
[Federal Register: March 6, 2009 (Volume 74, Number 43)]
[Rules and Regulations]               
[Page 9759-9765]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06mr09-2]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 310 and 347

[Docket No. FDA-1978N-0007] (Formerly Docket No. 78N-021A)
RIN 0910-AF42

 
Astringent Drug Products That Produce Aluminum Acetate; Skin 
Protectant Drug Products for Over-the-Counter Human Use; Technical 
Amendment

AGENCY: Food and Drug Administration, HHS.

[[Page 9760]]


ACTION: Final rule; technical amendment.

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SUMMARY: We (Food and Drug Administration (FDA)) are amending the final 
monograph (FM) for over-the-counter (OTC) skin protectant astringent 
drug products. This amendment clarifies that aluminum acetate 
solutions, produced by dissolving aluminum sulfate tetradecahydrate and 
calcium acetate monohydrate in powder or tablet form in water, are 
generally recognized as safe and effective (GRASE) and not misbranded 
as astringent drug products. The amendment also describes how 
manufacturers should relabel these products to comply with the FM. We 
are issuing this amendment in response to a citizen petition (CP) that 
we received from a manufacturer of OTC astringent drug products. This 
final rule is part of our ongoing review of OTC drug products.

DATES: Effective Date: This regulation is effective March 6, 2009.
    Compliance Date: The compliance date for all products, regardless 
of annual sales, is September 6, 2010.

FOR FURTHER INFORMATION CONTACT: Matthew R. Holman, Center for Drug 
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. What Is the Regulatory History of This Rulemaking?

A. Advance Notice of Proposed Rulemaking (ANPR)

    We published an ANPR for certain OTC skin protectant drug products 
in the Federal Register on September 7, 1982 (47 FR 39436) (the 1982 
ANPR). In the 1982 ANPR, the agency reported that the Advisory Review 
Panel on OTC Miscellaneous External Drug Products (the Panel) 
recommended that we classify solutions containing 2.5 to 5 percent 
aluminum acetate as GRASE for topical use as an astringent. The 1982 
ANPR includes the following terms when referring to this ingredient (47 
FR 39436 at 39444 through 39446):
     ``aluminum acetate''
     ``aluminum acetate solution''
     ``Burow's solution''
    Although some of the aluminum acetate products that the Panel 
evaluated were powders and tablets that were dissolved in water (Refs. 
1 and 2), those products, as manufactured, did not contain aluminum 
acetate. Rather, those powders and tablets contained aluminum sulfate 
and calcium acetate, which produced an aluminum acetate solution when 
dissolved in water.
    In addition, the Panel separately evaluated aluminum sulfate and 
calcium acetate as OTC astringent single active ingredients (i.e., when 
not in combination with each other). The Panel recommended that 
aluminum sulfate, as a single active ingredient, is GRASE and not 
misbranded only for use in a styptic pencil (47 FR 39436 at 39447 and 
39448).\1\ The Panel recommended that calcium acetate be classified as 
not GRASE or misbranded when used as a single active ingredient (47 FR 
39436 at 39444). The Panel was not aware of any data demonstrating the 
safety and effectiveness of calcium acetate, as a single active 
ingredient, when used as an OTC astringent active ingredient in any 
formulation.
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    \1\ In the 1982 ANPR, we stated that the Panel had concluded 
that aluminum sulfate is safe but that there were insufficient data 
to establish its effectiveness for use as a styptic pencil (47 FR 
39436 at 39447 and 39448). In the Federal Register of April 3, 1989 
(54 FR 13490 at 13493), we stated that an apparent administrative 
error had occurred in that the Panel had voted to classify aluminum 
sulfate as GRASE and not misbranded for use in a styptic pencil.
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B. Proposed Rule

