[Federal Register Volume 70, Number 3 (Wednesday, January 5, 2005)]
[Proposed Rules]
[Pages 741-746]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-154]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 357
[Docket No. 1982N-0166]
RIN 0910-AF51
Orally Administered Drug Products for Relief of Symptoms
Associated With Overindulgence in Food and Drink for Over-the-Counter
Human Use; Proposed Amendment of the Tentative Final Monograph
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend
the tentative final monograph (TFM) for over-the-counter (OTC) orally
administered drug products for relief of symptoms associated with
overindulgence in food and drink to include an additional use for
products that contain bismuth subsalicylate as an active ingredient
labeled for the relief of symptoms of upset stomach due to
overindulgence resulting from food and drink. This proposal is part of
FDA's ongoing review of OTC drug products.
DATES: Submit written or electronic comments by April 5, 2005. Please
see section X of this document for the proposed effective date of any
final rule that may publish based on this proposal.
ADDRESSES: You may submit comments, identified by Docket No. 1982N-0166
or RIN 0910-AF51, by any of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
Agency Web site: http://www.fda.gov/dockets/ecomments.
Follow the instructions for submitting comments on the agency Web site.
E-mail: [email protected]. Include Docket No. 1982N-
0166 or RIN 0910-AF51 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. or Regulatory Information Number (RIN) for this rulemaking.
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 ``Request for
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/ecommentsand/or the
Division of Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville,
MD 20852.
FOR FURTHER INFORMATION CONTACT: Gerald M. Rachanow, Center for Drug
Evaluation and Research (HFD-560), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-2307.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of October 1, 1982 (47 FR 43540), FDA
published an advance notice of proposed rulemaking to establish a
monograph for OTC orally administered drug products for relief of
symptoms associated with overindulgence in alcohol and food, together
with the recommendations of the Advisory Review Panel on OTC
Miscellaneous Internal Drug Products (the Panel), which was the
advisory review panel responsible for evaluating data on the active
ingredients in these drug products (Sec. 330.10(a)(6) (21 CFR
330.10(a)(6))).
In the Federal Register of December 24, 1991 (56 FR 66742), FDA
published the proposed rule (in the form of a TFM) for OTC orally
administered drug products for relief of symptoms associated with
overindulgence in food and drink. In the Federal Register of May 5,
1993 (58 FR 26886), FDA proposed to amend the overindulgence TFM to
include a Reye's syndrome warning for OTC drug products containing
bismuth subsalicylate. In the
[[Page 742]]
Federal Register of April 17, 2003 (68 FR 18861), FDA published a final
rule to revise the Reye's syndrome warning (Sec. 201.314(h) (21 CFR
201.314(h))) to include OTC drug products containing nonaspirin
salicylates (e.g., bismuth subsalicylate) as active ingredients. FDA
stated that there was no need to address this warning in a separate
rule for overindulgence drug products containing bismuth subsalicylate
(68 FR 18861 at 18862). Thus, the April 17, 2003, final rule completed
the May 5, 1993, proposed rule. Products containing bismuth
subsalicylate as an active ingredient must contain the required Reye's
syndrome warning statement as of April 19, 2004, except that products
with annual sales less than $25,000 have until April 18, 2005, to be in
compliance.
In the Federal Register of March 17, 1999 (64 FR 13254), FDA
established a standardized format and content for the labeling of all
OTC drug products (see Sec. 201.66). The labeling in the TFM and the
labeling in this amendment are not in that format. However, the
labeling in the final monograph (FM) will incorporate the standardized
labeling format and content. In response to the TFM, FDA received a
number of comments and is addressing part of one comment in this
document. The remaining comments will be addressed in the final rule.
All ``OTC Volumes'' cited throughout this document refer to information
on public display in the Division of Dockets Management (see
ADDRESSES).
II. The Comment's Recommendation, Arguments, and Data
One comment recommended that FDA include combination upset stomach/
antiflatulent (antigas) drug products containing bismuth subsalicylate
and simethicone in the overindulgence monograph for the relief of upset
stomach and gas due to overindulgence in food and drink. The comment
provided the following arguments and data to support its
recommendation.
