[Federal Register Volume 70, Number 236 (Friday, December 9, 2005)]
[Proposed Rules]
[Pages 73178-73181]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-23839]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 310 and 358
[Docket No. 2005N-0448]
RIN 0910-AF49
Dandruff, Seborrheic Dermatitis, and Psoriasis Drug Products
Containing Coal Tar and Menthol for Over-the-Counter Human Use;
Proposed Amendment to the Monograph
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is issuing a proposed
rule to amend the final monograph (FM) for over-the-counter (OTC)
dandruff, seborrheic dermatitis, and psoriasis drug products to include
the combination of 1.8 percent coal tar solution and 1.5 percent
menthol in a shampoo drug product to control dandruff. FDA is issuing
this proposed rule after considering information submitted in a citizen
petition. This proposal is part of FDA's ongoing review of OTC drug
products.
DATES: Submit written or electronic comments by March 9, 2006. See
section IX of this document for the proposed effective date of any
final rule that may publish based on this proposal.
ADDRESSES: You may submit comments, identified by Docket No. 2005N-0448
and RIN 0910-AF49, by any of the following methods:
Electronic Submissions
Submit electronic comments in the following ways:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
Agency Web site: http://www.fda.gov/dockets/ecomments.
Follow the instructions for submitting comments on the agency Web site.
Written Submissions
Submit written submissions in the following ways:
FAX: 301-827-6870.
Mail/Hand delivery/Courier [For paper, disk, or CD-ROM
submissions]: Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
To ensure more timely processing of comments, FDA is no longer
accepting comments submitted to the agency by e-mail. FDA encourages
you to continue to submit electronic comments by using the Federal
eRulemaking Portal or the agency Web site, as described in the
Electronic Submissions portion of this paragraph.
Instructions: All submissions received must include the agency name
and Docket No. 2005N-0448. All comments received may be posted without
change to http://www.fda.gov/ohrms/dockets/default.htm, including any
personal information provided. For additional information on submitting
comments, see the ``Comments'' heading of the SUPPLEMENTARY INFORMATION
section of this document.
Docket: For access to the docket to read background documents or
comments received, go to http://www.fda.gov/dockets/default.htm and
insert the docket number, found in brackets in the heading of this
document, into the ``Search'' box and follow the prompts and/or go to
the Division of Dockets Management, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Michael L. Koenig, 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 December 4, 1979 (44 FR 69768), FDA
published an advance notice of proposed rulemaking (ANPR) to establish
a monograph for OTC external analgesic drug products. The ANPR includes
the recommendations of the Advisory Review Panel on OTC Topical
Analgesic, Antirheumatic, Otic, Burn, and Sunburn Prevention and
Treatment Drug Products (the Topical Analgesic Panel). The Topical
Analgesic Panel concluded that menthol is safe and effective for use as
an OTC external antipruritic (anti-itch) ingredient in concentrations
of 1.0 percent or less and as a topical counterirritant in
concentrations exceeding 1.25 percent up to 16 percent. In the Federal
Register of February 8, 1983 (48 FR 5852), FDA's proposed monograph, or
tentative final monograph (TFM), for OTC external analgesic drug
products included menthol as an antipruritic ingredient at
[[Page 73179]]
concentrations from 0.1 percent to 1.0 percent.
In the Federal Register of December 3, 1982 (47 FR 54646), FDA
published an ANPR to establish a monograph for OTC dandruff, seborrheic
dermatitis, and psoriasis drug products. The ANPR includes the
recommendations of the Advisory Review Panel on OTC Miscellaneous
External Drug Products (the Miscellaneous External Panel) concerning
OTC drug products for the control of dandruff, seborrheic dermatitis,
and psoriasis. The Miscellaneous External Panel recommended coal tar
preparations as safe and effective for use as shampoos for controlling
dandruff. The Miscellaneous External Panel also concluded that menthol
is safe at concentrations of 0.04 to 1.5 percent, but that there were
insufficient effectiveness data to include it in the monograph for
controlling dandruff. The Miscellaneous External Panel further noted
that the temporary relief of itching does not amount to control of
dandruff.
In the Federal Register of July 30, 1986 (51 FR 27346), FDA
published its TFM for OTC dandruff, seborrheic dermatitis, and
psoriasis drug products. No new information was submitted for menthol.
Therefore, menthol was not included in the TFM.
In the Federal Register of December 4, 1991 (56 FR 63554), FDA
issued an FM for OTC dandruff, seborrheic dermatitis, and psoriasis
drug products in part 358, subpart H (21 CFR part 358, subpart H). The
FM included discussion of a study comparing a shampoo product
containing the combination of 9 percent coal tar solution and 1.5
percent menthol versus a shampoo containing only the coal tar for
relieving scalp itching associated with dandruff (Ref. 1). FDA
determined that the study had a number of major flaws and did not
demonstrate that the combination product offers any advantage over the
product containing only coal tar (56 FR 63554 at 63562 to 63564).