    In the Federal Register of April 3, 1989 (54 FR 13490), we 
published a proposed rule amending the tentative final monograph (TFM) 
for OTC skin protectant drug products to include astringent drug 
products (the 1989 TFM). In the 1989 TFM, we proposed monograph status 
for aluminum acetate, as recommended by the Panel (54 FR 13490 at 
13494). However, we revised the Panel's recommended concentration to 
0.13 to 0.5 percent, indicating that the Panel did not take into 
account further dilution of the 2.5 to 5 percent aluminum acetate 
solution (54 FR 13490 at 13494 and 13496). We agreed with the Panel's 
recommendation for calcium acetate and proposed that the ingredient be 
classified as nonmonograph (54 FR 13490 at 13496). We also noted that 
one comment mentioned that the USP (United States Pharmacopeia) 
procedure for preparing Burow's Solution (aluminum acetate solution) de 
novo does not pertain to modified aluminum acetate solutions prepared 
from tablets or powders (54 FR 13490 at 13494).

C. Final Rule

    In the Federal Register of October 21, 1993 (58 FR 54458), we 
published a final rule in the form of a FM for OTC skin protectant drug 
products that established conditions under which OTC astringent drug 
products are GRASE and not misbranded (the 1993 skin protectant FM). 
The 1993 skin protectant FM added GRASE astringent active ingredients 
and labeling for astringents to 21 CFR part 347 subpart A. The 1993 
skin protectant FM, which became effective on October 21, 1994, 
includes 0.13 to 0.5 percent aluminum acetate as an active ingredient 
in Sec.  347.12 (21 CFR 347.12) (then Sec.  347.10(a) (21 CFR 
347.10(a))). The 1993 skin protectant FM specifies that, depending on 
the formulation and concentration of the marketed product, the 
manufacturer must provide adequate directions so that the resulting 
solution to be used by consumers contains 0.13 to 0.5 percent aluminum 
acetate.
    In the 1993 skin protectant FM, we noted that calcium acetate was 
listed in Sec.  310.545(a)(18)(ii) (21 CFR 310.545(a)(18)(ii)) as 
nonmonograph in a final rule published on May 10, 1993 (58 FR 27636 at 
27642).

D. Feedback Letter

    A manufacturer submitted a letter in 1994 requesting clarification 
whether its OTC astringent drug product, a powder containing aluminum 
sulfate and calcium acetate, could continue to be marketed under the 
1993 skin protectant FM (Ref. 3). The manufacturer stated that it 
markets one of the products reviewed by the Panel in which aluminum 
acetate was determined to be GRASE for OTC astringent drug products. 
When dissolved in water according to labeled directions, the 
manufacturer's product becomes an aluminum acetate solution with a 
calcium sulfate precipitate.
    In a 1995 letter to the manufacturer, we stated that the product 
fails to comply with the 1993 skin protectant FM because it contains 
the nonmonograph ingredient calcium acetate (Ref. 4). We suggested that 
the manufacturer contact us to amend the 1993 skin protectant FM to 
allow continued marketing of its product. Subsequently, the 
manufacturer submitted a CP (Ref. 5).

II. Why Is FDA Issuing This Document?

    We are issuing this technical amendment in response to the CP 
submitted by an OTC astringent drug product manufacturer in 1995 (the 
1995 CP) (Ref. 5). The 1995 CP was submitted by a manufacturer who 
marketed one of the products reviewed by the Panel in which aluminum 
acetate was determined to be GRASE for OTC astringent drug products 
(see section I.D of this document). The 1995 CP requested that we 
revise the skin protectant FM (Sec.  347.12(a) (then Sec.  347.10(a)) 
as follows, or in equivalent language having the same effect (Ref. 5): 
``Aluminum acetate, 0.13 to 0.5 percent

[[Page 9761]]

(where the product as marketed consists of salts other than aluminum 
acetate, or where the aluminum acetate concentration of the product as 
marketed is other than 0.13 to 0.5 percent, the manufacturer must 
provide adequate directions so that the resulting solution to be used 
by the consumer consists of 0.13 to 0.5 percent aluminum acetate).'' 
The manufacturer intended ``salts other than aluminum acetate'' to 
include dry formulations of aluminum sulfate plus calcium acetate. The 
manufacturer argued that its labeled directions produce an aluminum 
acetate solution that falls within the concentration range specified in 
the 1993 skin protectant FM.
    We have not taken any enforcement action against these powder and 
tablet products that produce an aluminum acetate solution while 
developing this document as our response to the 1995 CP. In this 
document, we are granting the request in the 1995 CP to revise the 1993 
skin protectant FM by including the combination of aluminum sulfate and 
calcium acetate in powder and tablet dosage forms to prepare an 
aluminum acetate solution.