FDA's ``General Guidelines for OTC Drug Combination
Products, September 1978'' (Ref. 1) provide that Category I active
ingredients from different therapeutic categories may be combined to
treat different symptoms concurrently if each ingredient is present
within its established safe and effective dosage range, and the
combination meets the OTC drug combination policy in all other
respects. FDA's OTC drug combination regulations (Sec.
330.10(a)(4)(iv)) provide that an OTC drug may combine two or more safe
and effective active ingredients and may be generally recognized as
safe and effective when each active ingredient makes a contribution to
the claimed effect(s); when combining of the active ingredients does
not decrease the safety or effectiveness of any of the individual
active ingredients; and when the combination, when used under adequate
directions for use and warnings against unsafe use, provides rational
concurrent therapy for a significant proportion of the target
population. A combination drug product containing bismuth subsalicylate
and simethicone would combine two Category I active ingredients as
specified in these Guidelines and meet the requirements of this
regulation.
FDA proposed bismuth subsalicylate as safe and effective
for the relief of symptoms of upset stomach associated with
overindulgence in food and drink in the TFM, and simethicone is
included in the antiflatulent monograph (21 CFR part 332). Bismuth
subsalicylate acts in the stomach to relieve upset stomach/indigestion
symptoms such as nausea, heartburn, and fullness, while simethicone
acts in the stomach to break up gas bubbles resulting from
overindulgence in food and drink. Together, these active ingredients
will provide relief from upset stomach symptoms occurring in the
presence of gas.
Combining the active ingredients does not decrease the
safety and effectiveness of either ingredient. The comment cited data
to support that (1) Bismuth subsalicylate does not decrease the foam-
reducing capacity of simethicone (Ref. 2), (2) serum salicylate
bioavailability of a combination of bismuth subsalicylate-simethicone
was equivalent to bismuth subsalicylate alone in dogs (Ref. 3), and (3)
the combination and bismuth subsalicylate alone in rats provided
equivalent stomach protection against alcohol (Ref. 4).
The combination provides rational concurrent therapy for a
significant proportion of the target population. The comment noted a
consumer study of 285 subjects suffering from upset stomach due to
overindulgence in which 56 percent of the subjects reported gas as one
of their symptoms (Ref. 5). The comment mentioned another consumer
study of 159 adults who reported having gas concurrently with symptoms
for which bismuth subsalicylate has been shown to be effective (Ref.
6). The percent of adults reporting gas with each symptom included:
Fullness/bloating (57), upset stomach (55), indigestion (44), and
heartburn (24).
Antacid-simethicone combination products were included in
the antacid monograph (21 CFR part 331) and the antiflatulent monograph
without any supporting clinical data. FDA's determination to allow this
combination was based on a reasonable expectation that simethicone will
be effective if used in combination with an antacid drug product (38 FR
31260 at 31266, November 12, 1973). Further, FDA has proposed that any
antacid covered by the antacid monograph may be labeled ``for the
relief of * * * upset stomach associated with * * * overindulgence in
food and drink'' (56 FR 66754 at 66756, December 24, 1991). FDA did not
review any clinical data to support the indication of upset stomach and
gas due to overindulgence in food and drink.
III. FDA's Evaluation of the Comment's Recommendation
FDA has evaluated the comment's recommendation and reconsidered the
Panel's review of bismuth subsalicylate for the relief of symptoms of
upset stomach associated with overindulgence in food and drink. The
Panel stated that upset stomach that occurs as a result of
overindulgence in food and drink consists of a group of symptoms that
includes heartburn, fullness, and nausea (47 FR 43540 at 43543 and
43545). One of the indications statements that the Panel recommended
for products containing bismuth subsalicylate included these symptoms:
``For the relief of upset stomach associated with'' (select one or more
of the following: ``nausea,'' ``heartburn,'' and ``fullness'') ``due to
overindulgence in the combination of food and drink.'' (See 47 FR 43540
at 43550 and 43558.) FDA proposed this indication statement without the
words ``the combination of'' in Sec. 357.950(b)(2) of the TFM (see 56
FR 66742 at 66751).
