[Federal Register: October 15, 2004 (Volume 69, Number 199)]
[Rules and Regulations]
[Page 61148-61150]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr15oc04-4]
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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:
Federal eRulemaking Portal: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.regulations.gov.
Follow the instructions for submitting comments.
Agency Web site: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments.
Follow instructions for submitting comments on the agency Web site.
E-mail: fdadockets@oc.fda.gov. Include Docket No. 1978N-
0064 in the subject line of your e-mail message.
FAX: 301-827-6870.
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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=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:
How often to apply the product,
The effect of bathing or showering before the duration of
effect period ends, and
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