III. What Changes to the Skin Protectant FM Is FDA Making in This 
Document?

    This document adds the GRASE combination of aluminum sulfate 
tetradecahydrate and calcium acetate monohydrate in powder or tablet 
form to produce a 0.13 to 0.5 percent aluminum acetate solution when 
the powder or tablet is dissolved in the volume of water specified in 
``Directions.'' This technical amendment also includes additional 
labeling requirements for OTC astringent drug products that consist of 
this GRASE combination of active ingredients.
    Since we issued the 1993 skin protectant FM, the United States 
Pharmacopeia/National Formulary (USP/NF) has added monographs for
     Aluminum Sulfate and Calcium Acetate Tablets for Topical 
Solution (Ref. 6) and
     Aluminum Sulfate and Calcium Acetate for Topical Solution 
(Ref. 7).
The second USP monograph is for products formulated as powders. The USP 
monographs state that these products contain aluminum sulfate 
tetradecahydrate and calcium acetate monohydrate, which are the hydrate 
forms of aluminum sulfate and calcium acetate. When a tablet or powder 
containing the aluminum sulfate tetradecahydrate and calcium acetate 
monohydrate is dissolved in water, a chemical reaction occurs that 
produces an aluminum acetate solution and a calcium sulfate 
precipitate.
    Rather than amend the aluminum acetate section of the 1993 skin 
protectant FM as requested in the 1995 CP, we are redesignating 
existing Sec.  347.20(b) as Sec.  347.20(c), and adding a new Sec.  
347.20(b), to include the combination of aluminum sulfate 
tetradecahydrate and calcium acetate monohydrate in powder and tablet 
dosage forms to prepare an aluminum acetate solution. We are limiting 
the combination of ingredients to powder and tablet dosage forms 
because there are corresponding USP monographs for these dosage forms, 
but not for other dosage forms (Refs. 6 and 7). New Sec.  347.20(b) 
states:``Combination of ingredients to prepare an aluminum acetate 
solution. Aluminum sulfate tetradecahydrate may be combined with 
calcium acetate monohydrate in powder or tablet form to provide a 0.13 
to 0.5 percent aluminum acetate solution when the powder or tablet is 
dissolved in the volume of water specified in `Directions'.'' This 
amendment provides an alternate approach to prepare the aluminum 
acetate solution described in Sec.  347.12(a).
    Marketed products have contained varying amounts of aluminum 
sulfate and calcium acetate based on the amount of water in which the 
powder or tablet is dissolved to make an aluminum acetate solution. For 
example, a product with directions to use 16 ounces of water requires a 
larger amount of each ingredient than a product with directions to use 
12 ounces of water. Generally, the products have contained between 53 
and 59 percent aluminum sulfate and 40 to 44 percent calcium acetate in 
each tablet or powder. Inactive ingredients account for the other 
amounts to make 100 percent.
    Because of the varying amount of aluminum sulfate and calcium 
acetate, we are not specifying an amount for each active ingredient 
required in a product. However, this information is required to appear 
in the product's labeling (see 21 U.S.C. 352(e)(1)(A)(ii) and Sec.  
201.66(c)(2) (21 CFR 201.66(c)(2))). Labeling must state the amount of 
each active ingredient in the product and those amounts, when dissolved 
in the amount of water stated in the product's labeling, must produce a 
0.13 to 0.5 percent aluminum acetate solution. We are providing 
labeling in this document to allow manufacturers to continue to market 
these products in this manner.
    We are revising Sec.  347.52 (Labeling of astringent drug products) 
(21 CFR 347.52), which describes specific labeling for products 
containing aluminum sulfate tetradecahydrate and calcium acetate 
monohydrate in powder or tablet dosage forms (see Sample OTC Astringent 
Drug Product Label). ``Aluminum sulfate tetradecahydrate'' and 
``calcium acetate monohydrate'' must appear under the ``Active 
ingredients'' heading in Drug Facts, as is typical for OTC drug 
products. Under the ``Purpose'' heading, an asterisk should follow the 
word ``Astringent''. In addition, a statement explaining the asterisk 
should be included in the ``Active ingredients/Purpose'' section: 
``*When combined together in water, these ingredients form the active 
ingredient aluminum acetate. See Directions.'' The ``Directions'' 
section should include instructions on preparing the aluminum acetate 
solution (0.13 to 0.5 percent) from the powder(s) or tablet(s). These 
directions will inform consumers that a solution is produced by 
dissolving the powder(s) or tablet(s) in water. We believe this 
labeling in the ``Active ingredients/Purpose'' and ``Directions'' 
sections adequately informs consumers that aqueous aluminum acetate is 
acting as the astringent active ingredient.
    The combination product containing aluminum sulfate 
tetradecahydrate and calcium acetate monohydrate has the same 
indications and warnings as other monograph astringent products 
containing aluminum acetate. We are requiring that the ``for use as a 
soak'' and ``for use as a compress or wet dressing'' subheadings in the 
``Directions'' section appear in bold type to make it easier for 
consumers to read and follow the different parts of the directions for 
these products (see Sample OTC Astringent Drug Product Label). For 
consistency in labeling, we are also requiring that the same two 
subheadings in the ``Directions'' section of OTC aluminum acetate 
solution drug products described in Sec.  347.12(a) appear in bold 
type. The information under these subheadings for both types of 
aluminum acetate drug products (i.e., dry and solution formulations) is 
still required to appear in a bulleted format (see Sec.  
347.52(d)(1)(i) and (d)(1)(ii)).
    The following sample OTC astringent drug product label illustrates 
the labeling for products containing aluminum sulfate tetradecahydrate 
and calcium acetate monohydrate in powder or tablet dosage forms to 
produce an aluminum acetate solution:
BILLING CODE 4160-01-S