The Panel discussed the consumer study of 285 subjects (Ref. 5) (47
FR 43540 at 43545), cited by the comment, and noted that 96 percent of
the subjects had at least one of the symptoms of ``gas (fullness),
heartburn (or acid indigestion), or nausea'' and that 56 percent [the
highest percentage] reported gas as one of their symptoms. The Panel
cited studies by Newsom (Ref. 7) and by Berkowitz (Ref. 8) (47 FR 43540
at 43548 to 43549) to support the effectiveness of bismuth
subsalicylate for treating upset stomach due to overindulgence. The
Newsom study was subsequently published in the Archives of Internal
Medicine (Ref. 9).
Newsom conducted a randomized, placebo-controlled, double-blind,
multiple-crossover study (Refs. 7 and 9) to evaluate the effectiveness
of bismuth
[[Page 743]]
subsalicylate to relieve symptoms in subjects with a history of
episodic, acute (having a short and relatively severe course)
indigestion. The study involved 48 adult subjects 18 to 49 years old
(20 men, 28 women). Two additional subjects began the study but were
later excluded by the investigator because of abnormal laboratory
values. The study medication consisted of either 16.7 milligrams per
milliliter (mg/mL) of bismuth subsalicylate suspended in the vehicle or
a placebo of vehicle only. The two preparations were similar in
appearance, flavor, and viscosity. Each subject received three bottles
of each formulation with a computer-generated random sequence of use
for treating six episodes over a 7-month period. The subjects were
instructed to take the study medication only when they experienced two
or more of the symptoms and to take 30 mL every 30 minutes as needed
for a total of eight doses (up to 240 minutes). Subjects recorded
specific symptoms and the time they first occurred, rating symptom
severity on a 10-point scale 15 and 30 minutes after each dose.
Subjects reported the time when relief occurred. After six episodes,
each subject evaluated each preparation three times.
Newsom defined indigestion or acute gastrointestinal discomfort as
a symptom complex consisting of two or more of the following symptoms
occurring during or after ingestion of food: Nausea, heartburn, upper-
abdominal pain, flatulence (gas) and eructation (belching), sense of
fullness, or a feeling of abdominal distention. Stedman's Medical
Dictionary (Ref. 10) defines indigestion as a nonspecific term for a
variety of symptoms resulting from a failure of proper digestion and
absorption of food in the alimentary tract [relating to the organs of
digestion]. FDA notes that the investigator's definition of indigestion
or acute gastrointestinal discomfort is consistent with the Stedman's
definition in that the dictionary's term is nonspecific and the
investigator's symptoms relate to the digestive system.
The 48 test subjects had no significant differences in reported
symptoms or identified causes in the six individual episodes of
symptoms. Eating specific foods was the most commonly identified cause
of symptoms, followed by overeating. The overall relief of symptoms
showed more episodes treated with bismuth subsalicylate were relieved
(132/144) than were episodes treated with placebo (121/144). However,
the difference between the two groups was not statistically significant
(0.05 stomach queasiness/nausea
heartburn
sense of fullness/bloated feeling
belching
bitter or acid taste in mouth
passing gas/wind
stomach pain/cramps
other symptoms
The subjects were instructed to take 30 mL of the test medication when
symptoms first occurred and to repeat the dose every 30 to 60 minutes,
if needed, up to eight doses. The test medication (bismuth
subsalicylate) and the placebo were prepared as white, opaque
suspensions identical in flavor and viscosity. However, Berkowitz did
not mention the concentration of the bismuth subsalicylate preparation.
Subjects recorded the time the dose was taken and the degree of relief
obtained (none, poor, good, excellent).
Ninety-one of the 132 subjects developed symptoms that required
medication, with 43 taking bismuth subsalicylate and 48 taking placebo.
