[Federal Register Volume 68, Number 114 (Friday, June 13, 2003)]
[Proposed Rules]
[Pages 35346-35348]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-14819]



[[Page 35346]]

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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; Proposed Rule

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend 
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 would revise 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 would add labeling for certain small packages (styptic pencils). 
This action is part of FDA's ongoing review of OTC drug products. This 
proposed rule is a companion document to the direct final rule 
published elsewhere in this issue of the Federal Register.

DATES: Submit written comments on the proposed rule by August 27, 2003.

ADDRESSES: Submit written comments on the proposed 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. In the Federal 
Register of June 4, 2003 (68 FR 33362), FDA published a final rule for 
OTC skin protectant drug products 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 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 proposed rule, the agency is adding this warning, shortening 
the directions for aluminum acetate drug products, and stating 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 proposing to include 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 above 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 proposed 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 proposing to 
add 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

[[Page 35347]]

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 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 proposing to revise 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 
proposing to revise 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 proposing to 
shorten the directions in Sec.  347.52(d)(3) for products containing 
witch hazel to read: ``apply as often as needed''.
    The agency is proposing to add 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. Additional Information

    This proposed rule is a companion to the direct final rule 
published in the final rules section of this issue of the Federal 
Register. This companion proposed rule and the direct final rule are 
identical. This companion proposed rule will provide the procedural 
framework to finalize the rule in the event the direct final rule 
receives significant adverse comments and is withdrawn. The comment 
period for this companion proposed rule runs concurrently with the 
comment period of the direct final rule. Any comments received under 
the companion proposed rule will be treated as comments regarding the 
direct final rule.
    If no significant adverse comment is received in response to the 
direct final rule, no further action will be taken related to this 
proposed rule. Instead, FDA will publish a confirmation document 
stating that the direct final is effective as of 135 days after the 
date of publication in the Federal Register. If FDA receives 
significant adverse comments, the agency will withdraw the direct final 
rule. FDA will proceed to respond to all of the comments received 
regarding the rule and, if appropriate, the rule will be finalized 
under this companion rule using usual notice-and-comment procedures.
    For additional information, see the corresponding direct final rule 
published in the final rules section of this issue of the Federal 
Register. FDA will not provide additional opportunity for comment. 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.

IV. Analysis of Impacts

    FDA has examined the impacts of the proposed 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 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 agency concludes that this proposed rule is consistent with the 
principles set out in the Executive order and in these two statutes. 
The 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. FDA has determined that the proposed 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 proposed rule, because the 
proposed 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 proposed 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 will provide either 24 months from the date 
of publication of a final rule or the date of the first major labeling 
revision after the effective date of the final rule, whichever occurs 
first, for the manufacturers to use up existing labeling and to print 
new labeling that incorporates the labeling included in any final rule 
that may publish based on this proposal. Further, the labeling in the 
proposed rule is in the new OTC drug labeling format. Therefore, no 
additional professional skills are needed and manufacturers will not 
incur expenses determining how to state the product's labeling.
    The agency believes that relabeling costs of the type required by 
this proposed 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 above and under the Regulatory Flexibility 
Act (5 U.S.C. 605(b)), the Commissioner certifies that this proposed 
rule will not have a significant economic impact on a substantial 
number of small entities.

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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. Request for Comments

    This comment period runs concurrently with the comment period for 
the direct final rule; any comments received will be considered as 
comments regarding the direct final rule. 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 forund 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. In the event the direct final rule is withdrawn, all comments 
received will be considered comments on this proposed rule.

List of Subjects in 21 CFR Part 347

    Labeling, Over-the-counter drugs.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that 21 CFR part 347 be amended to read as follows:

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

    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.
    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. 03-14819 Filed 6-12-03; 8:45 am]
BILLING CODE 4160-01-S