[Federal Register Volume 76, Number 46 (Wednesday, March 9, 2011)]
[Proposed Rules]
[Pages 12916-12920]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-5145]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 310
[Docket No. FDA-1981-N-0012] (Formerly Docket No. 1981N-0022)
RIN 0910-AF45
Benzocaine; Weight Control Drug Products for Over-the-Counter
Human Use
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is issuing a proposed
rule to reclassify benzocaine from its previously proposed monograph
status (category I) for over-the-counter (OTC) weight control use to
nonmonograph status. Although, in the Federal Register of February 26,
1982, an advanced notice of proposed rulemaking (ANPR) included the
recommendation of an Advisory Panel, consisting of health care
providers from outside FDA, recommended that benzocaine should be
generally recognized as safe and effective (GRASE) for weight control,
this document includes our first evaluation of benzocaine for this use.
Based on our evaluation of the available data and information, we have
tentatively concluded that the data are not sufficient to support the
safety and effectiveness of benzocaine for this use. This proposed
rule, if finalized, would require an approved new drug application
(NDA) or abbreviated new drug application (ANDA) for the marketing of
OTC weight control products containing benzocaine.
DATES: Submit written or electronic comments on the proposed rule by
June 7, 2011. See section IX of this document for information on the
proposed effective date of this proposed rule.
ADDRESSES: You may submit comments, identified by Docket No. FDA-1981-
N-0012 (formerly Docket No. 1981N-0022 and RIN No. 0910-AF45 by any of
the following methods:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
Written Submissions
Submit written submissions in the following ways:
FAX: 301-827-6870.
Mail/Hand delivery/Courier (for paper, disk, or CD-ROM
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
Instructions: All submissions received must include the Agency name
and Docket No. FDA-1981-N-0012 (formerly Docket No. 1981N-0022) and RIN
No. 0910-AF45 for this rulemaking. All comments received may be posted
without change to http://www.regulations.gov, including any personal
information provided.
Docket: For access to the docket to read background documents or
comments received, go to http://www.regulations.gov and insert the
docket number, found in brackets in the heading of this document, into
the ``Search'' box and follow the prompts and/or go to the Division of
Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Michelle M. Jackson, Center for Drug
Evaluation and Research (HFD-560), Food and Drug Administration, 10903
New Hampshire Ave., Bldg. 22, MS 5411, Silver Spring, MD 20993-0002,
301-796-2090.
SUPPLEMENTARY INFORMATION:
I. Purpose of This Document
In the Federal Register of February 26, 1982, we (FDA) published an
ANPR to establish a monograph for OTC weight control drug products. The
ANPR included the recommendations of an Advisory Review Panel on the
OTC Miscellaneous Internal Drug Products (the Panel) that evaluated all
OTC weight control drug products on the market at the time the OTC drug
review began in 1972. The Panel consisted of
[[Page 12917]]
scientists and health care providers from outside FDA. The Panel
concluded that ``benzocaine is safe for oral use as an OTC anorectic in
a dose of 3 to 15 milligrams (mg) in gum, lozenges, or candy'' and that
``benzocaine in the form of gum, lozenges, or candy is an effective OTC
drug product for weight control'' (47 FR 8466 at 8474). The Panel
believed that benzocaine numbed the oral cavity (including the taste
buds), thereby discouraging food consumption and decreasing caloric
intake.
We reviewed the information and data available to the Panel as well
as information and data that has been developed since the Panel met to
help us determine whether benzocaine is GRASE when used in OTC weight
control drug products. Under the Federal Food, Drug, and Cosmetic Act
(the FD&C Act), all ``new drugs'' are required to obtain approval under
section 505 of the FD&C Act (21 U.S.C. 355) prior to marketing. Most
drugs are ``new drugs'' under the FD&C Act; however, a drug is excluded
from being a ``new drug'' (and therefore is not required to obtain
approval under section 505) if it is ``generally recognized, among
experts qualified by scientific training and experience to evaluate the
safety and effectiveness of drugs, as safe and effective for use under
the conditions prescribed, recommended, or suggested in the labeling
thereof.'' (21 U.S.C. 321(p)(1)).\1\
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\1\ Consistent with the principles explained previously, the OTC
drug review regulations in 21 CFR 330.10 specify the considerations
and evidence required to establish both safety and effectiveness.
