[Federal Register Volume 71, Number 147 (Tuesday, August 1, 2006)]
[Rules and Regulations]
[Pages 43358-43363]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-12265]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 341
[Docket No. 1976N-0052N] (formerly 76N-052N)
RIN 0910-AF34
Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug
Products for Over-the-Counter Human Use; Amendment of Monograph for OTC
Nasal Decongestant Drug Products
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
to amend the final monograph (FM) for over-the-counter (OTC) nasal
decongestant drug products (drug products used to relieve nasal
congestion due to a cold, hay fever, or other upper respiratory
allergies) to add phenylephrine bitartrate (PEB), both individually and
in combination drug products in an effervescent dosage form, as
generally recognized as safe and effective (GRASE). An effervescent
dosage form is intended to be dissolved in water before taking by
mouth. This final rule is part of FDA's ongoing review of OTC drug
products.
DATES: Effective Date: This rule is effective August 31, 2006.
FOR FURTHER INFORMATION CONTACT: Michael T. Benson, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, rm. 5484, Silver Spring, MD 20993, 301-796-
2090.
SUPPLEMENTARY INFORMATION:
I. Background
A. Advance Notice of Proposed Rulemaking (ANPR)
1. OTC Cough-Cold Drug Products
In the Federal Register of September 9, 1976 (41 FR 38312), FDA
published the report of the Advisory Review Panel on OTC Cold, Cough,
Allergy, Bronchodilator, and Antiasthmatic Drug Products (Cough-Cold
Panel). That Panel reviewed oral and topical nasal decongestant drug
products and found several active ingredients, including phenylephrine
hydrochloride (PEH), to be safe and effective ingredients for OTC use
(41 FR 38312 at 38399 and 38400). The Cough-Cold Panel did not evaluate
PEB.
[[Page 43359]]
2. OTC Oral Health Care Drug Products
In the Federal Register of May 25, 1982 (47 FR 22760), FDA
published the report of the Advisory Review Panel on OTC Oral Cavity
Drug Products (Oral Cavity Panel). That Panel reviewed the safety and
effectiveness of two oral nasal decongestant ingredients, PEH and
phenylpropanolamine hydrochloride (both in lozenge form for topical
use), and classified these ingredients as Category III (more
effectiveness data needed) (47 FR 22760 at 22911 through 22914). The
Oral Cavity Panel did not evaluate PEB.
B. Tentative Final Monograph (TFM)
1. OTC Cough-Cold Drug Product
In the Federal Register of January 15, 1985 (50 FR 2220), FDA
published the TFM for OTC nasal decongestant drug products. The TFM
proposed PEH as a monograph ingredient, but PEB was not addressed due
to lack of available data.
2. OTC Oral Health Care Drug Products
In the Federal Register of January 27, 1988 (53 FR 2436), FDA
published the TFM for OTC oral health care (anesthetic/analgesic,
astringent, debriding agent/oral wound cleanser, and demulcent) drug
products. FDA referred the data on the oral nasal decongestant
ingredients PEH and phenylpropanolamine hydrochloride in lozenge form
for topical use to the rulemaking for OTC nasal decongestant drug
products, because that was the primary rulemaking for these ingredients
(53 FR 2436 at 2448 and 2449).
C. Final Monograph (FM) OTC Cough-Cold Drug Products
In the Federal Register of August 23, 1994 (59 FR 43386), FDA
published the FM for OTC nasal decongestant drug products. The
monograph included PEH as GRASE for oral and topical use as a nasal
decongestant (21 CFR 341.20(a)(1) and (b)(8)). The monograph did not
specify specific oral dosage forms. FDA acknowledged that PEB was
submitted as an oral nasal decongestant active ingredient in an
effervescent combination tablet for OTC use. FDA noted that PEB was not
reviewed by the Cough-Cold Panel, or included in its report, and was
not addressed in the FM for OTC nasal decongestant drug products (59 FR
43386 at 43394 and 43395). FDA reviewed data on PEB submitted in a
comment and concluded that the data were inadequate to demonstrate the
safety and effectiveness of PEB in an effervescent dosage form as an
OTC oral nasal decongestant ingredient. Consequently, this ingredient
was not included in the FM.
