[Federal Register Volume 69, Number 199 (Friday, October 15, 2004)]
[Rules and Regulations]
[Pages 61148-61150]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-23106]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 350

[Docket No. 1978N-0064]
RIN 0910-AC89


Antiperspirant Drug Products for Over-the-Counter Human Use; 
Final Monograph; Partial Stay; Reopening of the Administrative Record

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule; partial stay; reopening of the administrative 
record.

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SUMMARY: The Food and Drug Administration (FDA) is staying part of the 
final monograph (FM) for over-the-counter (OTC) antiperspirant drug 
products that published in the Federal Register on June 9, 2003 (68 FR 
34273). The FM established conditions under which OTC antiperspirant 
drug products are generally recognized as safe and effective (GRASE) 
and not misbranded. This partial stay applies only to the labeling 
claims for enhanced duration in Sec.  350.50(b)(3) and (b)(5) (21 CFR 
350.50(b)(3) and (b)(5)). In addition, FDA is reopening the 
administrative record for the rulemaking on OTC antiperspirant drug 
products to allow for comment and data specifically on the information 
requested in this document. FDA is taking this action in response to a 
citizen petition containing data demonstrating that FDA's effectiveness 
testing guidelines for OTC antiperspirant drug products may support an 
enhanced duration claim greater than 24 hours. This action is part of 
FDA's ongoing review of OTC drug products.

DATES: This rule is effective December 9, 2004. The limitation of the 
enhanced duration claim to 24 hours (21 CFR 350.50(b)(3) and (b)(5)) is 
stayed until further notice.
    Submit written or electronic comments and data by April 13, 2005. 
The administrative record will remain open until April 13, 2005.

ADDRESSES: You may submit comments, identified by Docket No. 1978N-0064 
by any of the following methods:
    <bullet> Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.
    <bullet> Agency Web site: http://www.fda.gov/dockets/ecomments. 
Follow instructions for submitting comments on the agency Web site.
    <bullet> E-mail: <a href="/cdn-cgi/l/email-protection#b7d1d3d6d3d8d4dcd2c3c4f7d8d499d1d3d699d0d8c1"><span class="__cf_email__" data-cfemail="7e181a1f1a111d151b0a0d3e111d50181a1f50191108">[email protected]</span></a>. Include Docket No. 1978N-
0064 in the subject line of your e-mail message.
    <bullet> FAX: 301-827-6870.
    <bullet> Mail/Hand delivery/Courier [For paper, disk, or CD-ROM 
submissions]: Division of Dockets Management, 5630 Fishers Lane, rm. 
1061, Rockville, MD 20852.
    Instructions: All submissions received must include the agency name 
and Docket No. 1978N-0064. All comments received will be posted without 
change to http://www.fda.gov/dockets/ecomments, including any personal 
information provided. For detailed instructions on submitting comments 
and additional information on the rulemaking process, see the 
``Comments'' heading of the SUPPLEMENTARY INFORMATION section of this 
document.
    Docket: For access to the docket to read background documents or 
comments received, go to http://www.fda.gov/dockets/ecomments and/or 
the Division of Dockets Management, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Xin Zhou, Center for Drug Evaluation 
and Research (HFD-560), Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857, 301-827-2222.

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of October 10, 1978 (43 FR 46694), FDA 
published an advance notice of proposed rulemaking (ANPRM) to establish 
a monograph for OTC antiperspirant drug products, together with the 
recommendations of the Advisory Review Panel on OTC Antiperspirant Drug 
Products (the Panel), which evaluated the data on these products. The 
Panel classified claims for enhanced duration of effect as Category III 
(more data needed) because the Panel did not receive any scientific 
data to support a claim of prolonged or enhanced duration of effect (43 
FR 46694 at 46728).
    In the Federal Register of August 20, 1982 (47 FR 36492), FDA 
issued a proposed rulemaking or tentative final monograph (TFM) for OTC 
antiperspirant drug products. To standardize the antiperspirant drug 
product effectiveness test, FDA also issued guidelines for 
effectiveness testing of antiperspirant drug products (47 FR 36492 at 
36504). However, FDA did not include testing recommendations for an 
enhanced duration claim in these guidelines because the Panel had not 
recommended such guidelines and FDA

[[Page 61149]]

received no comments on this subject in response to publication of the 
ANPRM.
    In response to the TFM, FDA received data from 15 studies to 
support enhanced duration claims. FDA found the studies supportive of a 
24-hour or all day protection claim and included such a claim in Sec.  
350.50(b)(3) and (b)(5) of the FM. However, FDA stated that claims of 
enhanced duration for more than 24 hours are nonmonograph because FDA 
had not received any data to demonstrate antiperspirant effectiveness 
for more than 24 hours according to the Panel's criteria (68 FR 34273 
at 34278).