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As explained in this document, we tentatively conclude that the
existing evidence is inadequate to establish that OTC weight control
drug products containing benzocaine are GRASE. Accordingly, we are
proposing to classify benzocaine as nonmonograph (i.e., not GRASE) for
use in OTC weight control drug products. If this proposed rule becomes
a final rule, OTC weight control drug products containing benzocaine
will require an approved NDA or ANDA. Studies that may help demonstrate
the safety and effectiveness of weight loss drug products are described
in an FDA guidance entitled ``Developing Products for Weight
Management'' (Ref. 1).
II. Rulemakings and Petitions for OTC Weight Control Drug Products
The Panel responsible for evaluating OTC weight control drug
products recommended that benzocaine-containing drug products be deemed
GRASE for use in OTC weight control drug products. The Panel's
recommendations were published in the Federal Register as an ANPR for
OTC weight control products in 1982 (47 FR 8466).
Following publication of the 1982 ANPR, Thompson Medical Co., a
manufacturer of OTC weight control drug products, submitted two citizen
petitions, one in 1990 and another in 1992, to support the
effectiveness of benzocaine for use as an appetite suppressant (Refs. 2
and 3). The 1990 petition (Ref. 2) included a clinical study by Collipp
(Refs. 4 and 5) and a summary of a clinical study by Piscano and
Lichter (Ref. 6) as data supporting the effectiveness of benzocaine as
an appetite suppressant. We responded to the manufacturer's 1990
petition (Ref. 7) reviewing the data submitted in the petition and
explaining our finding that the data did not provide substantial
evidence from adequate and well-controlled studies to support the
effectiveness of benzocaine for weight control use.
The 1992 petition (Ref. 3) was submitted in response to our 1991
letter. The petition provided two unpublished statistical reevaluations
of the Collipp study, arguing that this data supported finding
benzocaine GRASE for use in OTC weight control drug products. We
responded to the petition in 1993 (Ref. 8), stating that the
reevaluations of the Collipp study did not substantiate the claim of
effectiveness of benzocaine for use in weight control. The two
reanalyses of the Collipp data include: (1) An analysis of covariance
excluding subjects that failed to meet either the age or the degree of
overweight inclusion criteria, and (2) a hierarchical regression model
to determine the effect of benzocaine after attempting to control for
any familial effects. Neither of these analyses adequately addressed
the three main problems that were listed in the 1991 response: (1)
Possible breaking of the blind; (2) imbalance in the sample for
important variables (age by family status); and (3) lack of
randomization within families, affecting the independence of
observations. These problems potentially biased the data affecting the
interpretability of the study results.
Subsequent to our letter, we received draft protocols for
effectiveness studies (Ref. 9) from the same manufacturer, which were
intended to generate support for a GRASE finding. We sent
recommendations on the draft protocols in 1992 (Ref. 10), but have not
yet received any study results.
III. Efficacy Evaluation
We are proposing that benzocaine be classified as nonmonograph at
any concentration for use in OTC weight control drug products. This
conclusion is based in part on our review of the effectiveness data
that was submitted to the Panel (Refs. 11 through 17) and additional
data submitted to us after publication of the 1982 ANPR, including the
two petitions and draft protocols described previously (Refs. 2, 3, and
9). In our responses to the petitions, we explained in detail why we
did not find the available data adequate to support a determination
that benzocaine is generally recognized as effective (GRAE) for this
use (Refs. 7, 8, and 10). In this document, we summarize the available
data and limitations that prevent us from finding benzocaine GRAE for
use in OTC weight control drug products. We have not received any
additional data from any company or citizen since our 1992 response
letter (Ref. 10) discussed previously; and we are not aware of any
safety or effectiveness studies for benzocaine in OTC weight control
drug products conducted since 1992.