Comparison of the two groups showed no significant demographic or
baseline differences. The number of subjects and the percent of 91
total subjects reporting the symptoms were as follows:
stomach queasiness/nausea - 50 (55%)
heartburn - 48 (53%)
sense of fullness/bloated feeling - 66 (73%)
belching - 50 (55%)
bitter or acid taste in mouth - 18 (20%)
passing gas/wind - 30 (33%)
stomach pain/cramps - 17 (19%)
The number of symptoms reported is greater than the number of subjects
because subjects reported more than one symptom. Berkowitz performed a
statistical analysis of the four relief categories for each symptom and
for overall relief. Berkowitz found that bismuth subsalicylate was
significantly more effective than placebo for each category except
bitter/acid taste. When the analysis was done using (1) Two relief
categories (none and poor counted as failure, and good and excellent
counted as success) and (2) time to good or excellent relief for each
symptom, Berkowitz found that bismuth subsalicylate was significantly
more effective and provided significantly faster relief than placebo
for relief of nausea, fullness, heartburn, belching, and overall
relief. There was no statistical difference in relief of stomach pain/
cramps, passing gas, and bitter/acid taste. FDA finds that, although
all data are not clearly shown in this study, the results support that
bismuth subsalicylate is effective in relieving nausea, heartburn,
fullness, and belching. FDA notes that the medical definitions of
flatulence, eructation, and bloating are defined using the word gas.
While ``fullness'' is not defined in Stedman's Medical Dictionary (Ref.
10) or in Dorland's Illustrated Medical Dictionary (Ref. 11), Berkowitz
combined the term ``fullness'' with the term ``bloating,'' which refers
to abdominal distention from swallowing air or from intestinal gas, and
showed that bismuth subsalicylate relieved fullness and bloating.
FDA notes that, in evaluating the consumer study of 285 subjects
(Ref. 5) (47 FR 43540 at 43545), the Panel noted that 96 percent of the
subjects had at least one of the symptoms of gas (fullness), heartburn
(or acid indigestion), or nausea, and that 56
[[Page 744]]
percent [the highest percentage] reported gas as one of their symptoms.
Nonetheless, the Panel used the term ``fullness'' (and not ``gas'') in
its proposed indication for overindulgence drug products containing
bismuth subsalicylate (47 FR 43540 at 43558). FDA believes that the
Panel also found that bismuth subsalicylate relieves gas due to
overindulgence in food and drink, but chose to use the word
``fullness'' instead in its recommended indications statement. FDA also
points out that its current indications statement for OTC antiflatulent
drug products containing simethicone in Sec. 332.30(b)(2) states:
``(Select one of the following: `Alleviates' or `Relieves') (select one
or more of the following: `bloating,' `pressure,' `fullness,' or
`stuffed feeling') `commonly referred to as gas'.'' Thus, FDA already
acknowledges that the term ``fullness'' encompasses the term ``gas.''
As the comment noted, the combination of bismuth subsalicylate and
simethicone is subject to FDA's combination drug policy (see section II
of this document). However, FDA notes that a bismuth subsalicylate-
simethicone combination is different than the antacid-simethicone
combination that the comment discussed. Simethicone is a monograph
ingredient (see Sec. 332.10) for antiflatulent use (to relieve
fullness and bloating commonly referred to as gas). Bismuth
subsalicylate is not included in the antacid monograph but based on the
information and analysis in this document has an antigas
(antiflatulent) effect when relieving symptoms of overindulgence in
food and drink. This analysis and finding are new information that the
comment did not have when it proposed a bismuth subsalicylate-
simethicone combination product.
FDA's regulation in Sec. 330.10(a)(4) sets forth the standard for
determining whether a combination drug product may be generally
recognized as safe and effective and not misbranded. Section
330.10(a)(4)(iv) states that ``an OTC drug may combine two or more safe
and effective active ingredients and may be generally recognized as
safe and effective when each active ingredient makes a contribution to
the claimed effect(s) * * *.'' FDA's ``General Guidelines for OTC Drug
Combination Products, September 1978'' [``Combination Product
Guidelines''] (Ref. 1) state that Category I active ingredients from
the same therapeutic category [``antiflatulent'' in this case] that
have the same mechanism of action may be combined in selected
circumstances to treat the same symptoms if:
The combination meets the OTC combination policy in all
respects;
the combination offers some advantage over the active
ingredients used alone; and
the combination is, on a benefit-risk basis, equal to or
better than each of the active ingredients used alone at its
therapeutic dose.
The ``Combination Product Guidelines'' (Ref. 1) list similar factors in
assessing combination drug products with active ingredients from the
same therapeutic category that have different mechanisms of action.
