[Federal Register Volume 61, Number 98 (Monday, May 20, 1996)]
[Rules and Regulations]
[Pages 25142-25147]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-12499]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 310 and 341
[Docket No. 94N-0247]
RIN 0910-AA01
Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug
Products for Over-the-Counter Human Use; Amendment of Monograph for OTC
Bronchodilator Drug Products
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is amending the final
monograph for over-the-counter (OTC) bronchodilator drug products by
removing pressurized metered-dose aerosol container dosage forms for
the ingredients epinephrine, epinephrine bitartrate, and racepinephrine
hydrochloride. This action is being taken because the OTC marketing of
such drug products will require an approved application containing
certain information not required by the monograph. The agency is also
amending the regulation that lists nonmonograph active ingredients by
adding any ingredient(s) in a pressurized metered-dose aerosol
container for OTC bronchodilator drug products. This final rule is part
of the ongoing review of OTC drug products conducted by FDA.
EFFECTIVE DATE:June 19, 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 October 2, 1986 (51 FR 35326), FDA
issued a final monograph establishing conditions
[[Page 25143]]
under which OTC bronchodilator drug products are generally recognized
as safe and effective and not misbranded. Section 341.76(d)(2)(i) (21
CFR 341.76(d)(2)(i)) provides for products containing epinephrine,
epinephrine bitartrate, and racepinephrine hydrochloride for use in a
pressurized metered-dose aerosol container (hereinafter referred to as
an inhaler or MDI). The agency stated in the final monograph (51 FR
35326 at 35333 to 35334) that data and information available at that
time concerning the technology to produce reliable MDI dosage forms
allowed the agency to generally recognize OTC MDI drug products as safe
and effective. Further, the agency had anticipated that MDI drug
products would continue to contain a chlorofluorocarbon (CFC)
propellant and that marketing would continue under approved
applications, as stated in Sec. 2.125(d) (21 CFR 2.125(d)), containing
information on manufacturing controls for the MDI.
In the Federal Register of March 9, 1995 (60 FR 13014), FDA issued
a notice of proposed rulemaking to amend the final monograph for OTC
bronchodilator drug products to remove pressurized MDI aerosol
container dosage forms for the ingredients epinephrine, epinephrine
bitartrate, and racepinephrine hydrochloride. The agency also proposed
to amend the regulation that lists nonmonograph active ingredients to
add any ingredient(s) in a pressurized MDI aerosol container for OTC
bronchodilator drug products.
In the proposal, the agency discussed several developments that
changed its view about the inclusion of pressurized MDI dosage forms in
the final monograph for OTC bronchodilator drug products. The agency
determined that an assessment of the safety and effectiveness of each
MDI aerosol drug product must be made based on a reconsideration of the
nature of MDI aerosol drug products, potential future reformulations to
include new propellants, and the recommendations of various
international workshops and FDA advisory committee discussions. The
agency proposed that all MDI aerosol dosage forms must have premarket
approval to ensure their safety and effectiveness.
Interested persons were invited to file by May 23, 1995, written
comments or objections on the proposed regulation. Interested persons
were invited to file comments on the agency's economic impact
determination by May 23, 1995.
In response to the proposal, one drug manufacturer and an
association of pharmaceutical scientists submitted comments. Copies of
the comments are on public display in the Dockets Management Branch
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,
Rockville, MD 20857. Final agency action on OTC MDI aerosol drug
products containing epinephrine, epinephrine bitartrate, and
racepinephrine hydrochloride occurs with the publication of this final
rule amending the final monograph for OTC bronchodilator drug products.
As discussed in the proposal (60 FR 13014), the agency advised
that the conditions under which the drug products that are subject to
this amendment to the final monograph will no longer be generally
recognized as safe and effective and are misbranded (nonmonograph
conditions) will be effective 30 days after the date of publication in
the Federal Register. Therefore, on or after June 19, 1996, no OTC drug
product that is subject to the monograph and that contains a
nonmonograph condition, i.e., a condition that would cause the drug to
be not generally recognized as safe and effective or to be misbranded,
may be initially introduced or initially delivered for introduction
into interstate commerce unless it is the subject of an approved
application or abbreviated application (hereinafter called
application). Manufacturers are encouraged to comply voluntarily with
the final rule at the earliest possible date.
