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Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use; Partial Final Rule for Combination Drug Products Containing a Bronchodilator
Note: EPA no longer updates this information, but it may be useful as a reference or resource.
[Federal Register: September 27, 2001 (Volume 66, Number 188)]
[Rules and Regulations]
[Page 49276-49278]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr27se01-6]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration.
21 CFR Part 341
[Docket No. 76N-052G]
RIN 0910-AA01
Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug
Products for Over-the-Counter Human Use; Partial Final Rule for
Combination Drug Products Containing a Bronchodilator
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
establishing that cough-cold combination drug products containing any
oral bronchodilator active ingredient in combination with any
analgesic(s) or analgesic-antipyretic(s), anticholinergic,
antihistamine, oral antitussive, or stimulant active ingredient are not
generally recognized as safe and effective and are misbranded for over-
the-counter (OTC) use. FDA is issuing this final rule after receiving
no public comments on the agency's proposed nonmonograph status of
these specific combination drug products, which was issued in the form
of a tentative final monograph for OTC cough-cold combination drug
products. This final rule is part of the ongoing review of OTC drug
products conducted by FDA.
DATES: This regulation is effective October 29, 2001.
FOR FURTHER INFORMATION CONTACT: Cazemiro R. Martin, 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 September 9, l976 (41 FR 38312), FDA
published, under Sec. 330.10(a)(6) (21 CFR 330.10(a)(6)), an advance
notice of proposed rulemaking to establish a monograph for OTC cold,
cough, allergy, bronchodilator, and antiasthmatic (cough-cold) drug
products, together with the recommendations of the Advisory Review
Panel on OTC Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic
Drug Products (the Panel), which was the advisory review panel
responsible for evaluating data on the active ingredients in this drug
class. The Panel placed the combination of an oral bronchodilator with
either an analgesic-antipyretic, anticholinergic, antihistamine, or
antitussive (when the product is labeled only for cough associated with
asthma) ingredient in Category II (not generally recognized as safe
and/or effective) (41 FR 38312 at 38326).
The agency concurred with the Panel in the tentative final
monograph for cough-cold combination drug products (53 FR 30522 at
30556, August 12, 1988). The agency also classified the combination of
caffeine and ephedrine or pseudoephedrine in Category II (53 FR 30522
at 30557). No comments on these specific combinations were submitted in
response to the tentative final monograph.
The current monograph oral bronchodilator active ingredients are
ephedrine, ephedrine hydrochloride, ephedrine sulfate, and racephedrine
hydrochloride (21 CFR 341.16(a), (b), (c), and (f)). The agency is not
aware of any OTC drug products currently marketed containing an oral
bronchodilator active ingredient in combination with any analgesic(s)
or analgesic-antipyretic(s), anticholinergic, antihistamine, oral
antitussive, or stimulant active ingredient.
II. The Agency's Conclusion
The OTC drug review program establishes conditions under which OTC
drugs are generally recognized as safe and effective and not
misbranded.
[[Page 49277]]
Two principal conditions examined during the review are allowable
ingredients and allowable labeling. The Panel evaluated the submitted
data on active ingredients in combination products from the standpoint
of safety and effectiveness and, based on its evaluation, recommended
specific combinations of ingredients from the same and different
pharmacologic groups. The Panel classified a number of cough-cold
combinations as Category II (41 FR 38312 at 38326) and considered
medical rationale and drug interaction in making these recommendations.
In the tentative final monograph for OTC cough-cold combination
drug products (53 FR 30522 at 30556 to 30557), the agency agreed with
the Panel's recommended Category II status of any oral bronchodilator
active ingredient in combination with any analgesic(s) or analgesic-
antipyretic(s), anticholinergic, antihistamine, oral antitussive, or
stimulant active ingredient. The agency invited interested persons to
submit written comments and new data demonstrating the safety and
effectiveness of those conditions not classified in Category I (53 FR
30522 at 30560). The agency did not receive any comments in response to
its request for such information concerning the proposed Category II
status of any of the above-mentioned OTC cough-cold combination drug
products containing an oral bronchodilator.
