[Federal Register Volume 68, Number 74 (Thursday, April 17, 2003)]
[Proposed Rules]
[Pages 18915-18917]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-9381]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 335

[Docket No. 78N-036T]
RIN 0910-AA01


Antidiarrheal Drug Products for Over-the-Counter Human Use; 
Proposed Amendment of Final Monograph

AGENCY: Food and Drug Administration.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is issuing a proposed 
rule that would amend the final monograph 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 proposal is part of FDA's ongoing review of OTC 
drug products.

DATES: Submit written or electronic comments by July 16, 2003; written 
or electronic comments on the agency's economic impact determination by 
July 16, 2003. Please see section VIII of this document for the 
effective date of any final rule that may publish based on this 
proposal.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments.

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

[[Page 18916]]

Advisory Review Panel on OTC Laxative, Antidiarrheal, Emetic, and 
Antiemetic Drug Products, which evaluated these drug classes. The 
proposed rule was published in the Federal Register of April 30, 1986 
(51 FR 16138), as a tentative final monograph.
    In response to the proposed rule, one manufacturer requested a 
travelers' diarrhea claim for bismuth subsalicylate (Ref. 1). 
Travelers' diarrhea is an acute diarrheal illness occurring among 
travelers, particularly those visiting developing countries where 
sanitation is suboptimal. Virtually all 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 (Ref. 2).
    The clinical data for this claim are discussed in section II, 
comment 3 of the final rule for OTC antidiarrheal drug products, 
published elsewhere in this issue of the Federal Register. The agency 
has tentatively determined that the data support the use of bismuth 
subsalicylate in treating the symptoms of travelers' diarrhea. 
Accordingly, the agency is proposing to amend the final monograph to 
include ``relieves travelers' diarrhea'' as a monograph indication for 
OTC antidiarrheal drug products containing bismuth subsalicylate 
identified in Sec.  335.10(a).

II. Summary of the Agency's Proposal for Travelers' Diarrhea

    The agency proposes to add the following definition in Sec.  
335.3(c): ``Travelers' diarrhea. A subset of diarrhea occurring in 
travelers that is most commonly caused by an infectious agent.'' The 
agency is also proposing to add the following labeling indication in 
Sec.  335.50(b)(1) for products containing bismuth subsalicylate: ``[* 
* * ``controls'' or ``relieves''] [* * * ``travelers' diarrhea''] * * 
*.'' Products may not be labeled with this claim until the monograph 
amendment process is completed and the agency publishes a final rule in 
a future issue of the Federal Register.

III. Analysis of Impacts

    FDA has examined the impacts of the 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). 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).
    The agency tentatively concludes 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 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 provide an additional 
(optional) claim for OTC antidiarrheal drug products containing bismuth 
subsalicylate. Manufacturers can add this claim to their labeling when 
ordering new product labeling to be in compliance with the OTC 
antidiarrheal drug products final monograph. Adding this claim might 
result in additional product sales but, in any case, is completely 
optional. Thus, this proposed rule will not impose a significant 
economic burden on affected entities. Therefore, the agency 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)).
    The agency invites public comment regarding any substantial or 
significant economic impact that this proposed rule would have on OTC 
antidiarrheal drug products. Types of impact may include, but are not 
limited to, costs associated with relabeling or repackaging. Comments 
regarding the impact of this proposed rule should be accompanied by 
appropriate documentation. A period of 90 days from the date of 
publication of this proposed rule in the Federal Register will be 
provided for comments on this subject to be developed and submitted. 
The agency will evaluate any comments and supporting data that are 
received and will reassess the economic impact of this proposed rule in 
the preamble to the final rule.

IV. Paperwork Reduction Act of 1995

    FDA tentatively concludes that the labeling requirements proposed 
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 proposed 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(a)).

V. Environmental Impact

    The agency 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.

VI. 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, 
the agency 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.

[[Page 18917]]

VII. Request For Comments

    Interested persons may submit written or electronic comments 
regarding this proposal and on the agency's economic impact 
determination to the Dockets Management Branch (see ADDRESSES) by (see 
DATES). Three copies of all written comments are to be submitted, 
except individuals may submit one copy. Comments are to be identified 
with the docket number found in brackets in the heading of this 
document. Received comments may be seen in the Dockets Management 
Branch between 9 a.m. and 4 p.m., Monday through Friday.

VIII. Proposed Effective Date

    The agency is proposing that any final rule that may issue based on 
this proposal become effective 30 days after its date of publication in 
the Federal Register.

IX. References

    The following references are on display in the Dockets Management 
Branch (see ADDRESSES) under Docket No. 78N-036D and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
    1. Comments No. SUP 8, SUP 13, SUP 14, LET 21, LET 23, PR 3, and 
MT 2.
    2. Wilson, J. D. et al., editors, Harrison's Principles of 
Internal Medicine, 12th ed., McGraw-Hill, Inc., New York, NY, pp. 
523-524, 1991.

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, it is 
proposed that 21 CFR part 335 be 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 
``traveler's diarrhea'' are selected, each shall be preceded by a 
bullet in accordance with Sec.  201.66(b)(4) of this chapter and the 
heading ``Uses'' shall be used.
* * * * *

    Dated: March 31, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-9381 Filed 4-16-03; 8:45 am]
BILLING CODE 4160-01-S