[Federal Register Volume 69, Number 92 (Wednesday, May 12, 2004)]
[Rules and Regulations]
[Pages 26301-26302]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-10750]


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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