the Panel) recommended 
that the single ingredients camphor and menthol for topical/inhalant 
antitussive use be classified in Category III (available data are 
insufficient to classify as safe and effective, and further testing is 
required). The Panel based its recommendations on a lack of 
effectiveness data, but determined that these products are safe (41 FR 
38312 at 38344 and 38349 to 38352). The Panel was not aware of and did 
not discuss any information concerning possible safety hazards 
occurring when these products are placed near a flame, into containers 
of hot water, or in a microwave oven. The Panel recommended the 
following directions for topical/inhalant use for camphor and menthol:
     * * * 1 tablespoonful of solution per quart of water is added 
directly to the water in a hot steam vaporizer, bowl, or washbasin; 
or 2 teaspoonfuls of solution per pint of water are added to an open 
container of boiling water. Breathe in vapors during the period of 
medicated steam generation. May be repeated 3 times daily.
    In the final monograph for OTC antitussive drug products (52 FR 
30042 at 30045 to 30046, August 12, 1987), the agency provided the 
following directions in Sec. 341.74(d)(2)(i) and (d)(2)(ii) (21 CFR 
341.74(d)(2)(i) and (d)(2)(ii)) for products containing the single 
ingredient camphor or menthol for ointment vehicle use based on 
additional clinical studies that supported effectiveness:
     * * * Adults and children 2 to under 12 years of age: Rub on 
the throat and chest as a thick layer. The area of application may 
be covered with a warm, dry cloth if desired. However, clothing 
should be left loose about the throat and chest to help the vapors 
rise to reach the nose and mouth. Applications may be repeated up to 
three times daily or as directed by a doctor. Children under 2 years 
of age: consult a doctor.
For products containing the single ingredient camphor or menthol for 
steam inhalation use, the agency provided the following directions in 
Sec. 341.74(d)(2)(iv) and (d)(2)(v), based on additional clinical 
studies that supported effectiveness:
     * * * Adults and children 2 to under 12 years of age: Add 1 
tablespoonful of solution, for each quart of water, directly to the 
water in a hot steam vaporizer, bowl, or wash basin; or add 1\1/2\ 
teaspoonsful of solution, for each pint of water, to an open 
container of boiling water. Breathe in the medicated vapors. May be 
repeated up to three times daily or as directed by a doctor. 
Children under 2 years of age: consult a doctor.
    When the final monograph was published, the agency was not aware of 
safety problems occurring when products containing camphor and/or 
menthol are added to hot water. Since that time, the agency has 
received new information (Refs. 1, 2, and 3) that indicates that the 
current warnings and directions may not be adequate and that safety 
concerns (e.g., burns caused by flashing) could arise if these products 
are heated near an open flame, in a container of hot water, or in a 
microwave oven. From 1983 to mid-1997, 34 fire-related events from 
usage of antitussive drug products containing camphor and menthol were 
reported (Refs. 2 and 3). Twenty-one fire-related events concerned a 
combination of camphor and menthol in an ointment vehicle. This product 
when added to hot water in a container on the stove, or when added to 
water and heated in a microwave oven, caused flashing and severe burns. 
One of the 21 events involved adding the product to hot water in a 
vaporizer. An additional 11 events concerned heating products that were 
combinations of camphor and menthol in an alcohol-based solution. These 
products, like the products in the ointment vehicles, also caused 
flashing and burns when placed in hot water or

[[Page 38763]]

heated in a microwave oven. For example, a product flashed from the top 
of its container when it was opened close to the gas stove where water 
had been heated, but the gas flame had been extinguished. In still 
another fire-related event (the 33d event), the alcohol-based solution 
product was poured over lava rocks in a sauna. The product ignited, 
caught the consumer's bathrobe on fire, and caused burns over 65 
percent of her body. The last reported fire-related event involved the 
ointment product and the alcohol-based product added to water and 
heated together resulting in flashing and burns. No fire-related events 
were reported when these products were added to cold water in a hot 
steam vaporizer and then heated.
    In all 34 reported events, flashing occurred; in 5 events, the 
flashing caused first and second degree burns to the face, eyes, chest, 
shoulders, arms, and/or hands. In some instances, these burns may have 
caused permanent scarring or reduced vision. Some consumers treated 
themselves at home and others went to a physician's office, a clinic, a 
medical center, or an emergency room for treatment. One case required 
hospitalization.
    References
    (1) Food and Drug Administration Drug Product Reporting System, 
dated May 31, 1995, in OTC Vol. 04TFMA, Docket No. 76N-052T, Dockets 
Management Branch.
    (2) MEDWATCH: Adverse Event Reports dated 1983 to 1995 in OTC 
Vol. 04TFMA, Docket No. 76N-052T, Dockets Management Branch.
    (3) MEDWATCH: Adverse Event Reports dated 1995 to 1997 in OTC 
Vol. 04TFMA, Docket No. 76N-052T, Dockets Management Branch.

