[Federal Register: March 6, 2007 (Volume 72, Number 43)]
[Rules and Regulations]
[Page 9849-9852]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06mr07-6]
=======================================================================
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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