[Federal Register Volume 61, Number 44 (Tuesday, March 5, 1996)]
[Rules and Regulations]
[Pages 8836-8839]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-5118]
[[Page 8835]]
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Part IX
Department of Health and Human Services
_______________________________________________________________________
Food and Drug Administration
_______________________________________________________________________
21 CFR Part 332
Antiflatulent Drug Products for Over-the-Counter Human Use; Final Rule
Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules
and Regulations
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[[Page 8836]]
21 CFR PART 332
[DOCKET NO. 87N-0053]
RIN 0910-AA01
Antiflatulent Drug Products for Over-the-Counter Human use;
Amendment of Monograph
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is issuing a final rule
amending the monograph for over-the-counter (OTC) antiflatulent drug
products by adding a statement of identity section to conform to the
format of other OTC drug final monographs and by revising the
indications to include additional descriptive terms, and by adding a
definition for the term ``antigas.'' FDA is issuing this final rule
after considering public comments on the agency's proposed regulation
and all new data and information on OTC antiflatulent drug products
that have come to the agency's attention. This final rule is part of
the ongoing review of OTC drug products conducted by FDA.
DATES: Effective March 5, 1997; written comments by June 3, 1996.
FOR FURTHER INFORMATION CONTACT: William E. Gilbertson, Center for Drug
Evaluation and Research (HFD-105), Food and Drug Administration, 5600
Fishers Lane,-Rockville, MD 20857, 301-827-2304.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of June 4, 1974 (39 FR 19862), FDA issued
a final monograph for OTC antiflatulent drug products (21 CFR part 332)
that established conditions under which these drug products are
generally recognized as safe and effective and not misbranded.
In the Federal Register of January 29, 1988 (53 FR 2716), the
agency published a proposed amendment of the monograph for OTC
antiflatulent drug products to add a statement of identity section to
conform to the format of other OTC drug final monographs and to revise
the indications for use to include additional descriptive terms
describing the symptoms that are commonly referred to as ``gas.'' The
proposed statement of identity was ``antiflatulent,'' antigas,'' or
``antiflatulent (antigas).'' FDA issued that proposal after considering
the report and recommendations of the Advisory Review Panel on OTC
Miscellaneous Internal Drug Products (the Miscellaneous Internal Panel)
and public comments on the advance notice of proposed rulemaking for
OTC digestive aid drug products (47 FR 454, January 5, 1982), that was
based on those recommendations. Interested persons were invited to
submit comments, objections, or requests for oral hearing by March 29,
1988.
In the Federal Register of April 19, 1988 (53 FR 12778 and 12779),
the agency extended the comment period from March 29, 1988, until May
27, 1988, to allow adequate time for one manufacturer to fully evaluate
information it had received from the agency and to prepare comments to
the notices of proposed rulemaking for OTC antiflatulent drug products
and OTC digestive aid drug products.
In response to the proposed monograph amendment, three drug
manufacturers and three physicians submitted comments. One comment
requested an oral hearing before the Commissioner of Food and Drugs.
That request concerned the inclusion of activated charcoal in the OTC
antiflatulent monograph if the ingredient was found to be Category I in
the OTC digestive aid monograph. The agency addressed the hearing
request in comment 1 of the final rule for OTC digestive aid drug
products (58 FR 54450 at 54451, October 21, 1993), and concluded that
activated charcoal will not be included in either monograph, and a
hearing is not necessary.''Copies of the comments and the hearing
request received are on public display in the Dockets Management Branch
(H.A.-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23
Rockville, MD 20857, and may be seen between 9 a.m. and 4 p.m., Monday
through Friday. Any additional information that has come to the
agency's attention since publication of the proposed rule is also on
public display in the Dockets Management Branch.
In proceeding with this final rule, the agency has considered all
comments, objections, and the request for oral hearing. A summary of
the comments and the new data with FDA's responses to them follows.
