[Federal Register: May 12, 2004 (Volume 69, Number 92)]
[Rules and Regulations]
[Page 26301-26302]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr12my04-2]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 335
[Docket No. 1978N-036T]
RIN 0910-AC82
Antidiarrheal Drug Products for Over-the-Counter Human Use;
Amendment of Final 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 final monograph (FM) for over-the-counter (OTC)
antidiarrheal drug products to include relief of travelers' diarrhea as
an indication for products containing bismuth subsalicylate. Travelers'
diarrhea occurs in travelers and is most commonly caused by an
infectious agent. This final rule is part of FDA's ongoing review of
OTC drug products.
DATES: This rule is effective June 11, 2004.
FOR FURTHER INFORMATION CONTACT: Mary S. Robinson, Center for Drug
Evaluation and Research (HFD-560), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-2222.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of March 21, 1975 (40 FR 12902), FDA
published under 21 CFR 330.10(a)(6) an advance notice of proposed
rulemaking to establish a monograph for OTC antidiarrheal drug
products, together with the recommendations of the Advisory Review
Panel on OTC Laxative, Antidiarrheal, Emetic, and Antiemetic Drug
Products, which evaluated these drug classes. FDA published the
proposed rule in the Federal Register of April 30, 1986 (51 FR 16138),
as a tentative final monograph.
FDA discussed a travelers' diarrhea claim for bismuth subsalicylate
in the final rule for OTC antidiarrheal drug products (68 FR 18869,
April 17, 2003). Travelers' diarrhea is an acute diarrheal illness
occurring among travelers, particularly those visiting developing
countries where sanitation is suboptimal. Most cases of travelers'
diarrhea are caused by infectious agents, acquired through the
ingestion of fecally contaminated food and/or water. Bacterial
pathogens account for the great majority of episodes. Overall, one of
the most common etiologic agents in travelers' diarrhea are
enterotoxigenic Escherichia coli, which are responsible for 50 to 75
percent of episodes in certain areas of the world. Other recognized
enteropathogens can be isolated from most of the remainder of cases,
but with great regional differences in prevalence. Viruses (rotavirus,
Norwalk-like virus) and protozoa (amebas, Giardia) are collectively
responsible for fewer than 10 percent of cases of travelers' diarrhea.
FDA discussed the clinical data for this claim in section II,
comment 3 of the final rule for OTC antidiarrheal drug products (68 FR
18869 at 18871). FDA has determined that the data support the use of
bismuth subsalicylate in treating the symptoms of travelers' diarrhea.
Accordingly, FDA is amending the FM to include an indication
[``controls'' or ``relieves'' ``travelers' diarrhea''] for OTC
antidiarrheal drug products containing bismuth subsalicylate identified
in 21 CFR 335.10(a).
II. FDA's Conclusions on the Comment
In response to the proposal, FDA received one comment, which is on
public display in the Division of Dockets Management (HFA-305), 5630
Fishers Lane, rm. 1061, Rockville, MD 20852. The comment agreed
completely with the proposal to amend the FM for OTC antidiarrheal drug
products to include the additional indication for travelers' diarrhea
for products containing bismuth subsalicylate. The comment encouraged
FDA to expeditiously amend the FM so this indication can be used on
appropriate OTC drug products.
FDA agrees with the comment and is providing that this final rule
be effective 30 days after its date of publication.
III. FDA's Final Conclusions
FDA is amending the FM for OTC antidiarrheal drug products to make
the following additions:
Definitions in 21 CFR 335.3(c): ``Travelers' diarrhea. A
subset of diarrhea occurring in travelers that is most commonly caused
by an infectious agent.''
Indications in 21 CFR 335.50(b)(1) for products containing
bismuth subsalicylate: [select one of the following: ``controls'' or
``relieves''] *** ``travelers' diarrhea'']. If both ``diarrhea'' and
``travelers' diarrhea'' are selected, each shall be preceded by a
bullet in accordance with 21 CFR 201.66(b)(4) and (d)(4) of this
chapter and the heading ``Uses'' shall be used.
IV. Analysis of Impacts
FDA has examined the impacts of the final 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). Under the Regulatory
Flexibility Act, if a rule has a significant economic impact on a
substantial number of small entities, an agency must analyze regulatory
options that would minimize any significant impact of the 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 in any one year by State, local, and tribal governments, in
the aggregate, or by the private sector, of $100 million (adjusted
annually for inflation).
FDA concludes that this final rule is consistent with the
principles set out in Executive Order 12866 and in these two statutes.
The final rule is not a significant regulatory action as defined by the
Executive order and so is not subject to review under the Executive
order. As discussed in this section of the document, FDA has determined
that this final rule will not have a significant economic impact on a
substantial number of small entities. The Unfunded Mandates Reform Act
does not require FDA to prepare a statement of costs and benefits for
this final rule, because the final 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 final rule is to provide an additional
(optional) claim for OTC antidiarrheal drug products containing bismuth
subsalicylate. Manufacturers can add this claim to
[[Page 26302]]
their labeling when ordering new product labeling to be in compliance
with the OTC antidiarrheal drug products FM. Adding this claim might
result in additional product sales but, in any case, is completely
optional. Thus, this final rule will not impose a significant economic
burden on affected entities. Therefore, FDA certifies that this final
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)).
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
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.
VII. Federalism
FDA has analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. FDA has determined that the 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, the agency concludes that
the rule does not contain policies that have federalism implications as
defined in the Executive order and, consequently, a federalism summary
impact statement is not required.
List of Subjects in 21 CFR Part 335
Labeling, Over-the-counter drugs.
0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
335 is amended as follows:
PART 335--ANTIDIARRHEAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN
USE
0
1. The authority citation for 21 CFR part 335 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
0
2. Section 335.3 is amended by adding paragraph (c) to read as follows:
Sec. 335.3 Definitions.
* * * * *
(c) Travelers' diarrhea. A subset of diarrhea occurring in
travelers that is most commonly caused by an infectious agent.
0
3. Section 335.50 is amended by revising paragraph (b)(1) to read as
follows:
Sec. 335.50 Labeling of antidiarrheal drug products.
* * * * *
(b) * * *
(1) For products containing bismuth subsalicylate identified in
Sec. 335.10(a). The labeling states [select one of the following:
``controls'' or ``relieves''] [select one or both of the following:
``diarrhea'' or ``travelers' diarrhea'']. If both ``diarrhea'' and
``travelers' diarrhea'' are selected, each shall be preceded by a
bullet in accordance with Sec. 201.66(b)(4) and (d)(4) of this chapter
and the heading ``Uses'' shall be used.
* * * * *
Dated: May 3, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-10750 Filed 5-11-04; 8:45 am]
BILLING CODE 4160-01-S