[Federal Register Volume 68, Number 114 (Friday, June 13, 2003)]
[Rules and Regulations]
[Pages 35290-35293]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-14818]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 347

[Docket No. 78N-021A]
RIN 0910-AA01


Skin Protectant Drug Products for Over-the-Counter Human Use; 
Astringent Drug Products; Final Monograph; Direct Final Rule

AGENCY: Food and Drug Administration, HHS.

ACTION: Direct final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending the 
regulation that established conditions under which over-the-counter 
(OTC) skin protectant astringent drug products are generally recognized 
as safe and effective and not misbranded. This action revises some 
labeling for astringent drug products to be consistent with the final 
rule for OTC skin protectant drug products (68 FR 33362, June 4, 2003) 
and adds labeling for certain small packages (styptic pencils). This 
action is part of FDA's ongoing review of OTC drug products. Elsewhere 
in this issue of the Federal Register, FDA is publishing a companion 
proposed rule, under FDA's usual procedure for notice-and-comment 
rulemaking, to provide a procedural framework to finalize the

[[Page 35291]]

rule in the event the agency receives any significant adverse comments 
and withdraws this direct final rule.

DATES: 
    Effective Date: This rule is effective October 27, 2003.
    Compliance Dates: The compliance dates are either June 13, 2005, or 
the date of the first major labeling revision after the effective date 
of October 27, 2003, whichever occurs first.
    Comment Dates: Submit written comments by August 27, 2003. If no 
timely significant adverse comments are received, the agency will 
publish a document in the Federal Register before September 26, 2003, 
confirming the effective date of the direct final rule. If timely 
significant adverse comments are received, the agency will publish a 
document of significant adverse comments in the Federal Register and 
withdraw this direct final rule before September 26, 2003.

ADDRESSES: Submit written comments on the direct final rule to the 
Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments 
to http://www.fda.gov/dockets/ecomments.

FOR FURTHER INFORMATION CONTACT: Gerald M. Rachanow, Center for Drug 
Evaluation and Research (HFD-560), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-2307.

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of October 21, 1993 (58 FR 54458), FDA 
published a final monograph for OTC skin protectant astringent drug 
products in part 347 (21 CFR part 347), subpart A (the 1993 skin 
protectant final monograph). In the Federal Register of June 4, 2003 
(68 FR 33362), FDA published a final rule for OTC skin protectant drug 
products (the 2003 skin protectant final monograph) and revised the 
format of part 347. Subpart A was redesignated as ``General 
Provisions,'' and the astringent active ingredients (Sec.  347.10) and 
labeling (Sec.  347.50) were redesignated as Sec. Sec.  347.12 and 
347.52, respectively.
    Two ingredients (colloidal oatmeal and sodium bicarbonate) added to 
the skin protectant monograph are used as a soak, compress, or wet 
dressing similar to the astringent active ingredient aluminum acetate. 
In the 2003 skin protectant final monograph, the agency included a 
warning about soaking too long (Sec.  347.50(c)(7)) and included 
directions for colloidal oatmeal (Sec.  347.50(d)(2)) and sodium 
bicarbonate (Sec.  347.50(d)(3)) that are shorter than the directions 
for aluminum acetate (Sec.  347.52(d)(1)) and that are in the new OTC 
drug labeling format. In this direct final rule, the agency is adding 
this warning, shortening the directions for aluminum acetate drug 
products, and arranging these directions in the new OTC drug labeling 
format.
    Section 201.66(d)(10) (21 CFR 201.66(d)(10)) of the OTC drug 
labeling rule (64 FR 13254 at 13286, March 17, 1999) establishes a 
modified labeling format for small packages that need more than 60 
percent of their total surface area available to bear labeling to meet 
the requirements of Sec.  201.66(c)(1) through (c)(9) and (d)(1) 
through (d)(9). The agency stated in that rule that it would consider 
additional approaches for accommodating certain products in their 
respective monographs, taking into consideration the risks and benefits 
of the drug, the intended use, and the need to communicate limitations 
or restrictions about the use of the product to the target population 
(64 FR 13254 at 13270, March 17, 1999). The 2003 skin protectant final 
monograph included additional labeling exemptions for certain small 
packages (lip protectant products) that meet the size criteria 
established in Sec.  201.66(d)(10). The agency determined that lip 
protectant/lip balm products are typically packaged in small amounts, 
applied to limited areas of the body, have a high therapeutic index, 
carry extremely low risk in actual consumer use situations, provide a 
favorable public health benefit, require no specified dosage 
limitation, and require few specific warnings and no general warnings 
(e.g., pregnancy or overdose warnings).
    Consequently, the agency is now including additional labeling 
exemptions for certain small packages of skin protectant astringent 
drug products (styptic pencils) that meet the criteria established in 
Sec.  201.66(d)(10), taking into consideration the risks and benefits 
of the drug, the intended use, and the need to communicate limitations 
or restrictions about the use of the product to the target population. 
For the safety profile of styptic pencils, the agency considered the 
recommendations of the Advisory Review Panel on OTC Miscellaneous 
External Drug Products (the Panel). The Panel noted that ``In 75 years 
of marketing styptic pencils there have been [no] reported instances of 
human toxicity'' (47 FR 39412 at 39429, September 7, 1982). (The word 
``no'' was inadvertently left out of the September 7, 1982, 
publication, and the agency corrected this error in its notice of 
proposed rulemaking for OTC skin protectant astringent drug products 
(54 FR 13490 at 13493, April 3, 1989).) The Panel also stated that 
aluminum sulfate (the active ingredient in styptic pencils) ``has 
little, if any, cell permeability and exerts its effect on the cell 
surface.'' The only side effect the Panel noted was that application of 
the styptic pencil on a cut may result in some stinging. Thus, these 
products have an extremely low risk in actual consumer use situations, 
and the monograph only requires two general warnings (Sec.  
347.50(c)(1)) and no ingredient specific warnings.
    The agency also considered the factors listed previously that were 
the basis for labeling modifications for OTC lip protectant/lip balm 
drug products. Like those products, styptic pencils are packaged in 
small amounts, have a high therapeutic index and a favorable public 
health benefit (stop bleeding), would be used infrequently and on very 
limited areas of the body to stop bleeding of minor cuts from shaving, 
require minimal warnings (there is no pregnancy warning because this is 
a topical product), and have no specified dosage limitation (the 
directions for use are to apply to the affected area). For these 
reasons, the agency is including specific labeling provisions for 
certain small packages of skin protectant astringent drug products 
(styptic pencils) in this direct final rule.