All ``OTC Volumes'' cited throughout this document refer to the
submissions made by interested persons pursuant to the call-for-data
notice published in the Federal Register of August 9, 1972 (37 FR
16029), or to additional information that has come to the agency's
attention since publication of the advance notice of proposed
rulemaking. The volumes are on public display in the Dockets Management
Branch.-
-II. The Agency's Conclusions on the Comments
One comment, from a pharmaceutical scientists' association, agreed
with the agency's proposal to amend the final monograph for OTC
bronchodilator drug products to remove MDI aerosol dosage forms for the
ingredients epinephrine, epinephrine bitartrate, and racepinephrine
hydrochloride. The comment also agreed that such products should have
premarket approval to ensure their safety and effectiveness. The
comment explained that changes in an MDI aerosol could have significant
effects on the distribution characteristics of the drug in the airways,
produce a pharmacological interaction, and/or enhance toxicity of the
drug product. With the phaseout of CFC-containing propellants in MDI
aerosol drug products, the comment mentioned that the safety and
effectiveness of the replacement propellants in these products will
need to be established.
The comment stated that appropriately focused and well-designed
clinical studies will be necessary to establish the clinical safety and
effectiveness of new non-CFC-containing MDI aerosol formulations. New
chemistry, manufacturing, and controls evaluations will be needed to
document that the new formulation is compatible with the bronchodilator
active ingredient and that drug delivery from the new system is
comparable to the old system. The comment added that much of the
testing needed to confirm the integrity and proper functioning of MDI
aerosol drug products containing non-CFC propellants can be determined
by in vitro testing. Such testing could determine particle size, total
canister contents, and consistency and reproducibility of dose delivery
through the life of the dosage form, as well as assess drug related
impurities and leakage rate.
The comment expressed some concern about epinephrine, epinephrine
bitartrate, and racepinephrine hydrochloride used in a hand-held rubber
bulb nebulizer. The comment stated that the agency's concerns about MDI
aerosol dosage forms, particularly changes in the distribution
characteristics of the drug in the airways, are equally applicable to
hand-held rubber bulb nebulizers and spraying devices currently
available. The comment also questioned the emphasis placed on many of
the comments and conclusions drawn by the authors of articles cited
within the proposed amendment because many of those references did not
provide details of the composition of MDI aerosol drug products
discussed. The comment did not specify which references failed to
provide sufficient details.
Another comment, from a drug manufacturer, disagreed with the
agency's proposal. The comment claimed that the proposal does not
provide a reasonable basis to support the revocation of the ``generally
recognized as safe and effective'' status of these OTC MDI aerosol drug
products. The comment contended that the proposal raises questions
about the safety and effectiveness of these drug products in the
absence of any data showing that epinephrine-containing MDI aerosol
drug products are not safe and effective when used according to
[[Page 25144]]
the labeling. The comment stated that the safety information discussed
in the proposal relates to MDI aerosol products containing albuterol,
and it does not raise any questions with respect to the safety of
epinephrine-containing MDI aerosol drug products. The comment argued
that because all CFC-containing MDI aerosol drug products must now be
the subject of an approved new drug application (NDA), there is no
public health issue concerning these drug products and, therefore, no
need for this proposed monograph amendment.
The comment added that in the final monograph for OTC
bronchodilator drug products (51 FR 35326 at 35333), the agency
recognized that manufacturer compliance with FDA's current good
manufacturing practice (CGMP) regulations would adequately address the
control of the quality of drug product containers, components, and the
drug product itself, and that specific requirements for MDI aerosol
drug delivery systems in the monograph were unnecessary. The comment
indicated that while CGMP compliance is important to assure the proper
use of MDI aerosol delivery systems, the proposed amendment provides no
evidence that CGMP compliance is a concern for currently-marketed
epinephrine MDI aerosols.