II. Summary of the Comments Received
1. One comment agreed with the agency's use of the term
``antigas''as interchangeable with ``antiflatulent.'' The comment
expressed concern, however, that the agency was prohibiting other
terminology, e.g., ``antigas formulation relieves gas trapped in the
intestine'' or ``for gas pain.'' The comment stated that the basis for
the agency's labeling restriction appeared to be recommendations of the
Miscellaneous Internal Panel (47 FR 454), which were at variance with
the findings of the Advisory Review Panel on OTC Antacid Drug Products
(38 FR 8714, April 5, 1973) (the Antacid Panel) that recognized the
cause of ``bloating,'' ``pressure,'' and ``fullness'' as being the
result of gas. The comment cited the Antacid Panel's recommended
indication ``alleviate or relieve the symptoms of gas'' for
simethicone-containing products as support for its position that excess
gas causes discomfort. The comment also cited the double-blind,
placebo-controlled clinical study by McDonald, O'Leary, and Stratton
(Ref. 1) as demonstrating that dosing with simethicone results in a
reduction of gastrointestinal foam. Finally, the comment stated that
terms such as ``relieves gas trapped in the intestine,'' ``for gas
pain,'' and ``relieves the symptoms of gas should not be prohibited
under the antiflatulent final monograph because consumers use these
terms. The comment referred, specifically, to the consumer survey
discussed in the proposed amendment (53 FR 2716) and indicated that the
terms `` bloating,'' ``pressure,'' ``stuffed feeling,'' and
``fullness'' are very meaningful to and used by consumers to describe
``gas.'' The comment concluded by stating it is unclear whether the
existing indication in Sec. 332.30(a), ``to alleviate or relieve the
symptoms of gas,'' is still permitted because the proposal appears to
omit this indication.
The agency is no longer including the indication ``to alleviate or
relieve the symptoms of gas'' in the antiflatulent monograph. As
explained in the proposal to amend the antiflatulent monograph (53 FR
2716), the agency modified the wording of this indication to
(``alleviates'' or ``relieves'') ``the symptoms referred to as gas.''
The agency also recognized that consumers use the terms ``bloating,
pressure, fullness,''
`` or ''stuffed feeling ``to refer to gas and provided an additional
indication statement that includes these terms: (``alleviates'' or
``relieves'') (``bloating, pressure, fullness, or stuffed feeling)
commonly referred to as gas.''
The agency disagrees with the comment's statement that the Antacid
Panel recognized the cause of ``bloating,'' ``pressure, ``and
''fullness'' as being the result of gas. The Antacid Panel stated that
claims or indications such as ``full feeling'' or ``gas'' encourage the
user to draw conclusions as to the cause of such symptoms, ``a
conclusion that even the medical profession is incapable of drawing at
this time,'' and placed claims such as ``full feeling'' or ``gas'' in
Category III (38
[[Page 8837]]
FR 8714 at 8722 to 8723). Further, while these symptoms describe
discomfort, as noted by the Antacid Panel, the Panel did not include
``pain'' as one of the symptoms of gas (38 FR 8722 to 8723).
In the proposal to amend the antiflatulent monograph, the agency
also stated that phrases such as ``antigas formulation relieves gas
trapped in the intestine'' and ``for gas pain'' would be considered
inappropriate (53 FR 2716). The agency reviewed the study by McDonald,
O'Leary, and Stratton (Ref. 1), cited by the comment, which discusses
the effectiveness of simethicone in eliminating foam and bubbles that
may obscure the visual field in peroral endoscopy. According to the
study results, simethicone is effective as a defoaming agent, but the
study does not define the term ``bubbles'' or explain the source of the
foam or bubbles that obscure the visual field. Without knowing whether
the bubbles are derived from gas or air, the study cannot support the
phrases ``relieves gas trapped in the intestine'' and ``for gas pain.''
In the advance notice of proposed rulemaking for OTC digestive aid
drug products (47 FR 454), the Miscellaneous Internal Panel discussed
at length the question of whether excessive gas is the causative agent
of distress in the upper gastrointestinal tract and concluded that data
were insufficient to make this assumption. In the tentative final
monograph for OTC digestive aid drug products (53 FR 2706, January 29,
1988), the agency acknowledged that the word ``gas'' is commonly used
by consumers. Therefore, the agency had no objection to use of the word
``gas'' in the labeling of OTC digestive aid drug products, provided
there was no implication that the presence of gas, in the literal sense
of excess gas bubbles in the gastrointestinal tract, is the cause of
the symptoms. The agency discussed the consumer survey mentioned by the
comment and agreed that a number of terms were commonly used by
consumers in describing what is commonly, if not accurately, referred
to as ``gas'' (53 FR 2706 at 2710). However, the terms did not include
``gas pain.''
Based on all of the data evaluated to date, the agency finds the
claims ``antigas formulation relieves gas trapped in the intestine''
and ``for gas pain'' inappropriate for OTC antiflatulent drug products.
The agency concludes that the general term ``antigas'' is appropriate
when used for the indications provided in the monograph, e.g.,
``relieves the symptoms referred to as gas.'' However, the agency
acknowledges that the term could be interpreted by some as the
mechanism of action for these products. While this is not supported
scientifically, the agency concludes that this term is understood by
consumers and is an appropriate statement of identity for these
products.
The agency is adding the following definition for the term
``antigas'' in the monograph: ``Antigas is a term that may be used
interchangeably with the term antiflatulent. Neither term should be
considered as describing the mechanism of action of the active
ingredient contained in the product.'' This definition appears in new
Sec. 332.3 of the final monograph.