II. Description of the Labeling Revisions

    The warning in Sec.  347.50(c)(7), when the colloidal oatmeal or 
sodium bicarbonate product is labeled for use as a soak, compress, or 
wet dressing, states: ``When using this product [bullet] in some skin 
conditions, soaking too long may overdry.'' The agency is adding this 
warning in new Sec.  347.52(c)(4) for products containing aluminum 
acetate when labeled for use as a soak, compress, or wet dressing. Our 
decision to revise the warning set forth in this direct final rule is 
based upon a finding that bathing can dry the skin out and exacerbate 
some conditions (as discussed in the 2003 skin protectant final 
monograph, 68 FR 33362 at 33367). Mandating a warning does not require 
a finding that any or all of the astringent drug products actually 
caused an adverse event, and FDA does not so find. Nor does FDA's 
mandate of a warning repudiate the OTC drug monograph under which the 
affected drug products have been lawfully marketed. Rather, as a 
consumer protection agency, FDA has determined that this revised 
warning is necessary to ensure that these OTC drug products continue to 
be safe and effective for their labeled indications under ordinary 
conditions of use as those terms are

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defined in the Federal Food, Drug, and Cosmetic Act.
    FDA's decision to act in an instance such as this one need not meet 
the standard of proof required to prevail in a private tort action 
(Glastetter v. Novartis Pharmaceuticals, Corp., 252 F.3d 986, 991 (8th 
Cir. 2001)). To mandate a warning, or take similar regulatory action, 
FDA need not show, nor do we allege, actual causation.
    The agency is revising the directions in Sec.  347.52(d)(1)(i) for 
aluminum acetate used as a soak to read: ``For use as a soak: [bullet] 
soak affected area for 15 to 30 minutes as needed, or as directed by a 
doctor [bullet] repeat 3 times a day or as directed by a doctor 
[bullet] discard solution after each use''. The agency is revising the 
directions in Sec.  347.52(d)(1)(ii) for aluminum acetate used as a 
compress or wet dressing to read: ``For use as a compress or wet 
dressing: [bullet] soak a clean, soft cloth in the solution [bullet] 
apply cloth loosely to affected area for 15 to 30 minutes [bullet] 
repeat as needed or as directed by a doctor [bullet] discard solution 
after each use''. The agency is also shortening the directions in Sec.  
347.52(d)(3) for products containing witch hazel to read: ``apply as 
often as needed''.
    The agency is adding new Sec.  347.52(e) for products containing 
aluminum sulfate formulated as a styptic pencil. This section allows 
products that meet the criteria established in Sec.  201.66(d)(10) to 
be marketed with reduced labeling.