The comment agreed with the agency that non-CFC propellants could
render an MDI aerosol product a ``new drug'' under Sec. 310.3(h)(1) (21
CFR 310.3(h)(1)). In that case, additional data would be required to
support safety and effectiveness. However, the comment argued that new
propellant formulations can be reviewed under an NDA without revoking
the OTC monograph status of currently marketed CFC-containing MDI
aerosol formulations.
The comment mentioned that the proposal to remove OTC MDI aerosol
drug products from the final monograph for OTC bronchodilator drug
products is not based on the deliberations of any advisory committee
and is in conflict with the determination of the Advisory Review Panel
on OTC Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug
Products that epinephrine-containing OTC MDI aerosol drug products are
``generally recognized as safe and effective.'' The comment stated that
the agency should withdraw the proposal until such time as an advisory
committee has reviewed the data and voted on a recommendation.
The comment also expressed concern that the agency's action could
unnecessarily raise the data burden of NDA's for epinephrine-
containing, CFC-propelled MDI's by imposing, without justification, new
safety and effectiveness data requirements that are satisfied by the
current monograph status. The comment noted that in Sec. 330.11 (21 CFR
330.11), if an OTC drug product meets all the conditions of an
applicable monograph, only a review of information pertaining to
deviations from those conditions is necessary. The comment contended
that Sec. 330.11 encourages innovation and improvement in the
pharmaceutical industry without unnecessary regulatory delays and
unjustified data burdens. The comment added that, if new NDA's need to
be submitted, the additional data required could have the effect of
forcing from the market a product that has been the subject of an
approved NDA and has had a safe marketing history for many years.
Therefore, for these reasons, the comment requested that the agency
withdraw the proposed amendment and take no further steps to complete
this rulemaking.
The agency has considered the information presented by the
comments and determined that marketing of pressurized MDI aerosol
bronchodilator drug products containing CFC propellants requires an
approved NDA containing information beyond that required by the final
monograph for OTC bronchodilator drug products. Since publication of
that final monograph in 1986, the agency has reconsidered the nature of
MDI aerosol drug products, potential future reformulations to include
new propellants, and the recommendations of various international
organizations and agency advisory committees concerning the regulatory
and data requirements needed to assure the clinical community and
patients of the safety and effectiveness of MDI aerosol drug products.
In the proposed monograph amendment (60 FR 13014 to 13020), the
agency discussed several specific developments that have changed its
views about MDI aerosol dosage forms. These included: (1) Recent
publications reporting chemistry, manufacturing, and controls problems
resulting from changes to the container and closure system of
redesigned MDI aerosol dosage forms; (2) the need for safety and
effectiveness data for the new drug products as a result of those
chemistry, manufacturing, and controls changes; (3) international
workshops and FDA advisory committee discussions focusing on regulatory
requirements for modifications to an approved innovator MDI and
bioequivalence of generic MDI aerosol drug products; (4) legislation
that requires a phaseout of ozone-depleting substances, including CFC
propellants in MDI aerosol drug products; and (5) the need for safety
data on the alternative propellants that will replace CFC's in MDI
aerosol dosage forms, as well as evidence that the new MDI's deliver
the drug effectively.
The agency's decision to remove epinephrine ingredients in
pressurized MDI aerosol dosage forms from the final monograph for OTC
bronchodilator drug products is not based on a specific safety or
effectiveness concern that has been identified for any of the currently
marketed OTC MDI aerosol drug products. All such products are currently
the subject of an approved NDA based on agency regulations in
Sec. 2.125(d). The removal of these OTC drug products from the
monograph is being done to ensure continued safety and effectiveness of
these products and to provide a regulatory basis for adequate
regulation of the manufacture of all future OTC MDI aerosol drug
products, including those with the new propellants. This action is
based on the agency's increased awareness that minor modifications in
the manufacturing procedures of these products and the proposed
phaseout of CFC propellants have the potential for substantial impact
on the safety and effectiveness of these OTC drug products and are not
adequately addressed by CGMP guidelines.