II. Partial Stay of Part 350

    Following publication of the antiperspirant FM, a drug manufacturer 
and an association representing manufacturers submitted citizen 
petitions disagreeing with FDA's decision to limit the enhanced 
duration claim to 24 hours (Refs. 1 and 2). Neither petition contained 
any effectiveness testing data to support enhanced duration claims 
beyond 24 hours. However, the manufacturer subsequently submitted such 
data from two studies (Ref. 3).
    FDA evaluated the data and the results demonstrate that a roll-on 
and a solid stick antiperspirant drug product are extra effective for 
48 hours duration (i.e., sweat was reduced by at least 30 percent in 
the majority of subjects up to 48 hours after antiperspirant 
application). The protocol in the two studies followed FDA's testing 
guidelines, with no significant deviations from those guidelines. The 
antiperspirant drug products used in the studies contained an active 
ingredient at a concentration allowed under the antiperspirant FM 
(Sec.  350.10 (21 CFR 350.10)). Thus, FDA believes the study results 
suggest that FDA's testing guidelines can be used to test enhanced 
duration claims of up to 48 hours. Accordingly, FDA is staying the 
enhanced duration claim limitation of 24 hours (in Sec.  350.50(b)(3) 
and (b)(5)) so that products labeled for enhanced duration claims 
greater than 24 hours and up to 48 hours can continue to be marketed 
while FDA reviews additional data on such claims. Manufacturers making 
such claims for their products should have supporting test data in 
their files. FDA will consider allowing enhanced duration claims of 
greater than 48 hours after it receives and evaluates data supporting 
such claims. This stay will remain in effect until further 
documentation is provided in a future issue of the Federal Register.
    To the extent that 5 U.S.C. 553 applies to this action, it is 
exempt from notice and comment because it constitutes a rule of 
procedure under 5 U.S.C. 553(b)(3)(A). Alternatively, FDAs 
implementation of this action without opportunity for public comment 
comes within the good cause exceptions in 5 U.S.C. 553(b)(3)(B) and 
(d)(3) in that obtaining public comment is impracticable, unnecessary, 
and contrary to the public interest. FDA is staying the enhanced 
duration claim limitation of 24 hours in Sec.  350.50(b)(3) and (b)(5) 
because FDA received and is reviewing data demonstrating an enhanced 
duration claim greater than 24 hours. FDA is also reopening the 
administrative record and inviting the submission of additional 
comments and data related to the effectiveness of antiperspirant drug 
products for more than 24 hours. Following evaluation of submitted 
comments and data, FDA will propose amendments to Sec.  350.50(b)(3) 
and (b)(5) and possibly other sections of part 350. Thus, there will be 
an opportunity for public comment on enhanced duration claims greater 
than 24 hours within proposed amendments to part 350. In this final 
rule, FDA is providing an opportunity for comment on whether this 
partial stay should be modified or revoked.

III. Information Requested

    In the antiperspirant FM, FDA stated that claims of enhanced 
duration for more than 24 hours are nonmonograph because FDA did not 
receive any data to demonstrate antiperspirant effectiveness for more 
than 24 hours (68 FR 34273 at 34278). Because FDA has now received data 
demonstrating antiperspirant product effectiveness for 48 hours, FDA is 
reopening the administrative record to provide for additional 
submission of data and comments on enhanced duration effectiveness 
claims for antiperspirant drug products. FDA would like to evaluate 
additional data demonstrating antiperspirant effectiveness beyond 24 
hours before including enhanced duration claims for longer time periods 
(e.g., 48 hours) in the FM. FDA will only include enhanced duration 
claims in the FM for time periods for which appropriate data have been 
submitted to demonstrate effectiveness.

A. Testing Conditions

    To determine whether enhanced duration claims of effectiveness 
beyond 24 hours are GRASE, FDA strongly encourages manufacturers to 
submit data that meet the following six conditions. First, studies 
should be conducted according to the testing guidelines referenced in 
21 CFR 350.60, which are on file in the Division of Dockets Management 
(see ADDRESSES). These guidelines are available at http://www.fda.gov/cder/otc/index.htm.
    Second, studies should be conducted using antiperspirant drug 
products that contain active ingredients listed in Sec.  350.10. The 
test product ingredient and strength must be identified in the data 
submitted to FDA.
    Third, FDA encourages interested parties to conduct enhanced 
duration effectiveness tests using different active ingredients and 
dosage forms. These data will demonstrate that enhanced duration claims 
determined by the testing guidelines are applicable to multiple active 
ingredient and dosage forms. Fourth, FDA would like data submitted from 
different testing laboratories. Ideally, the same antiperspirant drug 
product will be tested at multiple laboratories, to validate the 
reproducibility of the testing results.
    Fifth, FDA believes that the test subject panel composition should 
reflect consumer demographics (Ref. 4) although the testing guidelines 
do not specify the panel composition. Although the testing guidelines 
do not specify the panel composition, FDA would like data from roughly 
equal numbers of men and women. It would also be informative if 
submitted studies also identified race or ethnicity of subjects. FDA 
would like to assure that the submitted study results demonstrate 
enhanced duration of effectiveness for the entire consumer population, 
not just a subset of the population.
    Sixth, FDA is interested in reviewing data for antiperspirant drug 
products with standard effectiveness as well as products with extra 
effectiveness. FDA would like to determine whether enhanced duration 
claims are limited to extra effective antiperspirant drug products or 
whether enhanced duration claims also apply to standard (effectiveness) 
antiperspirant drug products.