III. Direct Final Rulemaking

    FDA has determined that the subject of this rulemaking is suitable 
for a direct final rule. This direct final rule revises several older 
labeling warnings and directions for OTC skin protectant astringent 
drug products for consistency with recently issued labeling for OTC 
skin protectant drug products and updates the labeling to the new OTC 
drug labeling format. The actions taken should be noncontroversial, and 
the agency does not anticipate receiving any significant adverse 
comment on this rule.
    If FDA does not receive significant adverse comment by 75 days 
after the date of publication in the Federal Register, the agency will 
publish a document in the Federal Register confirming the effective 
date of the direct final rule. A significant adverse comment is one 
that explains why the rule would be inappropriate, including challenges 
to the rule's underlying premise or approach, or would be ineffective 
or unacceptable without a change. A comment recommending a rule change 
in addition to this rule will not be considered a significant adverse 
comment unless the comment states why this rule would be ineffective 
without the additional change. If timely significant adverse comments 
are received, the agency will publish a notice of significant adverse 
comment in the Federal Register withdrawing this direct final rule.
    Elsewhere in this issue of the Federal Register, FDA is publishing 
a companion proposed rule, identical to the direct final rule, that 
provides a procedural framework within which the proposed rule may be 
finalized in the event the direct final rule is withdrawn because of 
significant adverse comment. The comment period for the direct final 
rule runs concurrently with that of the companion proposed rule. Any 
comments received under the companion proposed rule will be treated as 
comments regarding the direct final rule. Likewise, significant adverse 
comments submitted to the direct final rule will be considered as 
comments to the companion proposed rule and the agency will consider 
such comments in developing a final rule. FDA will not provide 
additional opportunity for comment on the companion proposed rule.
    If a significant adverse comment applies to part of this direct 
final rule and that part may be severed from the remainder of the rule, 
FDA may adopt as final those parts of the rule that are not the subject 
of a significant adverse comment. A full description of FDA's policy on 
the direct final rule procedures may be found in a guidance document 
published in the Federal Register of November 21, 1997 (62 FR 62466).

IV. Analysis of Impacts

    FDA has examined the impacts of the direct final rule under 
Executive Order 12866, 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 has 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 and economic 
analysis before proposing any rule that may result in an expenditure in 
any one year by State, local, and tribal governments, in the aggregate, 
or by the private sector, of $100 million (adjusted annually for 
inflation). The rule that led to the development of this direct final 
rule was published on October 21, 1993, before the Unfunded Mandates 
Reform Act of 1995 was enacted. The agency explains in this direct 
final rule that the direct final rule will not result in an expenditure 
in any one year by State, local, and tribal governments, in the 
aggregate, or by the private sector, of $100 million.
    The agency concludes that this direct final rule is consistent with 
the principles set out in the Executive order and in these two 
statutes. The direct 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. FDA has determined that the direct final rule does 
not have a significant economic impact on a substantial number of small 
entities. The Unfunded Mandates Reform Act does not require FDA to 
prepare a statement of costs and benefits for this final rule, because 
the final rule is not expected to result in any 1-year expenditure that 
would exceed $100 million adjusted for inflation. The current inflation 
adjusted statutory threshold is about $110 million.
    The purpose of this direct final rule is to make some minor 
labeling revisions in the previously issued astringents portion of the 
skin protectant drug products monograph to make the labeling consistent 
with the rest of the monograph and to add small package labeling 
provisions for aluminum sulfate marketed as a styptic pencil.
    Current manufacturers of these products should incur only minor 
costs to relabel their products to meet the monograph. Some 
manufacturers will have to add a warning and revise the directions in 
their labeling. The agency is providing either 24 months from the date 
of publication of this direct final rule or the date of the first major 
labeling revision after the 135-day effective date of this direct final 
rule, whichever occurs first, for the manufacturers to use up existing 
labeling and print new labeling that incorporates the labeling in this 
direct final rule. Further, the labeling in the direct final rule is in 
the new OTC drug labeling format. Therefore, no additional professional 
skills are needed and manufacturers will not incur expenses

[[Page 35293]]

determining how to state the product's labeling.
    The agency believes that relabeling costs of the type required by 
this direct final rule generally average about $2,000 to $3,000 per 
stock keeping unit (SKU) (individual products, packages, and sizes). 
Assuming that there are about 25 affected OTC SKU's in the marketplace, 
total one-time costs of relabeling would be $50,000 to $75,000. The 
agency believes that the actual cost could be lower for the reasons 
stated in the previous paragraph.
    For the reasons stated previously and under the Regulatory 
Flexibility Act (5 U.S.C. 605(b)), the Commissioner certifies that this 
direct final rule will not have a significant economic impact on a 
substantial number of small entities.