On March 20, 2002, a manufacturer submitted a citizen petition to
amend the OTC nasal decongestant FM to include the ingredient PEB in an
effervescent tablet as GRASE for use as a single ingredient or in
combination with any monograph cough-cold active ingredient. The
petition included:
Domestic and international marketing experience to meet
FDA's material time and extent criteria for inclusion in an OTC drug
monograph (see 21 CFR 330.14)
In vitro and in vivo studies to demonstrate comparability
of PEB with PEH, an approved monograph active ingredient
A proposal that PEB would provide consumers with greater
choice in combination nasal decongestant/analgesic cough-cold
formulations
In the Federal Register of November 2, 2004 (69 FR 63482), FDA
published a proposed rule to amend the FM for OTC nasal decongestant
products to add PEB in an effervescent tablet as a single ingredient or
in combination with aspirin and chlorpheniramine maleate. A drug
manufacturer and an individual submitted comments, which included
several issues that are discussed in section II of this document.
II. The Agency's Conclusion on the Comments
(Comment 1) One comment asked FDA to expand the definition of an
effervescent dosage form. FDA had proposed the following definition for
an effervescent tablet: ``A tablet intended to be dissolved in water
before administration. It contains, in addition to the active
ingredient(s), mixtures of acids (citric acid, tartaric acid) and
sodium bicarbonate, which releases carbon dioxide when dissolved in
water.''
The comment requested that FDA revise the proposed definition of
effervescent tablet to permit additional inactive ingredients, claiming
that its suggested revision would provide greater formulation
flexibility. The comment based its revised definition upon definitions
from pharmaceutical texts and reference books, including the United
States Pharmacopeia (U.S.P.), the British/European Pharmacopeia (BP/
EP), and other pharmacopeial individual monographs. The comment
requested that FDA revise the definition of effervescent tablet as
follows: ``A tablet intended to be dissolved or dispersed in water
before administration. It generally contains, in addition to the active
ingredient(s), mixtures of acids/acid salts (citric acid, tartaric
acid, malic acid, or any other suitable acid or acid anhydride), which
release carbon dioxide when mixed with water. Occasionally, the active
ingredient itself could act as the acid or alkali metal compound
necessary for effervescent reaction.''
FDA declines the request to revise the definition of effervescent
tablet to permit additional inactive ingredients, but is expanding the
definition in a different manner to provide manufacturers greater
formulation flexibility. FDA's definition in the OTC nasal decongestant
FM is substantially the same as the definitions for effervescent
tablets in the U.S.P. (Ref. 1) and for effervescent tablets and
granules in the FDA Center for Drug Evaluation and Research (CDER) Data
Standards Manual (Ref. 2). All of these definitions describe a dosage
form that contains citric acid, tartaric acid, and sodium bicarbonate
as inactive ingredients to produce the effervescence, and the product
releases gas (carbon dioxide) when added to water.
FDA is not revising the definition in the manner suggested by the
comment because the agency has concerns about the comment's proposed
use of the term ``any other suitable acid or acid anhydride.'' This
term is not sufficiently specific to ensure consistency with the
current regulatory requirements for inactive ingredients. Under Sec.
330.1(e) (21 CFR 330.1(e)), a product is required to contain only
suitable inactive ingredients that meet certain criteria. These
inactive ingredients must be safe in the amounts administered and must
not interfere with the effectiveness of the preparation or with
suitable tests or assays to determine if the product meets its
professed standards of identity, strength, quality, and purity. The
comment did not submit data to demonstrate that the additional inactive
ingredients it requests are safe in the amounts administered or that
they do not interfere with the effectiveness of the preparation or with
suitable tests or assays. FDA is not aware of any such data for
effervescent dosage forms that contain PEB. FDA is also not aware of
PEB as the active ingredient in these products acting as ``the acid or
alkali metal compound necessary for effervescent reaction.''
Accordingly, FDA is not adding this requested information to the
definition at this time.