FDA does not have any data on the antigas mechanism of action of
bismuth subsalicylate to determine if it is the same or different from
that of simethicone. FDA also has not received any data to date
comparing the antigas effectiveness of a combination of the two
ingredients versus either individual ingredient. Further, FDA is not
aware of any combination product containing bismuth subsalicylate and
simethicone having been marketed. Therefore, FDA needs data from
clinical studies showing that the combination of bismuth subsalicylate
and simethicone is equal to or better than [offers some advantage over]
each of the individual active ingredients used alone at its therapeutic
dose for this antigas use. FDA recommends that anyone interested in
conducting such studies submit a protocol and meet with the agency
before starting the studies. FDA will evaluate the other data (Refs. 2,
3, and 4) that the comment provided to support this combination product
when the clinical effectiveness studies are submitted to FDA.
IV. FDA's Proposed Amendment of the Tentative Final Monograph
Based on the Newsom (Refs. 7 and 9) and Berkowitz (Ref. 8) studies,
FDA has tentatively determined that bismuth subsalicylate is safe and
effective for OTC use for the relief of upset stomach associated with
belching and gas due to overindulgence in food and drink. FDA proposes
to amend the definition of ``upset stomach due to overindulgence in
food and drink'' proposed in Sec. 357.903 to add the symptoms
``belching'' and ``gas'' and to amend the indications statement for
bismuth subsalicylate proposed in Sec. 357.950(b)(2) to add
``belching'' and ``gas'' as two additional symptoms that manufacturers
may select to include in the labeling of these products.
V. Analysis of Impacts
FDA has examined the impacts of this proposed 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). The Regulatory
Flexibility Act requires agencies to analyze regulatory options that
would minimize any significant impact of a rule on small entities.
Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires
that agencies prepare a written statement of anticipated costs and
benefits before proposing any rule that may result in an expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100 million (adjusted annually for inflation) in
any one year.
FDA believes that this proposed rule is consistent with the
principles set out in Executive Order 12866 and in these two statutes.
The proposed rule is not a significant regulatory action as defined by
the Executive order and so is not subject to review under the Executive
order. The Unfunded Mandates Reform Act of 1995 does not require FDA to
prepare a statement of costs and benefits for this proposed rule,
because the proposed rule is not expected to result in any 1-year
expenditure that would exceed $100 million adjusted for inflation. The
current inflation adjusted statutory threshold is about $110 million.
The purpose of this proposed rule is to expand an indications
statement for OTC overindulgence drug products that contain bismuth
subsalicylate as their active ingredient. The proposal provides
manufacturers the option of including two additional symptoms in their
product's indications statement. As this additional labeling is
optional, manufacturers may elect to implement it whenever they revise
product labeling or may elect not to include the additional information
at all. FDA is unable to state exactly how many bismuth subsalicylate
products have an overindulgence claim because these products may be
marketed with other claims (e.g., for diarrhea) and not have an
overindulgence claim. FDA's Drug Listing System (DLS) identifies 334
OTC drug products that contain bismuth subsalicylate and are marketed
for use
[[Page 745]]
as an antidiarrheal. Some of these products may also have a claim for
overindulgence or may want to include a claim for overindulgence.
Because these products could be marketed with an overindulgence claim,
FDA is counting all such products as potentially affected by this
proposed rule. However, because any relabeling resulting from this
proposed rule is completely voluntary and can be done when
manufacturers are ordering new product labeling, FDA considers any
costs resulting from this proposed rule to be negligible. FDA
recognizes that frequent labeling redesigns are a recognized cost of
doing business in the OTC drug industry. Manufacturers that make
voluntary market-driven changes to their labeling can usually do so at
a nominal cost. FDA recognizes benefits to both manufacturers and
consumers from this proposed labeling change. Manufacturers will have
two additional uses for these products to promote to consumers, and
consumers will be able to use a single product instead of two products
(one for overindulgence and one for gas) to relieve their symptoms
resulting from overindulgence in food and drink. FDA did not consider
other labeling alternatives.
This analysis shows that FDA has considered the burden to small
entities. Therefore, FDA certifies that this proposed rule will not
have a significant economic impact on a substantial number of small
entities. No further analysis is required under the Regulatory
Flexibility Act (5 U.S.C. 605(b)).
VI. Paperwork Reduction Act of 1995
FDA tentatively concludes that the labeling proposed in this
document is not subject to review by the Office of Management and
Budget because they do not constitute a ``collection of information''
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq.).