II. The Agency's Tentative Conclusions and Proposal

    The agency tentatively concludes that the case reports raise safety 
concerns that could be alleviated by providing consumers with 
additional warnings and directions for topical/inhalant OTC antitussive 
drug products that contain camphor and/or menthol. The agency also 
notes that the labeling on one manufacturer's currently marketed 
products (containing camphor and menthol) (Ref. 3) is similar to the 
labeling proposed in this document. The agency believes that consumers 
need to be informed not to expose these products to flame or a 
microwave oven, not to place the products in any container in which 
water is being heated, and to add to cool water when using a hot steam 
vaporizer. Accordingly, the agency is proposing to amend the final 
monograph for OTC antitussive drug products to expand the warnings 
against possible flammability or combustibility and a precaution to 
keep them away from fire or flame. Labeling may also tell consumers to 
close caps tightly and store containers at room temperature away from 
heat.
    The following information shall appear on any labeling that 
contains warnings and shall appear after the subheader ``Do Not Use:'' 
``near an open flame'', ``by adding to hot water'', ``in a microwave 
oven'', or ``in a container in which water is being heated, except when 
adding to cold water in only a hot steam vaporizer''.
    Additionally, the agency is proposing to amend the final monograph 
for OTC antitussive drug products to shorten and simplify the 
directions in Sec. 341.74(d)(2)(i), (d)(2)(ii), (d)(2)(iv), and 
(d)(2)(v) for products containing camphor or menthol for topical/
inhalation use. Further, the agency is proposing to add the following 
statements at the end of the directions: ``See important warnings about 
not using near a flame, in hot water, or in a microwave oven. Improper 
use may cause the mixture to splatter and cause burns.'' (Last two 
sentences to be highlighted in boldface type or contrasting color.)
     The agency is also proposing to add an additional revision to the 
directions in Sec. 341.74(d)(2)(iv) and (d)(2)(v) for products 
containing camphor or menthol for steam inhalation. The proposed 
revised directions inform users to add the solution directly to cold 
water in only a hot steam vaporizer. All suggestions to use the product 
in any other container have been deleted. This part of the proposed 
revised directions reads as follows:
     Adults and children 2 to under 12 years of age: Add 1 
tablespoonful of solution, for each quart of water, or add 1\1/2\ 
teaspoonsful of solution, for each pint of water, directly to cold 
water in only a hot steam vaporizer. Breathe in the medicated 
vapors. Use up to three times daily or as directed by a doctor. 
Children under 2 years of age: Consult a doctor.
     The agency is inviting comment on the specific wording of these 
warnings and directions, and the best way to convey this information to 
persons using these drug products.

III. Effective Date

    The agency is proposing that these new warnings and directions 
become effective 12 months after the date of publication of a final 
rule in the Federal Register. The agency believes that the 12-month 
effective date is needed because this period of implementation would 
allow many manufacturers to coordinate this change with routinely 
scheduled label printing and/or revisions as well as the new OTC drug 
product labeling format proposed in the Federal Register of February 
27, 1997 (62 FR 9024). The agency encourages manufacturers of OTC 
antitussive drug products to voluntarily implement this labeling as of 
the date of publication of this proposal because of the potential for 
safety problems. Manufacturers, however, should be aware of the 
possibility that FDA may change the wording of the warnings and/or 
directions as a result of comments filed in response to this proposal. 
Because FDA is encouraging that the proposed warnings and directions be 
used on a voluntary basis at this time, the agency advises that 
manufacturers will be given ample time after publication of a final 
rule to use up any labeling implemented in conformance with this 
proposal.

IV. Analysis of Impacts

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612). 
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 economic impact of a rule 
on small entities.
    Title II of the Unfunded Mandates Reform Act (2 U.S.C. 1501 et 
seq.) requires that agencies prepare a written statement and economic 
analysis before proposing any rule that may result in the expenditure 
in any 1 year by State, local, and tribal governments, in the 
aggregate, or by the private sector, of $100 million (adjusted annually 
for inflation).
    The agency believes that this proposed rule is consistent with the 
principles set out in the Executive Order and in these two statutes. 
The purpose of this proposed rule is to revise and improve the labeling 
(add additional warning and direction statements) for topical/inhalant 
products that contain camphor, menthol, or both ingredients. This 
revised labeling addresses the flammability of these products when used 
near an open flame, in hot water, or in a microwave oven, and is 
intended to provide consumers additional information to help ensure 
safer use of these products. Potential benefits include reduction in 
the number of flash

