[Federal Register Volume 72, Number 43 (Tuesday, March 6, 2007)]
[Rules and Regulations]
[Pages 9849-9852]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-3808]


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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; 
Amendment to the Monograph

AGENCY:  Food and Drug Administration, HHS.

ACTION:  Final rule.

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SUMMARY:  The Food and Drug Administration (FDA) is issuing a final 
rule amending 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 did not 
receive any comments or data in response to its previously proposed 
rule to include this combination. This final rule is part of FDA's 
ongoing review of OTC drug products.

DATES:  Effective Date: This regulation is effective April 5, 2007.

FOR FURTHER INFORMATION CONTACT:  Michael L. Chasey, Center for Drug

[[Page 9850]]

Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, MS 5411, Silver Spring, MD 20993, 301-796-
2090.

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 an external 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 
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 menthol in the monograph for 
controlling dandruff. The Miscellaneous External Panel further noted 
that menthol's activity to temporarily relieve itching should not be 
considered the same as 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 a FM for OTC dandruff, seborrheic dermatitis, and psoriasis drug 
products (21 CFR part 358, subpart H). The FM includes a discussion of 
a study comparing two shampoo formulations for relief of scalp itching 
associated with dandruff. One formulation contained the combination of 
9 percent coal tar solution and 1.5 percent menthol and the other 
contained coal tar as a single ingredient. FDA determined that the 
study had a number of major design flaws. For example, the study did 
not include a group of subjects who only used menthol. Thus, the 
individual contributions of coal tar and menthol to the effectiveness 
of the combination product could not be determined from the study. In 
addition, the statistical analysis of the study results was not valid. 
FDA concluded that the study did not demonstrate that the combination 
product offers any advantage over the product containing only coal tar. 
Thus, FDA concluded that the coal tar-menthol combination is not 
generally recognized as safe and effective (GRASE) for the control of 
dandruff based on the study. This combination was placed in a list of 
active ingredients found not to be GRASE (21 CFR 310.545(d)(3)).

II. Amendment of the Dandruff, Seborrheic Dermatitis, and Psoriasis FM

    In 1993, FDA received a petition containing new data in support of 
the combination of coal tar and menthol for the relief of scalp itching 
associated with dandruff. This new study addressed the concerns raised 
by FDA with the original study in the FM. The new study was a three-arm 
study, so the effectiveness of the individual ingredients could be 
properly compared to the combination product. In addition, the 
appropriate statistics were used to analyze the data. The study shows 
that both menthol alone as well as the combination of menthol and coal 
tar provide greater itch relief than coal tar alone at 5, 15, and 30 
minutes after shampooing and that the differences at each timepoint 
were statistically significant. Although menthol alone provides itch 
relief, FDA has no data to support menthol as a single active 
ingredient for general relief and control of the non-pruritic symptoms 
of dandruff (e.g., scaling). Thus, in the Federal Register of December 
9, 2005 (70 FR 73178), FDA published a proposed rule (PR) to amend the 
FM for OTC dandruff, seborrheic dermatitis, and psoriasis drug products 
to include the combination of 1.8 percent coal tar solution and 1.5 
percent menthol as GRASE in a shampoo drug product to control dandruff 
and relieve scalp itching associated with dandruff.
    FDA did not receive any comments or data in response to the 
proposed amendment to the final rule. Therefore, in this final rule, 
FDA is adding the combination of 1.8 percent coal tar and 1.5 percent 
menthol to Sec.  358.720 (21 CFR 358.720) and removing the combination 
from Sec.  310.545(d)(3) (21 CFR 310.545(d)(3)). As proposed, FDA is 
also adding new Sec.  358.760 (21 CFR 358.760) to describe the labeling 
for this combination. It reads as follows:
     Statement of identity (Sec.  358.760(a)(1)): ``dandruff/
anti-itch shampoo'' or ``antidandruff/anti-itch shampoo''
     Indication (Sec.  358.760(b)(1) and (b)(2)): ``[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''
     Warnings (Sec.  358.760(c)(1) and (c)(2)): those listed in 
Sec.  358.750(c)(1) and (c)(2)
     Directions (Sec.  358.760(d)(1)): ``[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''
    Any OTC dandruff, seborrheic dermatitis, or psoriasis drug product 
containing this combination of ingredients that is initially introduced 
or initially delivered for introduction into interstate commerce after 
the effective date of this final rule and is not in compliance with the 
regulations is subject to regulatory action.
    FDA is adding the combination of 1.8 percent coal tar and 1.5 
percent menthol and corresponding labeling and is also revising Sec.  
358.720(a) to correct an error. Section 358.720(a) references ``sulfur 
identified in Sec.  358.710(a)(6),'' but the paragraph should reference 
``sulfur identified in Sec.  358.710(a)(7).'' This error was introduced 
when micronized selenium sulfide was added to the monograph and Sec.  
358.710(a) was renumbered (58 FR 17554 and 59 FR 4000).

