[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



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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