Therefore, FDA concluded that the coal tar-menthol combination is not
generally recognized as safe and effective (GRASE) for the control of
dandruff and placed this combination in a list of active ingredients
found not to be GRASE (21 CFR 310.545(d)(3)).
II. FDA's Tentative Conclusions on the Petition
In 1993, FDA received a petition (Ref. 2) to amend the FM for OTC
dandruff, seborrheic dermatitis, and psoriasis drug products to include
the combination of 9 percent coal tar solution and 1.5 percent menthol
in a shampoo drug product to relieve scalp itching associated with
dandruff. The petitioner subsequently clarified that the coal tar
concentration of 9 percent was actually 9 percent, on a volume-to-
volume basis, of a 20 percent coal tar solution, on a weight-to-volume
basis. Thus, the final concentration of the coal tar solution used in
the study was 1.8 percent on a weight-to-volume basis (Ref. 3). The
petition includes results of a three-arm clinical study evaluating the
effectiveness of the ingredients in combination compared to 1.8 percent
coal tar alone and 1.5 percent menthol alone. Both menthol alone and
the combination of coal tar and menthol provided additional itch relief
at 5, 15, and 30 minutes over coal tar alone, and the difference in
itch relief was statistically significant (p <= 0.05). The study did
not examine relief of scaling (i.e., control of dandruff). FDA
tentatively concludes that this study supports the combination of 1.8
percent coal tar solution and 1.5 percent menthol in a shampoo to
provide more or additional relief of itching associated with dandruff
over 1.8 percent coal tar alone. FDA's detailed comments and evaluation
of the study are on file in the Division of Dockets Management (Ref.
4).
III. FDA's Proposal
Based on the study submitted in the petition and FDA's previous
conclusion that coal tar is GRASE for the control of dandruff, FDA
believes the combination of 1.8 percent coal tar and 1.5 percent
menthol in a shampoo is GRASE to control dandruff and relieve itching
associated with dandruff. FDA proposes to include this new combination
in Sec. 358.720 and remove the combination from Sec. 310.545(d)(3).
Because data on a range of concentrations for coal tar and menthol have
not been submitted, FDA is proposing to amend the FM to include only
the concentration of each active ingredient used in the study. Although
the 1.5 percent concentration for menthol exceeds the 1.0 percent
maximum currently proposed for the ingredient as an antipruritic (see
proposed Sec. 348.10(b)(6), 48 FR 5852 at 5867), this use of menthol
is different, because the product will be applied to hair that has been
thoroughly wetted and subsequently rinsed. Furthermore, the menthol is
likely diluted to below 1.0 percent concentration immediately. FDA is
not proposing menthol as a single active ingredient for the control or
relief of symptoms of dandruff because FDA has not received any data
demonstrating that menthol alone is GRASE for this indication.
FDA is proposing that labeling for this combination in proposed
Sec. 358.760 be as follows:
Statement of identity: ``dandruff/anti-itch shampoo'' or
``antidandruff/anti-itch shampoo'' (proposed Sec. 358.760(a)(1))
Indication: ``[bullet] [select one of the following: `for
relief of' or `controls'] the symptoms of dandruff [bullet] [select one
of the following: `additional' or `extra'] relief of itching due to
dandruff'' (proposed Sec. 358.760(b)(1) and (b)(2))
Warnings: those listed in Sec. 358.750(c)(1) and (c)(2)
(proposed Sec. 358.760(c))
Directions: ``[bullet] wet hair [bullet] apply shampoo and
work into a lather [bullet] rinse thoroughly [bullet] for best results,
use at least twice a week or as directed by a doctor'' (proposed Sec.
358.760(d)(1))
FDA believes the proposed labeling for coal tar-menthol combination
drug products reflects the scientific data, which demonstrate the
combination provides additional itch relief over coal tar alone. FDA
proposes a statement of identity for this product that reflects the
antidandruff action of coal tar as well as the anti-itch action of
menthol. When comparing coal tar products labeled as ``dandruff
shampoo'' with combination coal tar-menthol products labeled as
``dandruff/anti-itch shampoo,'' consumers will be informed that the
combination products contain menthol for more itch relief than provided
by coal tar alone.
FDA also proposes to include this additional anti-itch action under
the ``Uses'' heading in the Drug Facts labeling. FDA is proposing a
similar indication statement for coal tar-menthol combination products
as that included in the dandruff monograph for other coal tar products
(Sec. 358.750(b)). In addition, FDA proposes a second indication
statement for coal tar-menthol combination products only: ``[bullet]
[select one of the following: `additional' or `extra'] relief of
itching due to dandruff''. This indication reflects the data from the
submitted study (Ref. 2) by informing consumers that the combination
product provides more itch relief than coal tar alone.