Reference
(1) McDonald, G. B., R. O'Leary, and C. Stratton, ``Pre-
Endoscopic Use of Oral-Simethicone,'' Gastrointestinal Endoscopy,
24:283, 1978.
2. Three comments, submitting to both the OTC antiflatulent and
digestive aid drug products rulemakings, contended that activated
charcoal was solely an antiflatulent drug and did not belong in the
digestive aid drug products rulemaking. Another comment expressed
concern that activated charcoal was not included as a monograph
ingredient in the 1988 proposal to amend the final monograph for OTC
antiflatulent drug products. The comments cited studies (Refs. 1
through 5) in the literature to support monograph status for activated
charcoal. One comment mentioned that physicians who use charcoal to
treat lower intestinal gas symptoms indicate that charcoal is effective
under certain circumstances. The comment referred to studies by Jain et
al. (not cited), as well as its own studies (not submitted), as
evidence that activated charcoal decreased intestinal gas and relieved
associated symptoms. The comment argued that the need for additional
studies and ongoing research should not deter the availability or use
of activated charcoal for excessive gas and related symptoms for which
it is reasonably expected to be effective. The comment felt charcoal
was not approved because it had a stigma as ``an old remedy,'' which is
difficult to overcome.
Two advisory review panels (Antacid (38 FR 8714) and Miscellaneous
Internal (47 FR 454)) evaluated charcoal for antiflatulent and
digestive aid use. Both panels concluded that more data were needed to
establish effectiveness for these uses.
Subsequently, after the comments were submitted, the agency
received additional data, including studies done by one comment and by
Jain et al. (referenced by the comment). The agency discussed these
studies and the references provided by the comments in the final rule
for OTC digestive aid drug products (58 FR 54450 at 54451). The agency
found the data insufficient to support the effectiveness of activated
charcoal as a digestive aid or as an antiflatulent (58 FR 54453). No
new data have been provided to the agency.
The agency has never attached a ``stigma'' to a drug because it
has been in the marketplace for many years. The agency has proposed a
number of very old ingredients (e.g., aspirin, bran, cascara, and
psyllium) as monograph ingredients. The data that have been provided
have not been adequate to include activated charcoal in a monograph for
use as an antiflatulent. Manufacturers have the option to petition the
agency to amend the antiflatulent monograph in the future should
additional data become available to support the effectiveness of
activated charcoal as an antiflatulent.
References--
(1) Jain, N. K. et al., ``Efficacy of Activated Charcoal in
Reducing Intestinal Gas: A Double-Blind Clinical Trial,'' American
Journal of Gastroenterology, 81:532-535, 1986.--
(2) Jain, N. K., V. P. Patel, and C. Pitchumoni, ``Activated
Charcoal, Simethicone, and Intestinal Gas: A Double-Blind Study,''
Annals of Internal Medicine, 105:61-62, 1986.--
(3) Potter, T., C. Ellis, and M. Levitt, ``Activated Charcoal:
In Vivo and In Vitro Studies of Effect on Gas Formation,''
Gastroenterology, 88:620624, 1985.
(4) Hall, R. G., H. Thompson, and A. Strother, ``Effects of
Orally Administered Activated Charcoal on Intestinal Gas,'' The
American College of Gastroenterology, 75:192-196, 1981.
(5) Vargo, D., L. Ozick, and M. H. Floch, ``The Effect of
Activated Charcoal on Dietary Carbohydrate Fermentation'' American
Journal of Gastroenterology, (abst.), 82:950, 1987.
3. Three manufacturers submitted protocols to study the
effectiveness of activated charcoal in decreasing gastrointestinal
distress. One manufacturer did not pursue studies after 1989.
The agency met with representatives of the other two manufacturers
(Ref. 1) to discuss their study protocols. Both manufacturers submitted
revised protocols in response to the agency's comments. The agency
provided written comments on only one of the protocols (Ref. 2) because
one manufacturer indicated that it intended to begin its study and that
no further review by the agency was necessary.
Subsequently, one manufacturer informed FDA that it had decided
not to pursue studies (Ref. 3). The other manufacturer (Ref. 4) has not
submitted
[[Page 8838]]
any study results to date. In the absence of new data, the agency
concludes there is no basis to include activated charcoal in the OTC
antiflatulent drug products monograph at this time. -Manufacturers have
the option to petition the agency to amend the antiflatulent monograph
in the future should additional data become available to support the
effectiveness of activated charcoal as an antiflatulent.
References
(1) Memorandum of Meeting between FDA representatives and
representatives from Kramer Laboratories and Requa, Inc., coded MM4,
Docket No. 81N-0106, Dockets Management Branch.
(2) Letter from W. E. Gilbertson, FDA, to J. Geils, Requa,
Inc., dated July 22, 1994, coded LET 20, Docket No. 81N-0106,
Dockets Management Branch.