[[Page 9762]]

[GRAPHIC] [TIFF OMITTED] TR06MR09.000

BILLING CODE 4160-01-C

[[Page 9763]]

This sample label includes the specific labeling required for these 
products in this technical amendment as well as the general labeling 
required by the 1993 skin protectant FM. The format and sequence of the 
information and the font sizes for the title, heading, subheadings, 
text, and other graphic features must be in accordance with Sec.  
201.66.
    In addition to adding new Sec.  347.20(b), we are revising Sec.  
310.545(a)(18)(ii), which currently lists calcium acetate as a 
nonmonograph active ingredient that cannot be included in OTC 
astringent drug products. That section now reads as follows: ``Calcium 
acetate (except calcium acetate monohydrate when combined with aluminum 
sulfate tetradecahydrate to provide an aluminum acetate solution as 
described in Sec.  347.20(b)).'' Therefore, calcium acetate is still 
nonmonograph except in products marketed under new Sec.  347.20(b).
    Because this document adds new Sec.  347.20(b), we are 
redesignating existing Sec.  347.20(b), (c), and (d) as Sec.  
347.20(c), (d), and (e), respectively. We are also revising the 
warnings in 21 CFR 347.50(c) to reflect the Drug Facts format in Sec.  
201.66, while not changing the meaning of these warnings. The Sample 
OTC Astringent Drug Product Label reflects all of these revisions.

