[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]
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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.
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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