In the following sections, we will first describe the studies
reviewed by the Panel. After reviewing the data and findings from these
studies, we will explain why the Agency has concluded that these
studies do not support a finding that benzocaine is GRAE for use in OTC
weight control drug products.
A. Non-Clinical Studies
1. Review of Studies
In the ANPR, we reported that the Panel considered a few
nonclinical studies (Refs. 11, 12, and 13) on benzocaine for weight
control. One of the factors involved in overeating and resulting
obesity is the need to satisfy the sense of taste. Horowitze (Ref. 11)
and Rosner (Ref. 12) showed that there appears to be a decreased
ability to detect degrees of sweetness by taste perception after
chewing gum containing benzocaine. Coons (Ref. 13) demonstrated the
effects of a local anesthetic on hunger reduction in rats. The Panel
considered this study to be an objective demonstration of the
effectiveness of a local anesthetic on hunger reduction.
2. Analysis of Studies
We do not believe these studies support a GRAE determination
because they do not demonstrate that decreased taste perception or
decreased hunger results in weight loss. To find benzocaine GRAE based
in part on these types of studies, we would also need data
demonstrating what level of decrease in taste perception or hunger
actually resulted in a ``clinically
[[Page 12918]]
significant benefit of the type claimed'' (i.e., weight loss) as
required under Sec. 330.10(a)(4)(ii) (21 CFR 330.10(a)(4)(ii)).
B. Clinical Studies
1. Review of Studies
The Panel also considered clinical studies that included weight
loss as an endpoint. Gould (Refs. 14 and 15) assessed various case
reports citing 1.5 to 2.0 pounds (lbs) per week weight loss using
lozenges containing benzocaine and essential oils in conjunction with
dietary restrictions. Plotz (Ref. 16) conducted an uncontrolled, non-
randomized 10-week study of 50 overweight adults (12 to 102 lbs
overweight). The subjects were instructed to chew one or two pieces of
gum for 5 or 10 minutes followed by a glass of water, just before
meals. If subjects became hungry between meals, they could chew gum
every few hours. The study results showed weight loss (2 pounds per
week) in 45 of 50 patients using the benzocaine gum in conjunction with
dietary restrictions.
McClure and Brush (Ref. 17) conducted a placebo-controlled,
randomized, double-blinded 21-week study of 308 overweight adults (255
females and 53 males). The subjects were divided into five paired
treatment groups:
Group 1: Dextroamphetamine sulfate (10 mg, daily)
Group 2: OTC proprietary appetite suppressant (AYDS)
Group 3: Dietary restriction (800 to 1,200 calories daily)
Group 4: Glucose hard candy containing benzocaine,
caffeine, and vitamins (benzocaine group)
Group 5: Glucose candy only (control group)
Over the course of 4 weeks, 170 participants dropped out of the
study (37 participants from the dextroamphetamine group, 43
participants from the AYDS group, 51 participants from the dietary
restriction group, 9 participants from the benzocaine group, and 30
participants from the control group). The investigators reported an
average weight loss during the first 4 weeks of 4.6 lbs for the glucose
(control) group and 12.1 lbs for the benzocaine group. After 21 weeks,
the control group lost a weekly average of 0.60 lbs as compared to 2.20
lbs for the benzocaine group.
In addition to these studies reviewed by the Panel, as described
previously, we also reviewed clinical studies submitted by a
manufacturer of OTC weight control drug products in two petitions. The
studies provided in the petitions included weight loss as an endpoint.
Reports purporting to be two studies by Collipp (one published and one
unpublished) were submitted. These reports appear to be the same study
(Refs. 4 and 5). The Collipp study was designed to be a 6-week, double-
blind, placebo-controlled, randomized trial comparing benzocaine (5 mg)
lozenges with placebo lozenges that were identical in appearance (Ref.