IV. Analysis of Impacts

    We have examined the impacts of this final 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). We conclude that this 
final rule is not a significant regulatory action under the Executive 
order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because only a limited number of products will need 
to be relabeled, we certify that this final rule will not have a 
significant economic impact on a substantial number of 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 anticipated 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 $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $130 million, using the most current (2007) Implicit 
Price Deflator for the Gross Domestic Product. We do not expect this 
final rule to result in any 1-year expenditure that would meet or 
exceed this amount.
    The purpose of this final rule is to amend the 1993 skin protectant 
FM to add the combination of aluminum sulfate tetradecahydrate and 
calcium acetate monohydrate for products that include appropriate 
amounts of these ingredients and adequate directions to produce an 
aluminum acetate solution within the monograph concentration range. 
This amendment describes a methodology for manufacturers of these OTC 
astringent drug products to relabel their products and market them in 
compliance with the 1993 skin protectant FM.
    We have identified two OTC skin protectant astringent drug 
products, each with several stockkeeping units (SKUs) (individual 
products, packages, and sizes), that may need to be relabeled. While we 
are aware of several other products that are no longer marketed, there 
may be a few marketed products of which we are not currently aware. 
Accordingly, we estimate that there may be 5 products with 5 to 10 SKUs 
that may be affected by this final rule.
    We have updated the weighted average cost to relabel that we 
estimated for the final rule requiring uniform label formats of OTC 
drug products (64 FR 13254 at 13279 to 13281, March 17, 1999) (i.e., 
$3,600 x 1.164\2\ = $4,190 per SKU). Assuming up to 10 affected OTC 
SKUs in the marketplace, total one-time costs of relabeling could be 
$41,900 (i.e., 10 x $4,190). Because frequent labeling redesigns are a 
recognized cost of doing business in the OTC drug industry, these costs 
may be less. Manufacturers that make voluntary market-driven changes to 
their labeling during the implementation period can implement the 
regulatory requirements for a nominal cost. All products, including 
those with annual sales less than $25,000, will have 18 months 
following publication of the final rule to comply with the 1993 skin 
protectant FM. Therefore, many of the labeling revisions may be done in 
the normal course of business. These steps should help to minimize the 
impact on small entities by providing enough time for implementation to 
enable entities to use up existing labeling stock. In addition, the 
final rule does not require any new reporting or recordkeeping 
activities.
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    \2\ The annual PPI for pulp, paper, and allied products (the 
major cost driver for labeling) rose from 174.1 to 202.6 between 
1998 and 2005 (see http://data.bls.gov/cgi-bin/surveymost). We have 
verified the Web site address, but we are not responsible for 
subsequent changes to the Web site after this document publishes in 
the Federal Register.
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    This final rule also requires manufacturers of the aluminum acetate 
solution products described in Sec.  347.12(a) to make two very minor 
changes in the labeling of their products. They will need to change the 
two ``for use'' subheadings in the directions from standard to bold 
type and should be able to do so at a negligible cost. We estimate that 
less than 10 SKUs will be affected by this minor change. This final 
rule will not impose a significant economic burden on affected 
entities. Therefore, we certify 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)).

V. Paperwork Reduction Act of 1995

    We conclude 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

    We have 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

    We have analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. We have 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

[[Page 9764]]

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 clarifies that OTC 
astringent drug products containing aluminum sulfate tetradecahydrate 
and calcium acetate monohydrate in powder or tablet form for dissolving 
in water to produce an aluminum acetate solution are GRASE and not 
misbranded. The final rule also describes how manufacturers should 
relabel these products to comply with the 1993 skin protectant FM. 
Although this final rule would have a preemptive effect, in that it 
would preclude States from issuing requirements related to these OTC 
astringent 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 
preemption may arise. See Geier v. American Honda Co., 529 U.S. 861 
(2000).
    We believe that the preemptive effect of the final rule would be 
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.'' We 
provided the States with an opportunity for appropriate participation 
in this rulemaking when we sought input from all stakeholders through 
publication of the 1993 skin protectant FM. We received no comments 
from any States on the final rulemaking.
    In addition, on December 17, 2008, FDA's Division of Federal and 
State Relations provided notice via fax and e-mail 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 final rule and encouraged State and local 
governments to review the notice and to provide any comments to the 
docket (Docket No. 1978N-0021A), by a date 30 days from the date of the 
notice (i.e., by January 16, 2009), or to contact certain named 
individuals. We did not receive any comments in response to this 
notice. The notice has been filed in the above-numbered docket.
    In conclusion, we believe that we have complied with all of the 
applicable requirements under the Executive order and have determined 
that the preemptive effects of this rule are consistent with Executive 
Order 13132.