Accordingly, in this final rule the agency is finalizing the
nonmonograph status of any oral bronchodilator active ingredient in
combination with any analgesic(s) or analgesic-antipyretic(s),
anticholinergic, antihistamine, oral antitussive, or stimulant active
ingredient. Thus, any drug product labeled, represented, or promoted
for use as an OTC cough-cold combination drug that contains any oral
bronchodilator active ingredients in combination with any of these
specific active ingredients may be considered a new drug within the
meaning of section 201(p) of the Federal Food, Drug, and Cosmetic Act
(the act) (21 U.S.C. 321(p)) and misbranded under section 502 of the
act (21 U.S.C. 352). These specific combination drug products can not
be marketed for OTC cough-cold use unless they are the subject of an
approved application under section 505 of the act (21 U.S.C. 355) and
part 314 of the regulations (21 CFR part 314). Any OTC cough-cold
combination drug product included in new Sec. 310.545(a)(6)(iv)(D) that
is initially introduced or initially delivered for introduction into
interstate commerce after the effective date stated in
Sec. 310.545(d)(33) of this final rule that is not in compliance with
the regulations is subject to regulatory action.
III. Analysis of Impacts
The agency did not receive any comments in response to its request
in the tentative final monograph (53 FR 30522 at 30560) for specific
comment on the economic impact of this rulemaking. FDA has examined the
impacts of this 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 requires
that agencies prepare a written statement and economic analysis before
proposing any rule that may result in an expenditure by State, local,
and tribal governments, in the aggregate, or by the private sector, of
$100 million in any one year (adjusted annually for inflation).
The agency believes that this final rule is consistent with the
regulatory philosophy and principles identified in the Executive order.
In addition, 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.
The purpose of this final rule is to declare any oral
bronchodilator active ingredient in combination with any analgesic(s)
or analgesic-antipyretic(s), anticholinergic, antihistamine, oral
antitussive, or stimulant active ingredient as not generally recognized
as safe and effective. The agency does not believe that any of these
combination drug products are currently marketed OTC. Therefore, this
final rule should have no economic impact on any manufacturer.
Under the Unfunded Mandates Reform Act, FDA is not required to
prepare a statement of costs and benefits for this final rule because
this final rule is not expected to result in an expenditure that would
exceed $100 million adjusted for inflation in any one year.
The agency certifies that the final rule will not have a
significant impact on a substantial number of small entities.
IV. Environmental Impact
The agency has determined under 21 CFR 25.31(a) that this action is
of a type that is categorically excluded from the preparation of an
environmental assessment because these actions, as a class, will not
result in the production or distribution of any substance and therefore
will not result in the production of any substance into the
environment.
V. 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 has concluded
that the rule does not contain policies that have federalism
implications as defined in the order and, consequently, a federalism
summary impact statement is not required.
List of Subjects in 21 CFR Part 310
Administrative practice and procedure, Drugs, Labeling, Medical
devices, Reporting and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
310 is amended as follows:
PART 310--NEW DRUGS
1. The authority citation for 21 CFR part 310 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360b-360f,
360j, 361(a), 371, 374, 375, 379e; 42 U.S.C. 216, 241, 242(a), 262,
263b-263n.
2. Section 310.545 is amended by adding paragraph (a)(6)(iv)(D), by
revising paragraph (d) introductory text, by adding and reserving
paragraph (d)(32), and by adding paragraph (d)(33) to read as follows:
Sec. 310.545 Drug products containing certain active ingredients
offered over-the-counter (OTC) for certain uses.
(a) * * *
(6) * * *
(iv) * * *
(D) Approved as of October 29, 2001. Any oral bronchodilator active
ingredient (e.g., ephedrine, ephedrine
[[Page 49278]]
hydrochloride, ephedrine sulfate, racephedrine hydrochloride, or any
other ephedrine salt) in combination with any analgesic(s) oranalgesic-
antipyretic(s), anticholinergic, antihistamine, oralantitussive, or
stimulant active ingredient.
* * * * *
(d) Any OTC drug product that is not in compliance with this
section is subject to regulatory action if initiallyintroduced or
initially delivered for introduction intointerstate commerce after the
dates specified in paragraphs(d)(1) through (d)(33) of this section.
* * * * *
(32) [Reserved]
(33) October 29, 2001, for products subject to paragraph
(a)(6)(iv)(D) of this section.
Dated: September 20, 2001.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 01-24127 Filed 9-26-01; 8:45 am]
BILLING CODE 4160-01-S