B. Labeling Questions

    In addition to data demonstrating an enhanced duration claim beyond 
24 hours, FDA requests comments on labeling related to products having 
such a claim. Currently, products demonstrating enhanced duration are 
allowed to contain a statement such as ``last 24 hours'' (Sec.  
350.50(b)(3) and (b)(5)) to inform consumers about the duration of 
effectiveness. However, there are no specific direction statements 
about how frequently to apply the product. The directions in Sec.  
350.50(d) simply state ``apply to underarms only.'' For products 
demonstrating effectiveness for greater

[[Page 61150]]

than 24 hours (one day), additional or alternative labeling may be 
necessary. FDA would like comments regarding labeling, such as the 
following:
    <bullet> How often to apply the product,
    <bullet> The effect of bathing or showering before the duration of 
effect period ends, and
    <bullet> Whether any other special labeling should apply to 
products with a duration of effect greater than 24 hours.
    FDA also requests comments on whether there should be any limit on 
the enhanced duration claim and whether there are any potential safety 
issues if a product with enhanced duration of action is reapplied more 
frequently than directed (e.g., an antiperspirant labeled as providing 
48 hours of sweat protection applied every 24 hours).

IV. Analysis of Impacts

    The economic impact of the FM was discussed in the final rule (68 
FR 34273 at 34289). This partial stay of the labeling claims for 
enhanced duration in Sec.  350.50(b)(3) and (b)(5) does not change the 
economic impact on industry described in the final rule.
    FDA has examined the impacts of this 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 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 requires 
that agencies prepare a written statement of anticipated costs and 
benefits 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 current inflation adjusted statutory threshold is about 
$110 million.
    FDA concludes that this final rule is consistent with the 
regulatory philosophy and principles identified in the Executive order 
and in these two statutes. The 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 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 this final rule is not expected to result in 
any 1-year expenditure that would exceed $100 million adjusted for 
inflation.
    The purpose of this final rule is to stay the effective date of one 
part of the antiperspirant FM: The limitation of the enhanced duration 
claim to 24 hours (Sec.  350.50(b)(3) and (b)(5)). The partial stay 
will allow manufacturers who have supporting data to include greater 
than 24 hour duration claims in the labeling of OTC antiperspirant drug 
products while FDA evaluates data to support such claims using FDA's 
effectiveness test. FDA has learned that one manufacturer has 
approximately 40 stockkeeping units (SKUs) and another manufacturer has 
several SKUs with labels indicating effectiveness for more than 24 
hours. These manufacturers will not have to revise the existing 
``enhanced duration'' portion of their labeling when the FM becomes 
effective on December 9, 2004. Accordingly, FDA certifies that this 
final rule will not have a significant economic impact on a substantial 
number of small entities. Therefore, under the Regulatory Flexibility 
Act, no further analysis is required.

V. Paperwork Reduction

    This final rule contains no collections of information. Therefore, 
clearance by the Office of Management and Budget under the Paperwork 
Reduction Act of 1995 is not required.

VI. 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.

VII. Federalism

    FDA has analyzed this 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, FDA 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. Request for Comments

    Interested persons may submit written or electronic comments 
regarding this rule to the Division of Dockets Management (see 
ADDRESSES). Three copies of all written comments are to be submitted. 
Individuals submitting written comments or anyone submitting electronic 
comments may submit one 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 Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday.

IX. References

    The following references are on display in the Division of Dockets 
Management (see ADDRESSES) under Docket No. 1978N-0064 and may be seen 
by interested persons between 9 a.m. and 4 p.m., Monday through Friday.

    1. Comment No. PRC1.
    2. Comment No. PRC2.
    3. Comment No. SUP4.
    4. Comment No. C54.

X. Authority

    This final rule (partial stay) is issued under sections 201, 501, 
502, 503, 505, 510, and 701 of the Federal Food, Drug, and Cosmetic Act 
(21 U.S.C. 321, 351, 352, 353, 355, 360, and 371) and under authority 
delegated to the Commissioner of Food and Drugs.

    Dated: October 6, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-23106 Filed 10-14-04; 8:45 am]
BILLING CODE 4160-01-S


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