VIII. References

    The following references are on display in the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, Rockville, MD 20852, under Docket No. FDA-1978N-0007 
(formerly Docket No. 1978N-021A) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.
    1. Bluboro product label, Appendix A to CP1.
    2. Domeboro product label.
    3. Letter from S. Buxbaum, Allergan, to R. Heller, FDA, dated 
January 24, 1994, Appendix C to CP1.
    4. Letter from B. Williams, FDA, to T. Mead, Allergan, dated 
January 2, 1995, Appendix D to CP1.
    5. CP1.
    6. The United States Pharmacopeia 31-National Formulary 26, The 
United States Pharmacopeial Convention, Inc., Rockville, MD, pp. 
1360, 2008.
    7. The United States Pharmacopeia 31-National Formulary 26, The 
United States Pharmacopeial Convention, Inc., Rockville, MD, p. 
1359, 2008.

List of Subjects

21 CFR Part 310

    Administrative practice and procedures, Drugs, Labeling, Medical 
devices, Reporting and recordkeeping requirements.

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 parts 
310 and 347 are amended as follows:

PART 310--NEW DRUGS

0
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.

0
2. Section 310.545 is amended by revising the entry for calcium acetate 
in paragraph (a)(18)(ii), by revising paragraph (d) introductory text 
and paragraph (d)(11), and by adding new paragraph (d)(39) to read as 
follows:


Sec.  310.545  Drug products containing certain active ingredients 
offered over-the-counter (OTC) for certain uses.

    (a) * * *
    (18) * * *
    (ii) * * *
* * * * *

Calcium acetate (except calcium acetate monohydrate when combined with 
aluminum sulfate tetradecahydrate to provide an aluminum acetate 
solution as described in Sec.  347.20(b)) of this chapter
* * * * *
    (d) Any OTC drug product that is not in compliance with this 
section is subject to regulatory action if initially introduced or 
initially delivered for introduction into interstate commerce after the 
dates specified in paragraphs (d)(1) through (d)(39) of this section.
* * * * *
    (11) November 10, 1993, for products subject to paragraphs 
(a)(8)(ii), (a)(10)(v) through (a)(10)(vii), (a)(18)(ii) (except 
products that contain ferric subsulfate as covered by paragraph (d)(22) 
of this section and except products that contain calcium acetate 
monohydrate as covered by paragraph (d)(39) of this section) through 
(a)(18)(v)(A), (a)(18)(vi)(A), (a)(22)(ii), (a)(23)(i), (a)(24)(i), and 
(a)(25) of this section.
* * * * *
    (39) September 6, 2010, for products subject to paragraph 
(a)(18)(ii) of this section that contain calcium acetate monohydrate, 
except as provided in Sec.  347.20(b) of this chapter.

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

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


[[Page 9765]]


    Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.

0
4. Section 347.20 is amended by redesignating paragraphs (b), (c), and 
(d) as paragraphs (c), (d), and (e), respectively, and by adding new 
paragraph (b) to read as follows:


Sec.  347.20  Permitted combinations of active ingredients.

* * * * *
    (b) Combination of ingredients to prepare an aluminum acetate 
solution. Aluminum sulfate tetradecahydrate may be combined with 
calcium acetate monohydrate in powder or tablet form to provide a 0.13 
to 0.5 percent aluminum acetate solution when the powder or tablet is 
dissolved in the volume of water specified in ``Directions.''
* * * * *

0
5. Section 347.52 is amended by revising paragraph (a) and (b)(1) 
paragraph heading, and by revising paragraphs (c) and (d)(1), and by 
adding new paragraph (d)(4) to read as follows:


Sec.  347.52  Labeling of astringent drug products.

