[Federal Register Volume 69, Number 147 (Monday, August 2, 2004)]
[Proposed Rules]
[Pages 46119-46122]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-17445]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 310 and 341

[Docket No. 2004N-0289]
RIN 0910-AF34


Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug 
Products for Over-the-Counter Human Use; Proposed Amendment of Final 
Monograph for Over-the-Counter Nasal Decongestant Drug Products

AGENCY:  Food and Drug Administration, HHS.

ACTION:  Proposed rule.

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SUMMARY:  The Food and Drug Administration (FDA) is proposing to amend 
the final monograph 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 remove the 
indication ``for the temporary relief of nasal congestion associated 
with sinusitis'' and to prohibit use of the terms ``sinusitis'' and 
``associated with sinusitis'' elsewhere on the labeling. This proposal 
is part of FDA's ongoing review of OTC drug products.

DATES: Submit written or electronic comments on the document and 
comments on the agency's economic impact determination by November 1, 
2004. See sections V and X of this document for the proposed effective 
and compliance dates of any final rule that may publish based on this 
proposal.

ADDRESSES: You may submit comments, identified by [Docket No. 2004N-
0289 and/or RIN number 0910-AF34], by any of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.
     Agency Web site: http://www.fda.gov/dockets/ecomments. 
Follow the instructions for submitting comments on the agency Web site.
     E-mail: [email protected]. Include [Docket No.2004N-
0289 and/or RIN number 0910-AA01] in the subject line of your e-mail 
message.
     FAX: 301-827-6870.
     Mail/Hand delivery/Courier [For paper, disk, or CD-ROM 
submissions]: Division of Dockets Management, 5630 Fishers Lane, rm. 
1061, Rockville, MD 20852.
    Instructions: All submissions received must include the agency name 
and Docket No. or Regulatory Information Number (RIN) for this 
rulemaking. All comments received will be posted without change to 
http://www.fda.gov/dockets/ecomments, including any personal 
information provided. For detailed instructions on submitting comments 
and additional information on the rulemaking process, see the 
``Comments'' heading of the SUPPLEMENTARY INFORMATION section of this 
document.
    Docket: For access to the docket to read background documents or 
comments received, go to http://www.fda.gov/dockets/ecomments and/or 
the Division of Dockets Management, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Michael T. Benson, 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

A. Advance Notice of Proposed Rulemaking

    In the Federal Register of September 9, 1976 (41 FR 38312), the 
Advisory Review Panel on OTC Cold, Cough, Allergy, Bronchodilator, and 
Antiasthmatic Drug Products (the Panel) recommended the following as 
one of 13 labeling indications for OTC nasal decongestant drug 
products: ``For temporary relief of nasal congestion associated with 
sinusitis.'' (See 41 FR 38312 at 38422.) The Panel recommended 13 
indications for OTC nasal decongestant drug products (41 FR 38312 at 
38403 to 38404). Only one of these indications involved the term 
``sinusitis,'' i.e., ``For temporary relief of nasal congestion 
associated with sinusitis.'' The Panel did not provide any explanation 
for this indication in its general discussion of OTC nasal 
decongestants (41 FR 38312 at 38396 to 38397) or in its Category I 
labeling discussion.

B. Tentative Final Monograph

    In the Federal Register of January 15, 1985 (50 FR 2220), FDA 
concurred with the Panel's recommendation and proposed a similar 
indication in the tentative final monograph for OTC nasal decongestant 
drug products. That indication in proposed Sec.  341.80(b)(1) (50 FR 
2220 at 2238) stated: ``For the temporary relief of nasal congestion 
due to the common cold (cold), hay fever'' (which may be followed by 
any of the following: ``(allergic rhinitis),'' ``or other upper 
respiratory allergies,'' or ``or other upper respiratory allergies 
(allergic rhinitis'') ``or associated with sinusitis.''

C. Final Monograph

    In the Federal Register of August 23, 1994 (59 FR 43386), FDA 
published a final monograph with a similar indication included in Sec.  
341.80(b)(1)(iii). The complete indication for OTC nasal decongestant 
drug products in Sec.  341.80(b)(1) states:
    (Select one of the following: ``For the temporary relief of 
nasal congestion'' or ``Temporarily relieves nasal congestion'') 
(which may be followed by any of the following in paragraphs 
(b)(1)(i), (ii), and (iii) of this section):
    (i) ``due to'' (select one of the following: ``the common cold'' 
or ``a cold'').
    (ii) ``due to'' (select one of the following: ``hay fever,'' 
``hay fever (allergic rhinitis),'' ``hay fever or other upper 
respiratory allergies,'' or ``hay fever or other upper respiratory 
allergies (allergic rhinitis)''); and
    (iii) ``associated with sinusitis.''