Because the warnings for menthol in the proposed rule for OTC
external analgesic drug products (48 FR 5852 at 5868) are similar to
those for coal tar in the dandruff monograph (Sec. 358.750(c)(1) and
(c)(2)), FDA proposes the same warnings for the combination as for coal
tar alone. The directions proposed for the combination product specify
that the product be a shampoo applied to wetted hair and thoroughly
removed
[[Page 73180]]
from the scalp after brief exposure. FDA is not proposing to include
formulations that are applied and left on the skin or scalp (e.g.,
creams, ointments, lotions, or hairgrooms) because FDA has only
reviewed safety and effectiveness data for coal tar-menthol combination
drug products in a shampoo.
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), 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 may have 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.
Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires
that agencies prepare a written statement, which includes an assessment
of costs and benefits, before proposing ``any rule that includes any
Federal mandate that may result in the expenditure by State, local, and
tribal governments, in the aggregate, or by the private sector, of $100
million or more (adjusted annually for inflation) in any one year.''
FDA tentatively concludes that this proposed rule is consistent
with the principles set out in Executive Order 12866 and in these two
statutes. This proposed rule is not a significant regulatory action as
defined by the Executive order and so is not subject to review under
the Executive order. As discussed in this section of the document, FDA
has tentatively determined that this proposed rule will not have
significant economic impact on a substantial number of small entities
under the Regulatory Flexibility Act. The Unfunded Mandates Reform Act
does not require FDA to prepare a statement of costs and benefits for
this proposed rule because the proposed rule is not expected to result
in any 1-year expenditure that would meet or exceed $100 million
adjusted for inflation. The current threshold after adjustment for
inflation is about $115 million, using the most current (2003) Implicit
Price Deflator for the Gross Domestic Product.
The purpose of this proposed rule is to allow an additional
combination of active ingredients for OTC antidandruff drug products.
Manufacturers can reformulate their OTC antidandruff drug products that
contain coal tar to include the combination or can manufacture a new
combination product containing coal tar and menthol. Reformulating or
manufacturing a new combination product might result in additional
product sales but, in either case, is completely optional. Thus, this
proposed rule will not impose a significant economic burden on affected
entities. Therefore, FDA certifies that this proposed rule will not
have a significant economic impact on a substantial number of small
entities. No further analysis is required under the Regulatory
Flexibility Act (5 U.S.C. 605(b)).
FDA invites public comment regarding any substantial or significant
economic impact that this proposed rule would have on manufacturers of
OTC drug products for the control of dandruff. Types of impact may
include, but are not limited to, costs associated with manufacturing,
labeling, or repackaging. Comments regarding the impact of this
proposed rule should be accompanied by appropriate documentation. FDA
is providing a period of 90 days, from the date of publication of this
proposed rule in the Federal Register, to develop and submit comments
on this subject. FDA will evaluate any comments and supporting data
that are received and will reassess the economic impact of this
proposed rule in the preamble to the final 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 statements 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
FDA 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.
VII. Federalism
FDA has analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. FDA has determined that
the proposed rule does not contain policies that have substantial
direct effects on the States, on the relationship between the National
Government and the States, or on the distribution of power and
responsibilities among the various levels of government. Accordingly,
FDA tentatively concludes that the proposed rule does not contain
policies that have federalism implications as defined in the Executive
order and, consequently, a federalism summary impact statement has not
been prepared.
VIII. Request for Comment
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this proposal
and on FDA's economic impact determination. Submit a single copy of
electronic comments or two paper copies of any mailed comments, except
that individuals may submit one paper copy. Comments are to be
identified with the docket number found in brackets in the heading of
this document. Received comments may be seen in the Division of Dockets
Management between 9 a.m. and 4 p.m., Monday through Friday.
IX. Proposed Effective Date
FDA is proposing that any final rule that may issue based on this
proposal become effective 30 days after its date of publication in the
Federal Register.
X. References
The following references are on display in the Division of Dockets
Management (see ADDRESSES) under Docket No. 1982N-0214 and may be seen
by interested persons between 9 a.m. and 4 p.m., Monday through Friday.
1. Comment No. RPT.
2. Comment No. PR 1.
3. Comment No. LET 13.
4. Comment No. LET 14.
List of Subjects
21 CFR Part 310
Administrative practice and procedure, Drugs, Labeling, Medical
devices, Reporting and recordkeeping requirements.
21 CFR Part 358
Labeling, Over-the-counter drugs.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner
[[Page 73181]]
of Food and Drugs, it is proposed that 21 CFR parts 310 and 358 be
amended as follows:
PART 310--NEW DRUGS
1. The authority citation for 21 CFR part 310 continues to read as
follows:
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.