Interested parties should contact U.S.P. for any change in the
compendial definition of an effervescent tablet that would apply to all
such products. The definition in Sec. 341.3(i) applies only to
products containing PEB covered by this FM. Interested parties who wish
to
[[Page 43360]]
include a PEB effervescent dosage form that contains different inactive
ingredients than those listed in the definition in this FM may provide
FDA specific data on such a product
FDA is expanding the definition of ``effervescent tablet'' by
replacing ``effervescent tablet'' in Sec. 341.3(i) of the proposed
rule with ``effervescent dosage form'' in this final rule. We are
making this change to provide greater formulation flexibility to permit
other effervescent dosage forms (e.g., granules and powders) to be
marketed. The FDA CDER Data Standards Manual (Ref. 2) defines an
effervescent granule as ``a small particle or grain containing a
medicinal agent in a dry mixture * * *.'' The pharmacokinetic data
provided for the PEB effervescent tablet dosage form would also support
use of an effervescent granule or powder dosage form, based on the
smaller particle size of these dosage forms. Accordingly, the
definition in Sec. 341.3(i) now reads: ``Effervescent dosage form. A
dosage form intended to be dissolved in water before administration. It
contains, in addition to the active ingredient(s), mixtures of acids
(citric acid, tartaric acid) and sodium bicarbonate, which release
carbon dioxide when dissolved in water.'' In conjunction with this
change, we have also changed the proposed active ingredient description
``phenylephrine bitartrate effervescent tablet'' in Sec. 341.20(a)(4)
to ``phenylephrine bitartrate effervescent dosage form'' in this FM.
(Comment 2) One comment requested FDA to allow PEB as an oral nasal
decongestant in all combination products containing an oral nasal
decongestant when formulated as an effervescent tablet and labeled in
accordance with 21 CFR 341.80 and 21 CFR 341.85. The comment contended
that PEH is included as a GRASE oral nasal decongestant ingredient in
the monograph for OTC Cold, Cough, Allergy, Bronchodilator, and
Antiasthmatic Drug Products and is included in 17 permitted
combinations. The comment further stated that FDA acknowledged in the
proposed rule that both phenylephrine salts (bitartrate and
hydrochloride) have similar safety and efficacy profiles, and could be
used in effervescent tablets interchangeably without any clinically
significant impact on the performance of the formulations studied. The
comment provided in-vitro data demonstrating comparable recovery of the
active ingredient following dissolution in various solution media of
effervescent tablets formulated with either PEH or PEB, in the presence
or absence of other common cough/cold active ingredients.
FDA agrees with the comment. In the Federal Register of January 15,
1985 (50 FR 2220), FDA affirmed the Cough-Cold Panel recommendations
for numerous combinations containing an oral nasal decongestant and
other active ingredients. PEH was one of those active ingredients. In
the proposed rule of the current rulemaking (69 FR 63482 at 63485,
November 2, 2004), FDA acknowledged that the two phenylephrine salts in
effervescent tablets could be used interchangeably. The similarity in
the rate and extent of absorption of PEH and PEB in the effervescent
tablets allows FDA to conclude that the bioavailability of the
phenylephrine salts in the effervescent tablets is comparable (69 FR
63482, November 2, 2004). With regard to PEB and other combinations:
PEH is similarly bioavailable to PEB, as stated
previously, and in-vitro dissolution data demonstrate that recovery of
phenylephrine from formulations of either salt is virtually
indistinguishable (PEH v PEB). FDA believes that PEB would have also
been among the ingredients recommended for inclusion in the same
combinations as PEH, had the Cough-Cold Panel considered that
ingredient. Accordingly, FDA is including PEB in an effervescent dosage
form as a permitted active ingredient as follows:
In the same types of combination products as the other
oral nasal decongestant active ingredients under Sec. Sec. 341.40 (b),
(c), (e), (g), (i), (j), (m), (n), (p), (q), (r), (s), (t), (x), (y),
(aa), and (bb),
With labeling for combination products under Sec. 341.85
(b)(1), (b)(2), (b)(3), and (c)(3).
(Comment 3) One comment contended that FDA should not approve PEB
for OTC use until an official compendium exists to define the quality
and purity of its effervescent dosage form. FDA does not agree with the
comment's suggestion. PEB as a drug substance became official in the
U.S.P. on August 1, 2005 (Ref. 3). FDA's regulation in 21 CFR 330.14(i)
sets forth criteria and procedures for classifying OTC drugs as GRASE
and not misbranded. It states that ``any active ingredient or botanical
drug substance included in a final OTC drug monograph * * * must be
recognized in an official USP-NF drug monograph that sets forth its
standards of identity, strength, quality, and purity.'' While FDA's
regulation mentions a U.S.P.-N.F. drug monograph for the active
ingredient, it does not also require a U.S.P.-N.F. drug monograph for
the active ingredient in a specific dosage form. Accordingly, FDA
concludes that a U.S.P. compendial monograph for the PEB drug substance
is a sufficient basis for including PEB as an active ingredient in an
effervescent tablet or other effervescent dosage form in the FM for OTC
nasal decongestant drug products.