In response to the comment regarding the ``generally recognized as
safe and effective'' status of currently marketed OTC MDI aerosol drug
products containing epinephrine, epinephrine bitartrate, and
racepinephrine hydrochloride, the agency maintains that its
preclearance of these products under NDA's alleviates concerns about
the safety and effectiveness of these drug products. However, the
agency now considers preclearance of the manufacturing processes of
these products an important part of assuring their continued safe and
effective use.
The agency points out that the safety information discussed in the
proposal relates not only to MDI aerosol drug products containing
albuterol, but to all such products in pressurized MDI dosage form.
Recent data presented to the agency indicate that variability in the
performance of an MDI aerosol may result from the physical
characteristics of the drug substance, formulation differences, valve
and actuator design, and the adequacy of control parameters,
specifications, and test methods for each component and the final drug
product. Design modification of any component of the drug product may
result in significant alterations of the dose delivered to the lung. In
addition,
[[Page 25145]]
changes in the source or the composition of the drug product may
introduce unknown contamination or impurities (extractables) when the
propellant comes in contact with the plastic or rubber components of
the canister (Ref. 1).
Because all currently marketed OTC CFC-containing MDI aerosols
containing epinephrine are the subject of approved applications, the
agency does not agree with one comment that this monograph amendment
will require additional data or new applications to support the safety
and effectiveness of these bronchodilator drug products. Based on
agency preclearance under existing applications, the safety and
effectiveness of currently marketed OTC MDI drug products are not in
question. However, the agency does consider it necessary that OTC
marketing of new or reformulated MDI aerosol drug products or products
manufactured by a different manufacturer or in a different facility
require preclearance via an approved application containing information
not required by the monograph to assure the continued safe and
effective use of these drug products.
An NDA deviation (Sec. 330.11) applies to products whose
ingredient(s) is included in an OTC drug monograph. OTC MDI aerosol
drug products already require an NDA for marketing because of the CFC
propellants (Sec. 2.125(d)). A change in manufacturing procedures may
only require a supplement to an NDA. If a change in manufacturing
facilities occurs or a product is manufactured by a different company,
the affected manufacturer should consult with the agency to ascertain
what will be required in the supplemental application.
In the proposed amendment (60 FR 13014 at 13018), the agency cited
several international workshops and agency advisory committee
discussions that identified the regulatory requirements necessary to
determine the safety and effectiveness of reformulated bronchodilator
drug products. The Commission of the European Communities, the Drug
Information Association, and the agency's Generic Drugs Advisory
Committee with representatives from the Pulmonary-Allergy Drugs
Advisory Committee (Refs. 2, 3, and 4, respectively) agreed that any
change in excipients (including propellants) might result in changes in
drug deposition patterns within the lung and might affect absorption
and systemic safety. Further, these organizations and committees stated
that premarket approval is essential to ensure the identity, strength,
quality, and purity of pressurized OTC and prescription bronchodilator
drug products.
In response to some of the comment's concerns regarding the use of
ephinephrine, epinephrine bitartrate, and racepinephrine hydrochloride
in hand-held rubber bulb nebulizers, the agency agrees that some of
these concerns about MDI aerosol dosage forms, particularly changes in
the distribution characteristics of the drug in the airways, are
equally applicable to hand-held rubber bulb nebulizers and spraying
devices. The agency intends to reexamine the use of these OTC
bronchodilator drugs in hand-held rubber bulb nebulizers in a future
issue of the Federal Register.
The agency does not agree with one comment that this amendment
should be withdrawn until an advisory committee has provided its
recommendation. As stated earlier, the agency is not questioning the
safety and effectiveness of currently marketed OTC MDI aerosol drug
products. However, the agency considers it necessary to review and
evaluate the manufacturing controls for these drug products to assure
their continued safe and effective use. This monograph amendment deals
with process issues (the procedure by which the product gets on the
market or how manufacturing changes occur), and in this particular case
the agency does not consider it necessary to bring this amendment to an
advisory committee for deliberation. However, in some cases, it may be
appropriate to bring procedural issues to an advisory committee.