V. Paperwork Reduction Act of 1995

    FDA concludes that the labeling requirements 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)).

VI. Environmental Impact

    The agency 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 direct final rule in accordance with the 
principles set forth in Executive Order 13132. FDA has determined that 
the 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, the agency has concluded 
that the rule does not contain policies that have federalism 
implications as defined in the Executive order and, consequently, a 
federalism summary impact statement is not required.

VIII. Comments

    Interested persons may submit to the Dockets Management Branch (see 
ADDRESSES) written or electronic comments regarding this document. 
Submit a single copy of electronic comments to http://www.fda.gov/dockets/ecomments or three hard copies of any written comments, except 
that individuals may submit one hard copy. Comments are to be 
identified with the docket number found in brackets in the heading of 
this document and may be accompanied by a supporting memorandum or 
brief. Received comments may be seen in the Dockets Management Branch 
between 9 a.m. and 4 p.m., Monday through Friday.

List of Subjects in 21 CFR Part 347

    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 part 
347 is amended to read as follows:

PART 347--SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN 
USE

0
1. The authority citation for 21 CFR part 347 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
0
2. Section 347.52 is amended by adding paragraphs (c)(4) and (e) and by 
revising paragraphs (d)(1)(i), (d)(1)(ii), and (d)(3) to read as 
follows:


Sec.  347.52  Labeling of astringent drug products.

* * * * *
    (c) * * *
    (4) For products containing aluminum acetate identified in Sec.  
347.12(a) when labeled for use as a soak, compress, or wet dressing. 
``When using this product [bullet] in some skin conditions, soaking too 
long may overdry''.
    (d) * * *
    (1) * * *--(i) For products used as a soak. ``For use as a soak: 
[bullet] soak affected area for 15 to 30 minutes as needed, or as 
directed by a doctor [bullet] repeat 3 times a day or as directed by a 
doctor [bullet] discard solution after each use''.
    (ii) For products used as a compress or wet dressing. ``For use as 
a compress or wet dressing: [bullet] soak a clean, soft cloth in the 
solution [bullet] apply cloth loosely to affected area for 15 to 30 
minutes [bullet] repeat as needed or as directed by a doctor [bullet] 
discard solution after each use''.
* * * * *
    (3) For products containing witch hazel identified in Sec.  
347.12(c). ``Apply as often as needed''.
    (e) Products formulated and labeled as a styptic pencil and that 
meet the criteria established in Sec.  201.66(d)(10) of this chapter. 
The title, headings, subheadings, and information described in Sec.  
201.66(c) of this chapter shall be printed in accordance with the 
following specifications:
    (1) The labeling shall meet the requirements of Sec.  201.66(c) of 
this chapter except that the headings and information described in 
Sec.  201.66(c)(3) and (c)(7) may be omitted, and the headings, 
subheadings, and information described in Sec.  201.66(c)(4) and (c)(5) 
may be presented as follows:
    (i) The heading and indication required by Sec.  201.66(c)(4) of 
this chapter may be limited to: ``Use [in bold type] stops bleeding of 
minor cuts from shaving''.
    (ii) The ``external use only'' warning in Sec.  347.52(c)(1) and in 
Sec.  201.66(c)(5)(i) of this chapter may be omitted. The second 
warning in Sec.  347.52(c)(1) may state: ``avoid contact with eyes''. 
The warning in Sec.  201.66(c)(5)(x) may be limited to the following: 
``Keep out of reach of children.'' The subheadings in Sec.  
201.66(c)(5)(iii) through (c)(5)(vii) may be omitted, provided the 
information after the heading ``Warning'' contains the warnings in this 
paragraph.
    (2) The labeling shall be printed in accordance with the 
requirements of Sec.  201.66(d) of this chapter except that any 
requirements related to Sec.  201.66(c)(3) and (c)(7), and the 
horizontal barlines and hairlines described in Sec.  201.66(d)(8), may 
be omitted.

    Dated: May 27, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-14818 Filed 6-12-03; 8:45 am]
BILLING CODE 4160-01-SDEPARTMENT OF JUSTICE