4). Male or female subjects who weighed 15 to 30 percent more than the
ideal weight for their body frame as determined from Metropolitan Life
Insurance Co. weight tables and were between 14 and 55 years of age
were eligible for enrollment. Subjects were recruited from the same
families. Subjects were instructed to follow a 1,250 calorie diet and
to take 1 to 2 lozenges 10 minutes before meals, 1 lozenge instead of
dessert, and 1 or 2 lozenges between meals. Subjects were also
instructed to drink a glass of water, tea, coffee, or other non-caloric
beverage with each lozenge ingestion. Body weight was measured at week
0 and biweekly for the next 6 weeks. Subjects were also asked to rate
the average quality of between-meal appetite suppression as mild,
moderate, or complete.
The study results showed that the mean body weight decreased from
week 0 in both the active treatment and placebo groups. Subjects
treated with benzocaine had a mean weight loss that was statistically
significant (p <=: 0.001) at all time points. The mean weight loss
during the study was approximately twice as great for subjects treated
with benzocaine (-3.5, -4.9, and -6.0 at 2, 4, and 6 weeks,
respectively) compared to placebo (-2.1, -2.9, and -2.7 at 2, 4, and 6
weeks, respectively). The manufacturer also submitted a study by
Piscano and Lichter (Ref. 6) which consisted of a 1-page summary
describing an 8-week uncontrolled trial involving 26 children. The
summary listed the baseline weight, final weight, and weight loss of
each subject. The summary results showed that the subjects lost
approximately 0.5 lbs/week. There was no protocol description and no
statistical analysis.
2. Analysis of Studies
We found a lack of substantial evidence consisting of adequate and
well-controlled studies, as required in Sec. 330.10(a)(4)(ii), on
which to base a determination of the effectiveness of benzocaine in OTC
weight control drug products. In general, the clinical studies reviewed
by the Panel (Refs. 14 through 17) are inadequately controlled, and
study results were not clinically and statistically significant. For
example, among other limitations, the Gould studies (Refs. 14 and 15)
were not well-controlled, as these studies consisted of case reports.
Similarly, the Plotz study (Ref. 16) was not well controlled, being
both uncontrolled and non-randomized. Finally, as detailed in our 1993
response (Ref. 8), the McClure and Brusch study (Ref. 17) had
significant methodological flaws including potential issues with
subject recruitment, inconsistent follow up of subjects and inadequate
assessment of baseline characteristics.
The materials submitted in the petition were also insufficient to
establish the effectiveness of benzocaine in OTC weight control
products. For example, the Pisano and Lichter (Ref. 6) study was not
adequate and well-controlled as it consisted of case reports, did not
include a protocol description and did not provide a statistical
analysis. Similarly, the Collipp study and the reevaluations of the
study submitted in the petitions do not provide detail regarding study
design and outcomes sufficient to show benzocaine is GRASE for use in
weight control. Specifically, the Collipp study had a significant
number of limitations that prevent us from concluding that benzocaine
is GRAE for weight control:
Non-random selection of subjects
Possible breaking of blinding
Analysis did not account for a lack of independence among
subjects within the same family, potentially affecting the study's
findings
It is important to note that after providing the petitioning
manufacturer with a response describing these limitations, we received
a protocol for a further study from the manufacturer (Ref. 9). We
provided feedback on the protocol in 1992 (Ref. 10), but we have not
yet received the study results from the manufacturer. In order to
establish effectiveness, additional data are still needed to show that
benzocaine causes a clinically and statistically significant weight
loss when compared with placebo. The industry is advised to consult a
recently published FDA guidance on the development of products for
weight management about the requirement of clinical data (Ref. 1).