III. Submission of Pharmacokinetic Data for Other Solid Dosage Forms of
PEB
FDA notes in the proposed rule that the rate and extent of
absorption after the first dose of PEB capsules are not similar to PEH
capsules. FDA is willing to consider pharmacokinetic data in support of
other PEB solid dosage forms (e.g., capsule, or noneffervescent tablet,
granule, or powder) and invites interested persons to submit such data
in the form of a petition under 21 CFR 10.30 to amend the monograph for
OTC nasal decongestant drug products.
IV. Labeling Change from the Proposed Rule
At the time of the proposed rule, sinusitis would have been a
permitted indication for OTC combination drug products that include PEB
in an effervescent dosage form as an oral nasal decongestant.
Subsequently, FDA revised the labeling for these products. In the
Federal Register of October 11, 2005 (70 FR 58974), FDA published a
final rule to eliminate the term ``sinusitis'' from the labeling of OTC
nasal decongestant drug products. Accordingly, FDA has revised the
introductory language of Sec. Sec. 341.85(b)(2) and (b)(3) of the
proposed rule to replace the term ``sinusitis'' with ``nasal
congestion.'' Sections 341.85(b)(2) and (b)(3) of the final rule now
read as follows:
``Sec. 341.85 Labeling of permitted combinations of active
ingredients.
(b)(2) For permitted combinations containing an analgesic-
antipyretic active ingredient * * * when labeled for relief of hay
fever/allergic rhinitis and/or nasal congestion symptoms.
(b)(3) For permitted combinations containing an oral analgesic-
antipyretic active ingredient * * * when labeled for relief of general
cough-cold symptoms and/or the common cold and for relief of hay fever/
allergic rhinitis and/or nasal congestion symptoms.''
V. Summary of Agency Changes
1. FDA is changing the definition of ``effervescent tablet'' in
Sec. 341.3(i) to ``effervescent dosage form.'' In conjunction with
this change, FDA is changing the active ingredient description in Sec.
341.20(a)(4) from ``Phenylephrine bitartrate in an effervescent
tablet'' to ``Phenylephrine bitartrate in an effervescent dosage
[[Page 43361]]
form'' (see section II, comment 1 of this document).
2. In the proposed rule, FDA proposed to amend Sec. 341.40(b),
(c), (e), (g), (i), (j), (m), (n), (p), (q), (r), (s), (t), (x), (y),
(aa), and (bb) to exclude PEB in Sec. 341.20(a)(4). Now that FDA is
allowing PEB in all of these combinations, there is no need to amend
these paragraphs because the existing language therein already refers
to all nasal decongestant active ingredients in Sec. 341.20(a).
3. FDA is eliminating proposed Sec. 341.40 (cc) because the
combination is now covered by Sec. 341.40(c). With the elimination of
proposed Sec. 341.40(cc), the proposed amendments of the headings in
Sec. 341.85(a)(1), (b)(1), (b)(2), (b)(3), and (c)(3) to add Sec.
341.40(cc) are no longer needed and are withdrawn. However, the
headings in Sec. 314.85(b)(2) and (b)(3) are being revised as
discussed in section IV of this document.
VI. Analysis of Impacts
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 (Public Law 104-4). 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 the 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 enacting any rule that may result in an expenditure
in any one year by state, local, and tribal governments, in the
aggregate, or by private sector, of $100 million (adjusted annually for
inflation).
FDA believes that this final rule is consistent with the principles
set out in Executive Order 12866 and in these two statutes. This 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, 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 of 1995 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 threshold after adjustment for inflation is $115 million, using
the most current (2003) Implicit Price Deflator for the Gross Domestic
Product.
The purpose of this final rule is to include PEB in the monograph
for OTC nasal decongestant drug products. This final rule will allow
manufacturers who market products containing this ingredient in foreign
countries and manufacturers who would like to market products
containing this ingredient in the United States to enter the market
place under the OTC drug monograph instead of a new drug application
(NDA). Cost savings will occur from marketing without an NDA.