[[Page 38764]]

fires and serious burns when consumers use these products.
    This proposed rule would amend the final monograph for OTC 
antitussive drug products and would require some relabeling for 
topical/inhalant products that contain camphor, menthol, or both 
ingredients. The agency's Drug Listing System identifies approximately 
30 manufacturers and 79 marketers of over 100 stock keeping units (SKU) 
(individual products, packages, and sizes) of topical/inhalant 
antitussive drug products containing camphor, menthol, or both 
ingredients. There may be a few additional marketers and products that 
are not identified in the sources FDA reviewed.
    The agency estimates that relabeling costs of the type that would 
be required by this proposal generally average about $2,000 to $3,000 
per SKU. Assuming that there are about 110 affected OTC SKU's in the 
marketplace, total one-time costs of relabeling would be $220,000 to 
$330,000. The agency believes that actual costs would be lower for 
several reasons. First, most of the label changes will be made by 
private label manufacturers that tend to use relatively simple and less 
expensive labeling. Second, the agency is proposing a 12-month 
implementation period that would allow many manufacturers to coordinate 
this change with routinely scheduled label printing and/or revisions. 
Similarly, labeling changes for these products would not be required 
until the monograph amendment is issued and becomes effective. Thus, 
manufacturers would have time to use up existing labeling stocks and 
the relabeling costs would be mitigated. Third, manufacturers may be 
able to implement the new labeling required by this proposal at the 
same time that they implement the new labeling format proposed for OTC 
drug products (62 FR 9024). Thus, the relabeling costs resulting from 
two different but related final rules may be individually reduced by 
implementing both required changes at the same time.
    The agency considered but rejected a shorter implementation period. 
While the agency would like to have this new labeling in place as soon 
as possible, it considers a period less than 12 months difficult for 
some manufacturers to implement all of the labeling that would be 
required by this proposal.
    The proposed rule would not require any new reporting and 
recordkeeping activities. Therefore, no additional professional skills 
are needed. There are no other Federal rules that duplicate, overlap, 
or conflict with the proposed rule. The agency does not believe that 
there are any significant alternatives to the proposed rule that would 
reduce the economic impact of the rule on small entities and would 
still adequately provide for the safe and effective OTC use of 
antitussive topical/inhalant drug products that contain camphor, 
menthol, or both ingredients. For example, the agency considered a 
longer implementation period but concluded that the marginal reduction 
in costs associated with an implementation period greater than 12 
months could not be justified in light of the additional injuries that 
would likely occur. The agency also considered but rejected more 
permissive warning language but concluded that such language would not 
adequately reduce the number of adverse events and accidents.
     Based on current information, the agency does not believe that 
this proposed rule will have a significant economic impact on a 
substantial number of small entities, using the U.S. Small Business 
Administration designations for this industry (750 employees). As 
discussed above, FDA is aware of only 30 manufacturers affected by this 
rule, most of which are assumed to be small for the purposes of this 
analysis. In addition, the agency believes that any other unidentified 
manufacturer of these products is also likely to be a small entity. 
From information available to the agency, it appears that only one 
small entity manufactures more than three SKU's of these products. 
Based on the limited number of SKU's each manufacturer has to relabel, 
the cost for each manufacturer except one should be minimal.
    The analysis shows that this proposed rule is not economically 
significant under Executive Order 12866 and that the agency has made an 
effort to reduce the burden to small entities. In addition, this 
economic analysis, together with other relevant sections of this 
document, serves as the agency's initial regulatory flexibility 
analysis, as required under the Regulatory Flexibility Act. Finally, 
this analysis shows that the Unfunded Mandates Act does not apply to 
the proposed amendment because it would not result in an expenditure in 
any 1 year by State, local, and tribal governments, in the aggregate, 
or by the private sector, of $100 million.
    The agency invites public comment regarding any substantial or 
significant economic impact that this rulemaking would have on 
manufacturers of OTC antitussive topical/inhalant drug products that 
contain camphor, menthol, or both ingredients. Comments regarding the 
impact of this rulemaking on such manufacturers should be accompanied 
by appropriate documentation. The agency is providing a period of 90 
days from the date of publication of this proposed rulemaking in the 
Federal Register for comments to be developed and submitted. The agency 
will evaluate any comments and supporting data that are received and 
will reassess the economic impact of this rulemaking in the preamble to 
the final rule.
    In the Federal Register of February 27, 1997 (62 FR 9024), FDA 
proposed to establish a standardized format for the labeling of OTC 
drug products. When the agency finalizes the February 27, 1997, 
labeling rule, the agency will also amend the final version of this 
proposed rule, as needed, to conform to the final labeling rule.

V. Paperwork Reduction Act of 1995

    FDA tentatively concludes that the labeling requirements proposed 
in this document 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 proposed 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)).

 VI. Environmental Impact

    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.