IV. Safety Evaluation
We are not aware of adequate data to demonstrate that OTC weight
control drug products containing benzocaine are generally recognized as
safe (GRAS) as defined under Sec. 330.10(a)(4)(ii). Under this
regulatory provision, support for a GRAS showing ``shall consist of
adequate tests by methods reasonably applicable to show the drug is
safe under the prescribed, recommended, or suggested conditions of
use.'' We believe
[[Page 12919]]
that the safety of the Panel's proposed benzocaine dosing for OTC
weight control use (multiple 3 to 15 mg doses for up to 3 months) has
not been adequately established. Additional safety data is needed to
establish dosage limitations or other aspects of the labeling. Our
current recommendation as to what would constitute adequate testing for
a weight control drug product is described in our guidance on weight
control drug products (Ref. 1).
V. Analysis of Impacts
We have examined the impacts of this proposed 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 believe that this
proposed rule is not a significant regulatory action as defined by 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 few products will likely be affected and
those effects would probably be small, we do not believe that this
proposed rule would 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 $135 million, using the most current (2009) Implicit
Price Deflator for the Gross Domestic Product. We do not expect this
proposed rule to result in any 1-year expenditure that would meet or
exceed this amount.
If this proposed rule is finalized, OTC marketing of weight control
drug products containing benzocaine for this use will cease, unless a
product is approved under an NDA or ANDA. In this proposed rule, we
tentatively conclude that OTC weight control drug products containing
benzocaine lack sufficient evidence to support a finding that such
products are GRASE, and that finalization of the regulatory status of
this ingredient will benefit consumers by removing from the marketplace
products that have not been shown to be safe and effective. We do not
expect this rule to have a significant effect on industry as a whole,
as we have only been able to identify one company that manufactures a
benzocaine-containing OTC weight control drug product.
We have few alternatives available to us when we determine there
are no data available to demonstrate that an active ingredient is
GRASE. Even without evidence of harm caused by the use of these
products, they cannot remain on the market because there is no evidence
that they are safe and effective. Accordingly, we have proposed a 30-
day period within which companies may remove benzocaine-containing
weight control drug products from the market. We believe the only
alternative to this approach is a longer implementation period.\2\ We
could allow a longer implementation period so manufacturers would have
time to submit additional effectiveness and safety data, but if we took
this approach, consumers would be unnecessarily exposed to products
that have not been shown to be effective or safe.
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\2\ See 5 U.S.C. 553(d).
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VI. Paperwork Reduction Act of 1995
This proposed 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.
VII. 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.
VIII. Federalism
We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. 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 intended preemption of State law, or where the exercise of
State authority conflicts with the exercise of Federal authority under
the Federal statute.'' The sole statutory provision giving preemptive
effect to the proposed rule is section 751 of the act (21 U.S.C. 379r).
We believe that the preemptive effect of this proposed rule, if
finalized, would be consistent with Executive Order 13132. Through the
publication of this proposed rule, we are providing notice and an
opportunity for State and local officials to comment on this
rulemaking.
IX. Proposed Effective Date
Due to effectiveness concerns discussed in this document, any final
rule based on this proposal would become effective 30 days after the
date of its publication. Manufacturers are urged to comply voluntarily
with this proposed rule and to cease OTC marketing at the earliest
possible date.
X. References
The following references have been placed on display in the
Division of Dockets Management (see ADDRESSES) under Docket No. FDA-
1981-N-0012 (formerly 1981N-0022) and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday through Friday. (FDA has verified the
Web site address, but we are not responsible for any subsequent changes
to the Web site after this document publishes in the Federal Register.)
1. FDA, ``Draft Guidance for Industry--Developing Products for
Weight Management,'' February 2007, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071612.pdf, accessed on August 27, 2010.
2. Comment No. CP12, Docket No. FDA-1981-N-0012 (formerly 1981N-
0022), Division of Dockets Management System.
3. Comment No. CP15, Docket No. FDA-1981-N-0012 (formerly 1981N-
0022), Division of Dockets Management System.