    (a) Statement of identity. The labeling of the product contains the 
established name of the drug, if any, and identifies the product as an 
``astringent.'' For products containing the combination of aluminum 
sulfate tetradecahydrate and calcium acetate monohydrate identified in 
Sec.  347.20(b), under the ``Purpose'' heading identified in Sec.  
201.66(c)(3) of this chapter, the labeling of each active ingredient in 
the product states ``Astringent*'', which is followed by the statements 
``* When combined together in water, these ingredients form the active 
ingredient aluminum acetate. See [the following in bold italic type] 
Directions.''
    (b) Indications. * * *
    (1) For products containing aluminum acetate identified in Sec.  
347.12(a) or the combination of aluminum sulfate tetradecahydrate and 
calcium acetate monohydrate identified in Sec.  347.20(b). * * *
* * * * *
    (c) Warnings. The labeling of the product contains the following 
warnings under the heading ``Warnings'':
    (1) For all products--(i) The labeling states ``For external use 
only''.
    (ii) The labeling states ``When using this product [bullet] avoid 
contact with eyes. If contact occurs, rinse thoroughly with water.''
    (2) For products containing aluminum acetate identified in Sec.  
347.12(a), witch hazel identified in Sec.  347.12(c), or the 
combination of aluminum sulfate tetradecahydrate and calcium acetate 
monohydrate identified in Sec.  347.20(b). The labeling states ``Stop 
use and ask a doctor if [bullet] condition worsens or symptoms last 
more than 7 days''.
    (3) For products containing aluminum acetate identified in Sec.  
347.12(a) or the combination of aluminum sulfate tetradecahydrate and 
calcium acetate monohydrate identified in Sec.  347.20(b) when labeled 
for use as a compress or wet dressing. The labeling states ``When using 
this product [bullet] do not cover compress or wet dressing with 
plastic to prevent evaporation''.
    (4) For products containing aluminum acetate identified in Sec.  
347.12(a) or the combination of aluminum sulfate tetradecahydrate and 
calcium acetate monohydrate identified in Sec.  347.20(b) when labeled 
for use as a soak, compress, or wet dressing. The labeling states 
``When using this product [bullet] in some skin conditions, soaking too 
long may overdry''.
    (d) Directions. * * *
    (1) For products containing aluminum acetate identified in Sec.  
347.12(a) or the combination of aluminum sulfate tetradecahydrate and 
calcium acetate monohydrate identified in Sec.  347.20(b)--(i) For 
products used as a soak. ``For use as a soak: [preceding words in bold 
type] [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: [preceding words in bold type] [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''.
* * * * *
    (4) For products containing the combination of aluminum sulfate 
tetradecahydrate and calcium acetate monohydrate identified in Sec.  
347.20(b)--(i) For powder dosage form. The labeling states ``[bullet] 
dissolve 1 to 3 packets in [insert volume] of cool or warm water 
[bullet] stir until fully dissolved; do not strain or filter. The 
resulting mixture contains [insert percent] (1 packet), [insert 
percent] (2 packets), or [insert percent] (3 packets) aluminum acetate 
and is ready for use.'' These statements shall be the first statements 
under the heading ``Directions''.
    (ii) For tablet dosage form. The labeling states ``[bullet] 
dissolve 1 to 3 tablets in [insert volume] of cool or warm water 
[bullet] stir until fully dissolved; do not strain or filter. The 
resulting mixture contains [insert percent] (1 tablet), [insert 
percent] (2 tablets), or [insert percent] (3 tablets) aluminum acetate 
and is ready for use.'' These statements shall be the first statements 
under the heading ``Directions''.
* * * * *

    Dated: February 23, 2009.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E9-4746 Filed 3-5-09; 8:45 am]

BILLING CODE 4160-01-S