In the proposed monograph amendment (60 FR 13014 at 13020), the
agency indicated that there is a statutory phaseout of CFC propellants
used in these MDI aerosol products, although an exemption for MDI's for
the treatment of asthma and chronic obstructive pulmonary disease
exists through 1997. Based on the intended phaseout of CFC-containing
propellants in MDI aerosol dosage forms, the agency is aware that the
pharmaceutical and other industries are investigating alternative
propellants to replace CFC's in MDI's. Given the complexity of MDI
aerosol formulations and the interdependence of each of the MDI
components, the agency is concerned that the use of new excipients,
including non-CFC-containing propellants, could change the distribution
characteristics of the MDI bronchodilator drug in the airways, produce
a pharmacological interaction, or enhance toxicity of the active drug
substance. Such changes in MDI aerosol formulations might alter
pulmonary absorption, potentially resulting in changes in the safety
and/or therapeutic effectiveness of the bronchodilator drug product.
Thus, the agency intends to require manufacturers who reformulate
currently approved MDI aerosol drug products with new propellants to
submit additional data or a new NDA to demonstrate that inhalation and
ingestion of new formulations will not result in local tissue
irritation effects or other undesirable consequences, such as loss of
effectiveness or local retention, resulting from inappropriate drug
deposition characteristics. The additional data must include an
assessment of the absorption, distribution, and retention
characteristics of new propellant systems in man following inhalation.
Drug deposition profiles including the quantity of drug reaching the
respiratory airways and its depth of penetration must also be
characterized.
Based on the above discussion, the agency considers it essential
that any reformulated MDI aerosol (including use of a new propellant or
component design alterations) have premarket approval under an approved
NDA to ensure the safety and effectiveness of the bronchodilator drug
product. Therefore, the agency is removing the ingredients epinephrine,
epinephrine bitartrate, and racepinephrine hydrochloride in pressurized
MDI aerosol dosage forms from the final monograph for OTC
bronchodilator drug products because such products will continue to
require an approved NDA containing certain information not required by
the monograph. However, the monograph status of these ingredients when
used in a hand-held rubber bulb nebulizer is not changed. Such products
will remain in the final monograph at this time.
III. References
The following references are on display in the Dockets Management
Branch (address above) and may be seen by interested persons between 9
a.m. and 4 p.m., Monday through Friday.
(1) Adams, W. P. et al., ``Regulatory Aspects of Modifications
to Innovator Bronchodilator Metered Dose Inhalers and Development of
Generic Substitutes,'' Journal of Aerosol Medicine, 7:119-134, 1994.
-(2) ``Report of the Commission of the European Communities'
Committee for Proprietary Medicinal Products, Matters Relating to
the Replacement of CFCs in Medicinal Products,'' December 15, 1993,
in OTC Vol. 04BFMA3.
-(3) Drug Information Association, MDI's in the Milennium:
Workshop on Regulatory Issues of Efficacy, Safety, and Quality with
Metered Dose Inhalers (MDI's) Drug Dosage Forms, October 18 and 19,
1993, in OTC Vol. 04BFMA3.-
(4) Transcripts of the FDA Generic Drugs Advisory Committee
Meeting with
[[Page 25146]]
Pulmonary-Allergy Drugs Advisory Committee Representation, September
14 and 15, 1993, identified as TS, Docket No. 94N-0247, Dockets
Management Branch.
-IV. The Agency's Final Conclusions
In this amendment, the agency is removing the ingredients
epinephrine, epinephrine bitartrate, and racepinephrine hydrochloride
in pressurized MDI aerosol dosage forms from the final monograph for
OTC bronchodilator drug products. Accordingly, the agency is amending
Sec. 341.76(d)(2) to remove Sec. 341.76(d)(2)(i)(a) and (d)(2)(i)(b).
The agency is also amending Sec. 310.545(a)(6)(iv) for bronchodilator
drug products by adding new paragraph (a)(6)(iv)(C) and listing
thereunder ``any ingredient(s) in a pressurized metered-dose aerosol
container.'' In addition, the agency is removing Sec. 341.76(e) from
the final monograph because that information now appears in
Sec. 330.1(i) (21 CFR 330.1(i)) as part of the general labeling policy
for OTC drug products.