III. Analysis of Impacts

    FDA has examined the impacts of the final rule under Executive 
Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the 
Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1501 et seq.). 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

[[Page 9851]]

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 concludes that this final rule is consistent with the 
principles set out in Executive Order 12866 and in these two statutes. 
This final rule is not a significant regulatory action as defined by 
the Executive order and so is not subject to review under the Executive 
order. As discussed in this section, FDA has determined that this final 
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 final rule because the 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 $118 million, using the most current (2004) 
Implicit Price Deflator for the Gross Domestic Product.
    The purpose of this final 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 optional. Thus, this final rule 
will not impose a significant economic burden on affected entities. 
Therefore, FDA certifies that this final 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)).

IV. Paperwork Reduction Act of 1995

    FDA 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 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)).

V. 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.

VI. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the rule 
will have a preemptive effect on State law. Section 4(a) of the 
Executive order requires agencies to ``construe * * * a Federal statute 
to preempt State law only where the statute contains an express 
preemption provision or there is some other clear evidence that the 
Congress intended preemption of State law, or where the exercise of 
State authority conflicts with the exercise of Federal authority under 
the Federal statute.'' Section 751 of the Federal Food, Drug, and 
Cosmetic Act (the act) (21 U.S.C. 379r) is an express preemption 
provision. Section 751(a) of the act (21 U.S.C. 379r(a)) provides that:

    * * * no State or political subdivision of a State may establish 
or continue in effect any requirement--* * * (1) that relates to the 
regulation of a drug that is not subject to the requirements of 
section 503(b)(1) or 503(f)(1)(A); and (2) that is different from or 
in addition to, or that is otherwise not identical with, a 
requirement under this Act, the Poison Prevention Packaging Act of 
1970 (15 U.S.C. 1471 et seq.), or the Fair Packaging and Labeling 
Act (15 U.S.C. 1451 et seq.).

Currently, this provision operates to preempt States from imposing 
requirements related to the regulation of nonprescription drug 
products. (See Section 751(b) through (e) of the act for the scope of 
the express preemption provision, the exemption procedures, and the 
exceptions to the provision.)
    This final rule amends the FM for 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. Although this final rule has a preemptive 
effect, in that it precludes States from promulgating requirements 
related to labeling for OTC dandruff, seborrheic dermatitis, and 
psoriasis drug products that are different from or in addition to, or 
not otherwise identical with a requirement in the final rule, this 
preemptive effect is consistent with what Congress set forth in section 
751 of the act. Section 751(a) of the act displaces both State 
legislative requirements and State common law duties. We also note that 
even where the express preemption provision is not applicable, implied 
pre-emption may arise (see Geier v. American Honda Co., 529 US 861 
(2000)).
    FDA believes that the preemptive effect of the final rule is 
consistent with Executive Order 13132. Section 4(e) of the Executive 
order provides that ``when an agency proposes to act through 
adjudication or rulemaking to preempt State law, the agency shall 
provide all affected State and local officials notice and an 
opportunity for appropriate participation in the proceedings.''
    On January 18, 2007, FDA's Division of Federal and State Relations 
provided notice via fax and email transmission to elected officials of 
State governments and their representatives of national organizations. 
The notice provided the States with further opportunity for input on 
the rule. It advised the States of the publication of the December 9, 
2005, proposed rule and encouraged State and local governments to 
review the notice and to provide any comments to the docket (2005N-
0448) by a date 30 days from the date of the letter (i.e., by February 
20, 2007), or to contact certain named individuals. FDA received no 
comments in response to this notice. The notice has been filed in the 
above numbered docket.

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.


0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR parts 
310 and 358 are amended as follows:

PART 310--NEW DRUGS

0
1. The authority citation for 21 CFR part 310 continues to read as 
follows:


[[Page 9852]]


    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.


0
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 April 5, 2007.

PART 358--MISCELLANEOUS EXTERNAL DRUG PRODUCTS FOR OVER-THE-COUNTER 
HUMAN USE

0
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.


0
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)(7) 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.

0
5. New Sec.  358.760 is added 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 the 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: February 26, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-3808 Filed 3-5-07; 8:45 am]
BILLING CODE 4160-01-S