Marketing a new OTC drug product containing PEB is optional for any
interested manufacturer. The costs would involve the standard startup
costs associated with marketing any new product under an OTC drug
monograph. Manufacturers will not incur any costs determining how to
state the product's labeling because the monograph amendment provides
that information. This final rule is not expected to require any new
reporting and recordkeeping activities. Therefore, no additional
professional skills will be needed.
FDA considered but rejected the option of not including PEB in the
monograph because it considers the data presented supportive of
monograph status. The ingredient became official in the U.S.P. on
August 1, 2005 (Ref. 3).
This analysis shows that FDA has considered the burden to small
entities. FDA does not consider an exemption for small entities
necessary because those manufacturers can enter the market place like
larger entities anytime after this FM becomes effective. 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)).
VII. 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
monograph labeling is 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)).
VIII. 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.
IX. Federalism
FDA has analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. FDA has determined that the rule
will have a preemptive effect on State law. Section 4(a) of the
Executive order requires agencies to ``construe * * * a Federal statute
to preempt State law only where the statute contains an express
preemption provision or there is some other clear evidence that the
Congress intended preemption of State law, or where the exercise of
State authority conflicts with the exercise of Federal authority under
the Federal statute.'' Section 751 of the Federal Food, Drug, and
Cosmetic Act (the act) (21 U.S.C. 379r) is an express preemption
provision. Section 751(a) of the act (21 U.S.C. 379r(a)) provides that:
``* * * no State or political subdivision of a State may establish or
continue in effect any requirement-- * * * (1) that relates to the
regulation of a drug that is not subject to the requirements of section
503(b)(1) or 503(f)(1)(A); and (2) that is different from or in
addition to, or that is otherwise not identical with, a requirement
under this Act, the Poison Prevention Packaging Act of 1970 (15 U.S.C.
1471 et seq.), or the Fair Packaging and Labeling Act (15 U.S.C. 1451
et seq.).'' Currently, this provision operates to preempt States from
imposing requirements related to the regulation of nonprescription drug
products. (See Section 751(b) through (e) of the act for the scope of
the express preemption provision, the exemption procedures, and the
exceptions to the provision.) This final rule would add PEB,
individually and in combination drug products when used in effervescent
dosage form, to the FM for OTC nasal decongestant drug products.
Although this final rule would have a preemptive effect, in that it
would preclude States from promulgating requirements related to these
PEB drug products that are different from or in addition to, or not
otherwise identical with a requirement in the final rule, this
preemptive effect is consistent with what Congress set forth in section
751 of the act. Section 751(a) of the act
[[Page 43362]]
displaces both State legislative requirements and State common law
duties. We also note that even where the express preemption provision
is not applicable, implied preemption may arise. See Geier v. American
Honda Co., 529 US 861 (2000).
FDA believes that the preemptive effect of the final rule would be
consistent with Executive Order 13132. Section 4(e) of the Executive
order provides that ``when an agency proposes to act through
adjudication or rulemaking to preempt State law, the agency shall
provide all affected State and local officials notice and an
opportunity for appropriate participation in the proceedings.'' FDA
provided the States with an opportunity for appropriate participation
in this rulemaking when it sought input from all stakeholders through
publication of the proposed rule in the Federal Register of November 2,
2004 (69 FR 63482). FDA received no comments from any States on the
proposed rulemaking.
In addition, on June 19, 2006, FDA's Division of Federal and State
Relations provided notice via fax and email transmission to elected
officials of State governments and their representatives of national
organizations. The notice provided the States with further opportunity
for comment on the rule. It advised the States of the publication of
the proposed rule and encouraged State and local governments to review
the notice and to provide any comments to Docket No. 1976N-0052N,
opened in the November 2, 2004, Federal Register notice, by a date 30
days from the date of the notice (i.e., by July 19, 2006), or to
contact certain named individuals. FDA received no comments in response
to this notice. The notice has been filed in Docket No. 1976N-0052N.
In conclusion, FDA believes that it has complied with all of the
applicable requirements under the Executive order and has determined
that the preemptive effects of this rule are consistent with Executive
Order 13132.
X. Effective Date
This final rule becomes effective August 31, 2006.