The agency points out that incorrect dates were inadvertently
inserted in Sec. 310.545(a)(6)(iv)(C) and (d)(26) of the proposed
amendment (60 FR 13014 at 13020). Consequently, the agency is revising
the dates in these sections to indicate that the conditions of this
final rule will be effective 30 days after the date of publication in
the Federal Register. Further, proposed Sec. 310.545(d)(26) is
renumbered in this final rule as Sec. 310.545(d)(25).
-V. Analysis of Impacts
The agency received one comment in response to the agency's
request for comments on any substantial or significant economic impact
that this rulemaking would have on OTC bronchodilator MDI aerosol drug
products that contain epinephrine, epinephrine bitartrate, and
racepinephrine hydrochloride (60 FR 13014 at 13020). The comment
indicated that this rulemaking would have a significant impact on the
OTC bronchodilator industry and itself if additional data or new NDA's
were requested for existing NDA-approved MDI aerosol drug products. As
discussed above, this monograph amendment should have minimal impact on
any existing MDI aerosol drug product marketed under an approved NDA.
Any changes in manufacturing procedures will require a standard
supplemental application that would have been required before the
amendment was finalized.
FDA has examined the impacts of this 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 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 Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. This monograph amendment does not change the status
of any currently marketed MDI aerosol drug products. All such products
are currently the subject of an approved application. As is currently
the case for marketed MDI aerosol products, in the interest of public
health and safety, an approved application will be required for any
product that is reformulated to contain a non-CFC propellant. In
addition, there are a limited number of MDI aerosol bronchodilator drug
product manufacturers. 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.
-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
21 CFR Part 310
Administrative practice and procedure, Drugs, Labeling, Medical
devices, Reporting and recordkeeping requirements.
21 CFR Part 341
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
parts 310 and 341 are amended as follows:
-PART 310--NEW DRUGS
1. The authority citation for 21 CFR part 310 continues to read as
follows:
Authority: Secs. 201, 301, 501, 502, 503, 505, 506, 507, 512-
516, 520, 601(a), 701, 704, 705, 721 of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 357,
360b-360f, 360j, 361(a), 371, 374, 375, 379e); secs. 215, 301,
302(a), 351, 354-360F of the Public Health Service Act (42 U.S.C.
216, 241, 242(a), 262, 263b-263n).
2. Section 310.545 is amended by adding new paragraphs
(a)(6)(iv)(C) and (d)(25) and by revising paragraph (d) introductory
text to read as follows:
Sec. 310.545 Drug products containing certain active ingredients
offered over-the-counter (OTC) for certain uses.
(a) * * *
(6) * * *
(iv) Bronchodilator drug products.
* * *
(C) Approved as of June 19, 1996. Any ingredient(s) in a
pressurized metered-dose inhaler container.
* * * * *
(d) Any OTC drug product that is not in compliance with this
section is subject to regulatory action if initially introduced or
initially delivered for introduction into interstate commerce after the
dates specified in paragraphs (d)(1) through (d)(25) of this section.
* * * * *
(25) June 19, 1996, for products subject to paragraph
(a)(6)(iv)(C) of this section.
-PART 341--COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC
DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE
3. The authority citation for 21 CFR part 341 continues 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).
Sec. 341.76 [Amended]
4. Section 341.76 is amended by removing paragraphs (d)(2)(i) and
(e), redesignating paragraph (d)(2)(ii) as paragraph (d)(2), and
revising the heading of newly redesignated paragraph (d)(2) to read as
follows:
Sec. 341.76 Labeling of bronchodilator drug products.
-* * * * *
(d) * * *
-(2) For products containing epinephrine, epinephrine bitartrate,
and racepinephrine hydrochloride identified
[[Page 25147]]
in Sec. 341.16(d), (e), and (g) for use in a hand-held rubber bulb
nebulizer.
* * *
Dated: April 11, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-12499 Filed 5-17-96; 8:45 am]
BILLING CODE 4160-01-F