4. Collipp, P. J., ``The Treatment of Exogenous Obesity by Medicated
Benzocaine Candy: A Double-Blind Placebo-Controlled Study,'' in OTC
Vol. 170010, Docket No. FDA-1981-N-0012 (formerly 1981N-0022),
Division of Dockets Management.
5. Collipp, P. J., ``The Treatment of Exogenous Obesity by Medicated
Benzocaine Candy: A Double Blind Placebo Study,'' Obesity/Bariatric
Medicine, 10:123-125, 1981.
6. Piscano, J. and H. Lichter, ``A Matter of Taste,'' Fredrick Fell
Publishers, Inc., New York, New York, pp. 42-64, 1979.
7. Comment No. LET82, Docket No. FDA-1981-N-0012 (formerly 1981N-
0022), Division of Dockets Management System.
8. Comment No. LET87, Docket No. FDA-1981-N-0012 (formerly 1981N-
0022), Division of Dockets Management System.
9. Comment No. PR9, Docket No. FDA-1981-N-0012 (formerly 1981N-
0022), Division of Dockets Management System.
10. Comment No. LET84, Docket No. FDA-1981-N-0012 (formerly 1981N-
0022), Division of Dockets Management System.
[[Page 12920]]
11. Horowitz, S. and R. P. Scalici, ``Results of Sensory Panel Tests
on Slim-Mint Chewing Gum,'' in OTC Vol. 170010, Docket No. FDA-1981-
N-0012 (formerly 1981N-0022), Division of Dockets Management.
12. Rosner, L., ``To Determine the Effect of Chewing Slim-Mint Gum
Upon Taste Perception, Particularly Toward Sweetness,'' in OTC Vol.
170010, Docket No. FDA-1981-N-0012 (formerly 1981N-0022), Division
of Dockets Management.
13. Summary Minutes of the 11th meeting of the Advisory Review Panel
on OTC Miscellaneous Internal Drug Products held on May 9-10, 1976
in OTC Vol. 170010, Docket No. FDA-1981-N-0012 (formerly 1981N-
0022), Division of Dockets Management.
14. Gould, W. L., ``On the Use of a Medicament to Reduce the
Appetite in the Treatment of Obesity and Other Conditions,'' New
York State Journal of Medicine, 47:981-983, 1947.
15. Gould, W. L., ``Obesity and Hypertension: The Importance of a
Safe Compound to Control Appetite,'' North Carolina Medical Journal,
11:327-334, 1950.
16. Plotz, M., ``Obesity,'' Medical Times, 86:860-863, 1958.
17. McClure, C. W. and C. A. Brusch, ``Treatment of Oral Syndrome
Obesity with Non traditional Appetite Control Plan,'' Journal of the
American Women's Medical Association, 28:239-248, 1973.
List of Subjects in 21 CFR Part 310
Administrative practice and procedure, Drugs, Labeling, Medical
devices, Reporting and recordkeeping requirements.
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 310 be amended as follows:
PART 310--NEW DRUGS
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.
2. Section 310.545 is amended by adding paragraphs (a)(20)(i),
(a)(20)(ii), and (a)(20)(iii); by revising paragraph (d) introductory
text; and by adding paragraph (d)(40) to read as follows:
Sec. 310.545 Drug products containing certain active ingredients
offered over-the-counter (OTC) for certain uses.
(a) * * *
(20) * * *
(i) [Reserved]
(ii) [Reserved]
(iii) Approved as of [DATE 30 DAYS AFTER DATE OF PUBLICATION OF THE
FINAL RULE IN THE FEDERAL REGISTER].
Benzocaine
* * * * *
(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)(40) of this section.
* * * * *
(40) [DATE 30 DAYS AFTER DATE OF PUBLICATION OF THE FINAL RULE IN
THE FEDERAL REGISTER], for products subject to paragraph (a)(20)(iii)
of this section.
Dated: March 2, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-5145 Filed 3-8-11; 8:45 am]
BILLING CODE 4160-01-P