2. Section 310.545 is amended by revising paragraph (d)(3) to read
as follows:
Sec. 310.545 Drug products containing certain active ingredients
offered over-the-counter (OTC) for certain uses.
* * * * *
(d) * * *
(3) December 4, 1992, for products subject to paragraph (a)(7) of
this section that contain menthol as an antipruritic in combination
with the antidandruff ingredient coal tar identified in Sec.
358.710(a)(1) of this chapter. This section does not apply to products
allowed by Sec. 358.720(b) of this chapter after January 9, 2006.
* * * * *
PART 358--MISCELLANEOUS EXTERNAL DRUG PRODUCTS FOR OVER-THE-COUNTER
HUMAN USE
3. The authority citation for 21 CFR part 358 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
4. Section 358.720 is revised to read as follows:
Sec. 358.720 Permitted combinations of active ingredients.
(a) Combination of active ingredients for the control of dandruff.
Salicylic acid identified in Sec. 358.710(a)(4) may be combined with
sulfur identified in Sec. 358.710(a)(6) provided each ingredient is
present within the established concentration and the product is labeled
according to Sec. 358.750.
(b) Combination of control of dandruff and external analgesic
active ingredients. Coal tar identified in Sec. 358.710(a)(1) may be
used at a concentration of 1.8 percent coal tar solution, on a weight-
to-volume basis, in combination with menthol, 1.5 percent, in a shampoo
formulation provided the product is labeled according to Sec. 358.760.
5. New Sec. 358.760 is added to subpart H to read as follows:
Sec. 358.760 Labeling of permitted combinations of active ingredients
for the control of dandruff.
The statement of identity, indications, warnings, and directions
for use, respectively, applicable to each ingredient in the product may
be combined to eliminate duplicative words or phrases so that the
resulting information is clear and understandable.
(a) Statement of identity. For a combination drug product that has
an established name, the labeling of the product states the established
name of the combination drug product, followed by the statement of
identity for each ingredient in the combination, as established in the
statement of identity sections of the applicable OTC drug monographs.
(1) Combinations of control of dandruff and external analgesic
active ingredients in Sec. 358.720(b). The label states ``dandruff/
anti-itch shampoo'' or ``antidandruff/anti-itch shampoo''.
(2) [Reserved]
(b) Indications. The labeling of the product states, under the
heading ``Uses,'' one or more of the phrases listed in this paragraph
(b), as appropriate. Other truthful and nonmisleading statements,
describing only the uses that have been established and listed in this
paragraph (b), 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.
(1) Combinations of control of dandruff and external analgesic
active ingredients in Sec. 358.720(b). The labeling states ``[bullet]
[select one of the following: `for relief of' or `controls'] the
symptoms of dandruff [bullet] [select one of the following:
`additional' or `extra'] relief of itching due to dandruff''.
(2) The following terms or phrases may be used in place of or in
addition to the words ``for relief of'' or ``controls'' in the
indications in paragraph (b)(1) of this section: ``fights,''
``reduces,'' ``helps eliminate,'' ``helps stop,'' ``controls recurrence
of,'' ``fights recurrence of,'' ``helps prevent recurrence of,''
``reduces recurrence of,'' ``helps eliminate recurrence of,'' ``helps
stop recurrence of''.
(3) The following terms may be used in place of the words ``the
symptoms of'' in the indication in paragraph (b)(1) of this section:
``scalp'' (select one or more of the following: ``itching,''
``irritation,'' ``redness,'' ``flaking,'' ``scaling'') ``associated
with''.
(c) Warnings. The labeling of the product states, under the heading
``Warnings,'' the warning(s) listed in Sec. 358.750(c)(1) and (c)(2).
(d) Directions. The labeling of the product states, under the
heading ``Directions,'' directions that conform to the directions
established for each ingredient in the directions sections of the
applicable OTC drug monographs, unless otherwise stated in this
paragraph (d). When the time intervals or age limitations for
administration of the individual ingredients differ, the directions for
the combination product may not contain any dosage that exceeds those
established for any individual ingredient in the applicable OTC drug
monograph(s), and may not provide for use by any age group lower than
the highest minimum age limit established for any individual
ingredient.
(1) Combinations of control of dandruff and external analgesic
active ingredients in Sec. 358.720(b). The labeling states ``[bullet]
wet hair [bullet] apply shampoo and work into a lather [bullet] rinse
thoroughly [bullet] for best results, use at least twice a week or as
directed by a doctor''.
(2) [Reserved]
Dated: December 5, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-23839 Filed 12-8-05; 8:45 am]
BILLING CODE 4160-01-S