[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