XI. References
The following references are on display in the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
rm. 1061, Rockville, MD 20852 under Docket No. 1976N-0052N and may be
seen by interested persons between 9 a.m. and 4 p.m., Monday through
Friday. (FDA has verified the Web site address, but is not responsible
for subsequent changes to the Web site after this document publishes in
the Federal Register.)
1. The United States Pharmacopeia 29-National Formulary 24, The
United States Pharmacopeial Convention, Inc., Rockville, MD, pp
3005, 2006.
2. CDER Data Standards Manual (see sections entitled ``Tablet
Effervescent'' and ``Granule Effervescent'') at http://www.fda.gov/cder/dsm/DRG/drg00201.htm.
3. The United States Pharmacopeia 28-National Formulary 23,
Supplement 2, The United States Pharmacopeial Convention, Inc.,
Rockville, MD, pp 3520, 2005.
List of Subjects in 21 CFR Part 341
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
341 is amended as follows:
PART 341--COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC
DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE
0
1. The authority citation for 21 CFR part 341 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
0
2. Section 341.3 is amended by adding paragraph (i) to read as follows:
Sec. 341.3 Definitions.
* * * * *
(i) Effervescent dosage form. A dosage form intended to be
dissolved in water before administration. It contains, in addition to
the active ingredient(s), mixtures of acids (citric acid, tartaric
acid) and sodium bicarbonate, which release carbon dioxide when
dissolved in water.
0
3. Section 341.20 is amended by adding paragraph (a) (4) to read as
follows:
Sec. 341.20 Nasal decongestant active ingredients.
* * * * *
(a) * * *
(4) Phenylephrine bitartrate in an effervescent dosage form.
* * * * *
0
4. Section 341.80 is amended by revising the headings in paragraphs
(c)(1)(i) and (c)(1)(ii), and by adding paragraph (d)(1)(iii) to read
as follows:
Sec. 341.80 Labeling of nasal decongestant drug products.
* * * * *
(c) * * *
(1) Oral nasal decongestants--(i) For products containing
phenylephrine hydrochloride, pseudoephedrine hydrochloride,
pseudoephedrine sulfate, or phenylephrine bitartrate identified in
Sec. 341.20 (a)(1) through (a)(4) when labeled for adults. * * *
* * * * *
(ii) For products containing phenylephrine hydrochloride,
pseudoephedrine hydrochloride, pseudoephedrine sulfate, or
phenylephrine bitartrate identified in Sec. 341.20 (a)(1) through
(a)(4) when labeled for children under 12 years of age. * * *
* * * * *
(d) * * *
(1) * * *
(iii) For products containing phenylephrine bitartrate identified
in Sec. 341.20(a)(4). Include information on the number of dosage
units and the quantity of water the dosage units are to be dissolved in
prior to administration as shown in the following table:
------------------------------------------------------------------------
Age\1\ Dose\1\
------------------------------------------------------------------------
Adults and children 12 years 15.6 milligrams every 4 hours not to
of age and over exceed 62.4 milligrams in 24 hours
------------------------------------------------------------------------
Children 6 to under 12 years 7.8 milligrams every 4 hours not to
of age exceed 31.2 milligrams in 24 hours
------------------------------------------------------------------------
Children under 6 years of age Ask a doctor
------------------------------------------------------------------------
\1\Headings are not required to appear in the product's labeling
* * * * *
0
5. Section 341.85 is amended by revising the headings in paragraphs
(b)(2) and (b)(3).
Sec. 341.85 Labeling of permitted combinations of active ingredients.
* * * * *
(b) * * *
(2) For permitted combinations containing an analgesic-antipyretic
active ingredient identified in Sec. 341.40 (a), (c), (f), (g), (m),
(q), and (r) when labeled for relief of hay fever/allergic rhinitis
and/or nasal congestion symptoms.***
* * * * *
(3) For permitted combinations containing an oral analgesic-
antipyretic active ingredient identified in Sec. 341.40 (a), (c), (f),
(g), (m), (q), and (r) when labeled for relief of general cough-cold
symptoms and/or the common cold and for relief of hay fever/allergic
rhinitis and/or nasal congestion symptoms.***
* * * * *
[[Page 43363]]
Dated: July 24, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-12265 Filed 7-31-06; 8:45 am]
BILLING CODE 4160-01-S