
[Federal Register Volume 76, Number 46 (Wednesday, March 9, 2011)]
[Proposed Rules]
[Pages 12916-12920]
From the Federal Register Online via the Government Printing 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