Rather, the proposed labeling is a ``public disclosure of information
originally supplied by the Federal government to the recipient for the
purpose of disclosure to the public'' (5 CFR 1320.3(c)(2)).
VII. 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.
VIII. Federalism
FDA has analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. FDA has determined that
the proposed 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 tentatively concludes that the proposed rule does not contain
policies that have federalism implications as defined in the Executive
order and, consequently, a federalism summary impact statement has not
been prepared.
IX. Request for Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
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.
X. Proposed Effective Date
FDA is proposing that any final rule that may be issued based on
this proposal be included in the future FM for OTC orally administered
drug products for relief of symptoms associated with overindulgence in
food and drink and have the same effective date as that FM.
XI. References
The following references are on display in the Division of Dockets
Management (see ADDRESSES), under Docket No. 1982N-0166 unless
otherwise noted, and may be seen by interested persons between 9 a.m.
and 4 p.m., Monday through Friday.
1. FDA, ``General Guidelines for OTC Drug Combination Products,
September 1978,'' Division of Dockets Management, Docket No. 1978D-
0322.
2. The Procter & Gamble Co., ``In-vitro Foam Reducing Capacity
Test: Pepto-Bismol With Simethicone,'' in C12.
3. Lukacovic, M. F. and K. J. Watters, ``Dog Bioavailability Study
With Pentagastrin--Pepto-Bismol With Simethicone, PBDB 14,''
The Procter & Gamble Co., in C12, 1992.
4. Lukacovic, M. F. and K. J. Watters, ``Rat Gastric Lesion Study-
Pepto-Bismol With Simethicone. EtOH Study--ANTR 53,'' The
Procter & Gamble Co., in C12, 1991.
5. Comment 31-11370, Division of Dockets Management, Docket No.
1978N-0263.
6. ``Study PD 0292-07,'' The Procter & Gamble Co., in C12.
7. Newsom, J. H., ``Evaluation of Bismuth Subsalicylate in
Relieving Symptoms of Indigestion,'' OTC Vol. 170208 (pp. 15-17).
8. Berkowitz, J. M., ``Bismuth Subsalicylate in Excessive Alcohol/
Food Intake,'' OTC Vol. 170208 (pp. 11-15).
9. Hailey, F. J. and J. H. Newsom, ``Evaluation of Bismuth
Subsalicylate in Relieving Symptoms of Indigestion,'' Archives of
Internal Medicine, 144:269-272, 1984.
10. Stedman's Medical Dictionary, 25th ed., Williams & Wilkins,
Baltimore, MD, s.v. ``indigestion,'' 1990.
11. Dorland's Illustrated Medical Dictionary, 28th ed., W. B.
Saunders Co., Philadelphia, PA, 1994.
List of Subjects in 21 CFR Part 357
Labeling, Over-the-counter drugs, Reporting and recordkeeping
requirements.
0
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 357, as proposed in the Federal Register of
December 24, 1991 (56 FR 66742), be amended as follows:
PART 357--MISCELLANEOUS INTERNAL DRUG PRODUCTS FOR OVER-THE-COUNTER
HUMAN USE
0
1. The authority citation for 21 CFR part 357 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
2. Section 357.903 is amended by revising paragraph (a) to read as
follows:
Sec. 357.903 Definitions.
* * * * *
(a) Upset stomach due to overindulgence in food and drink. A
condition that occurs as a result of overindulgence in food and drink
and consists of a group of symptoms that includes heartburn, nausea,
fullness, belching, and gas.
* * * * *
0
3. Section 357.950 is amended by revising paragraph (b)(2) to read as
follows:
[[Page 746]]
Sec. 357.950 Labeling of drug products for the relief of symptoms of
upset stomach due to overindulgence in food and drink.
* * * * *
(b) * * *
(2) ``For the relief of upset stomach associated with'' (select one
or more of the following: ``nausea,'' ``heartburn,'' ``fullness,''
``belching,'' and ``gas'') ``due to overindulgence in food and drink.''
* * * * *
Dated: December 15, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-154 Filed 1-4-05; 8:45 am]
BILLING CODE 4160-01-S