(3) Memorandum of Telephone Conversation between M. Barach, of
Akin, Gump, Strauss, Hauer & Feld on behalf of Kramer Laboratories,
and B. Ryland, FDA, coded MT3, Docket No. 81N-0106, Dockets
Management Branch.---
(4) Memorandum of Telephone Conversation between B. Marlin,
Requa Consultant, and B. Ryland, FDA, coded MT4, Docket No. 81N-
0106, Dockets Management Branch.-
III. The Agency's Final Conclusions
The agency has carefully evaluated the comments' proposals and
concludes that the terms ``antigas'' and ``antiflatulent'' are
interchangeable. The agency is providing manufacturers the option of
using either term or both as the statement of identity for their
products. Although ``antigas'' is now the preferable term, the agency
is also allowing ``antiflatulent.''
In respect to the one comment's concern that activated charcoal is
not a monograph ingredient, the agency points out that manufacturers of
products containing this ingredient have had over 20 years to provide
sufficient data to support claims for activated charcoal as an
antiflatulent and have failed to do so. Accordingly, simethicone
remains the only antiflatulent monograph ingredient.
Interested persons may, on or before June 3, 1996, submit to the
Dockets Management Branch (address above) written comments on these
warnings. Comments should be identified with the docket number found in
brackets in the heading of this document. Three copies of all comments
are to be submitted, except that individuals may submit one copy.
Received comments may be seen in the office above between 9 a.m. and 4
p.m., Monday through Friday.
IV. Analysis of Impacts
No comments regarding the economic impact of this rulemaking were
received. FDA has examined the final rule under Executive Order 12866
and the Regulatory Flexibility Act (Pub. L. 96-354). 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 agency believes that
this final rule is consistent with the regulatory action as defined by
the Executive Order and, thus, is not subject to review under the
Executive Order. This final rule provides for minor labeling revisions
that can be implemented at very little cost by manufacturers at the
next printing of labels. The agency is providing 12 months for these
revisions to be made and, thus, believes that this rule will have no
significant economic impact. Accordingly, the agency 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 Act of 1995
FDA concludes that the labeling requirements in this document are
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
labeling statements are 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)).
VI. Environmental Impact
The agency has determined under 21 CFR 25.24(c)(6) 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.
List of Subjects in 21 CFR Part 332
Labeling, Over-the-counter drugs.-Therefore, under the Federal
Food, Drug, and Cosmetic Act and under authority delegated to the
Commissioner of Food and Drugs, 21 CFR part 332 is amended as follows:
PART 332--ANTIFLATULENT PRODUCTS FOR OVER-THE-COUNTER HUMAN USE-
1. The authority citation for 21 CFR part 332 is revised to read
as follows:
Authority: Secs. 201, 501, 502, 503, 505, 510, 701 of the
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 351, 352, 353,
355, 360, 371).
2. New Sec. 332.3 is added to Subpart A to read as follows:
Subpart A--General Provisions
Sec. 332.3 Definitions.
As used in this part:
Antigas. A term that may be used interchangeably with the term
antiflatulent. Neither term should be considered as describing the
mechanism of action of the active ingredient contained in the product.
3. Subpart D consisting Sec. Sec. 332.30 and 332.31 is
redesignated as Subpart C; and Sec. 332.30 is amended by revising the
section heading; by redesignating paragraphs (a), (b), and (c) as
paragraphs (b), (c), and (d), respectively; by adding new paragraph
(a); and by revising newly redesignated paragraph (b) to read as
follows:
Subpart--Labeling
Sec. 332.30 Labeling of antiflatulent drug products.
(a) Statement of identity. The labeling of the product contains
the established name of the drug, if any, and identifies the product as
an ``antiflatulent,'' ``antigas,'' or ``antiflatulent (antigas).''
(b) Indications. The labeling of the product states, under the
heading ``Indications,'' one or more of the phrases listed in this
paragraph (b), as appropriate. Other truthful and nonmisleading
statements, describing only the indications for use that have been
established and listed in this paragraph (b), may also be used, as
provided in Sec. 330.1(c)(2) of this chapter, subject to the provisions
of section 502 of the Federal Food, Drug, and Cosmetic Act (the act)
relating to misbranding and the prohibition in section 301(d) of the
act against the introduction or delivery for introduction into
interstate commerce of unapproved new drugs in violation of section
505(a) of the act.
(1) (Select one of the following: ``Alleviates or Relieves'')
``the symptoms referred to as gas.''
(2) (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.''
-* *- * * * -
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Dated: February 23, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordintion.
[FR Doc. 96-5118 Filed 3-4-96; 8:45 am]
BILLING CODE 4160-01-F