VII. Request for Comment

    Interested persons may, on or before October 19, 1998, submit 
written comments to the Dockets Management Branch (address above). 
Written comments on the agency's economic impact determination may be 
submitted on or before October 19, 1998. Three copies of all comments 
are to be submitted, except that individuals may submit one copy. 
Comments are to be identified with the docket number found in brackets 
in the heading of this document and may be accompanied by a supporting 
memorandum or brief. Received comments may be seen in the office above 
between 9 a.m. and 4 p.m., Monday through Friday.

List of Subjects in 21 CFR Part 341

    Labeling, Over-the-counter drugs.

[[Page 38765]]

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that 21 CFR part 341 be amended as follows:

PART 341--COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC 
DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE

    1. The authority citation for 21 CFR part 341 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
    2. Section 341.74 is amended by adding paragraphs (c)(5)(iii), 
(c)(5)(iv), and (c)(5)(v), and revising paragraphs (d)(2)(i), 
(d)(2)(ii), (d)(2)(iv), and (d)(2)(v) to read as follows:


Sec. 341.74   Labeling of antitussive drug products.

* * * * *
     (c) * * *
    (5) * * *
    (iii) For any product containing camphor or menthol in a suitable 
ointment vehicle or for steam inhalation use.--(A) The labeling should 
contain an appropriate flammability signal word, e.g., ``extremely 
flammable,'' ``flammable,'' ``combustible,'' consistent with 16 CFR 
1500.3(b)(10).
    (B) ``Keep away from fire or flame.''
    (iv) For any product formulated in a volatile vehicle. ``Cap 
container tightly and store at room temperature away from heat.''
    (v) For any product with labeling that contains warnings, the 
following information shall appear after the subheader ``Do Not 
Use''.--(A) ``Near an open flame.''
    (B) ``By adding to hot water.''
    (C) ``In a microwave oven.''
    (D) ``In a container in which water is being heated, except when 
adding to cold water in only a hot steam vaporizer.''
    (d) * * *
    (2) * * *
    (i) For products containing camphor identified in Sec. 341.14(b)(1) 
in a suitable ointment vehicle. The product contains 4.7 to 5.3 percent 
camphor. Adults and children 2 to under 12 years of age: Rub on the 
throat and chest in a thick layer. Cover with a warm, dry cloth if 
desired. However, clothing should be loose about throat and chest to 
help vapors reach the nose and mouth. Use up to three times daily or as 
directed by a doctor. Children under 2 years of age: Consult a doctor. 
``See important warnings about not using near a flame, in hot water, or 
in a microwave oven. Improper use may cause the mixture to splatter and 
cause burns.'' (Last two sentences to be highlighted in bold type or 
contrasting color.)
    (ii) For products containing menthol identified in 
Sec. 341.14(b)(2) in a suitable ointment vehicle. The product contains 
2.6 to 2.8 percent menthol. Adults and children 2 to under 12 years of 
age: Rub on the throat and chest in a thick layer. Cover with a warm, 
dry cloth if desired. However, clothing should be loose about throat 
and chest to help vapors reach the nose and mouth. Use up to three 
times daily or as directed by a doctor. Children under 2 years of age: 
Consult a doctor. ``See important warnings about not using near a 
flame, in hot water, or in a microwave oven. Improper use may cause the 
mixture to splatter and cause burns.'' (Last two sentences to be 
highlighted in bold type or contrasting color.)
* * * * *
     (iv) For products containing camphor identified in 
Sec. 341.14(b)(1) for steam inhalation use. The product contains 6.2 
percent camphor. Adults and children 2 to under 12 years of age: Add 1 
tablespoonful of solution, for each quart of water, or add 1\1/2\ 
teaspoonsful of solution, for each pint of water, directly to cold 
water in only a hot steam vaporizer. Breathe in the medicated vapors. 
Use up to three times daily or as directed by a doctor. Children under 
2 years of age: Consult a doctor. ``See important warnings about not 
using near a flame, in hot water, or in a microwave oven. Improper use 
may cause the mixture to splatter and cause burns.'' (Last two 
sentences to be highlighted in bold type or contrasting color.)
     (v)  For products containing menthol identified in 
Sec. 341.14(b)(2) for steam inhalation use. The product contains 3.2 
percent menthol. Adults and children 2 to under 12 years of age: Add 1 
tablespoonful of solution, for each quart of water, or add 1\1/2\ 
teaspoonsful of solution, for each pint of water, directly to cold 
water in only a hot steam vaporizer. Breathe in the medicated vapors. 
Use up to three times daily or as directed by a doctor. Children under 
2 years of age: Consult a doctor. ``See important warnings about not 
using near a flame, in hot water, or in a microwave oven. Improper use 
may cause the mixture to splatter and cause burns.'' (Last two 
sentences to be highlighted in bold type or contrasting color.)

    Dated: July 8, 1998.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 98-19239 Filed 7-17-98; 8:45 am]
BILLING CODE 4160-01-F