II. Sinusitis

A. General Discussion

    Sinusitis is characterized by inflammation of the paranasal 
passages (Ref. 1). Primary care providers and subspecialists often 
recommend antibiotics for the management of acute sinusitisand chronic 
sinusitis because these conditions often have a bacterial etiology 
(Refs. 1 through 4). Other nasal diseases may have symptoms similar to 
those of sinusitis. These include allergic and nonallergic rhinitis, 
the common cold or influenza, Wegener's granulomatosis, acquired and 
congenital immunodeficiency diseases, nasal polyposis, sarcoidosis, 
fungal sinusitis, or neoplasm (Refs. 1 and 3). Further, sinusitis and 
asthma often occur together in the same person. As many as 40 to 70 
percent of people with asthma

[[Page 46120]]

have accompanying sinusitis (Ref. 1). Moreover, complications of acute 
bacterial sinusitis include infections of the orbit (bony cavity that 
contains the eyeball), the central nervous system, or both. These 
complications are rare, but have the potential to result in blindness 
or death (Ref. 2).

B. Recent Developments

    Recent publications (Refs. 1 and 2) indicate that prospective 
studies on the role of nasal decongestants in the treatment of 
sinusitis are lacking, and the data on their use as an adjunct in the 
treatment of sinusitis are limited and controversial. Despite the lack 
of evidence for their use, nasal decongestants are recommended or 
prescribed by health care providers as adjunctive therapy for 
sinusitis. This treatment occurs within a physician-patient 
relationship and should not be construed as evidence that consumers 
should self-diagnose and self-manage sinusitis. In addition, there is 
preclinical evidence that topical nasal decongestants may have a 
negative effect on the resolution of sinusitis, as they may increase 
the degree of sinus inflammation (Ref. 3).
    Sinusitis develops in approximately 31 million Americans each year. 
Acute sinusitis typically follows a viral infection of the upper 
respiratory tract or occurs as a complication of allergic rhinitis. 
Swelling of the nasal mucous membranes may obstruct the sinus ostia 
(openings), resulting in retained secretions, impaction of mucus, 
decreased oxygenation, and changes in pressure within the sinus 
cavities. Retained secretions and impacted mucus may become infected 
and produce increased congestion and inflammation of the sinus mucosa, 
and may lead to the clinical symptoms associated with acute sinusitis, 
such as nasal discharge containing pus, postnasal drip, facial pain and 
headache, and nasal congestion. Treatment is directed towards curing 
the infection and restoring normal sinus openings and drainage. Health 
care providers often recommend nasal decongestants as adjunctive 
therapy for acute sinusitis (Ref. 1).

III. FDA's Concerns

    Due to the current labeling, FDA is concerned that consumers use 
OTC nasal decongestant drug products (both oral and topical) to treat 
symptoms associated with sinusitis, rather than seeking medical 
evaluation and definitive treatment. The delay in medical evaluation 
could also result in a lost opportunity for early diagnosis of another 
serious medical condition in patients who have symptoms similar to 
those of sinusitis. Consumers who have bacterial sinusitis could 
potentially have their condition worsen by delaying treatment with 
appropriate antibiotic medications, possibly resulting in serious 
complications. Consumers who have both sinusitis and accompanying 
asthma could have complications from both diseases if there is a delay 
in appropriate evaluation and treatment of their asthma. Due to the 
data contained in recent publications and the potential medical harms 
described in this section, FDA now considers the indication ``for the 
temporary relief of nasal congestion associated with sinusitis'' 
inappropriate and potentially misleading in the labeled uses for OTC 
nasal decongestant drug products. Consumers could interpret this 
indication to mean that the product can be used for self-treating 
sinusitis. Likewise, use of the term ``sinusitis'' on the product's 
principal display panel could cause the same misunderstanding.

IV. FDA's Proposal

A. What is Included?

    FDA is proposing to remove the partial labeling indication 
``associated with sinusitis'' from the monograph for OTC nasal 
decongestant drug products by removing Sec.  341.80(b)(1)(iii). FDA is 
also including both ``sinusitis'' and ``associated with sinusitis'' as 
nonmonograph conditions in proposed Sec.  310.545(a)(6)(ii)(C).

B. What Is Not Included?

    This proposal does not affect other ``sinus'' claims in the 
monograph. These claims include:
     ``Helps decongest sinus openings and passages'' (Sec.  
341.80(b)(2)(iv)),
     ``Temporarily relieves sinus congestion and pressure'' 
(Sec.  341.80(b)(2)(iv) and (b)(2)(v)), and
     ``Promotes nasal and/or sinus drainage'' (Sec.  
341.80(b)(2)(v)).

V. Analysis of Impacts

    FDA has examined the impacts of this proposed rule under Executive 
Order 12866 and 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 a rule has a significant 
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, which includes an assessment 
of anticipated costs and benefits before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.''
    FDA believes that this proposed rule is consistent with the 
principles set out in Executive Order 12866 and in these two statutes. 
FDA has determined that 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. As discussed later in this 
section, FDA believes that the proposed rule, if finalized, 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 proposed rule, 
because the proposed rule is not expected to result in any 1-year 
expenditure that would exceed $100,000,000 adjusted for inflation. The 
current inflation adjusted statutory threshold is about $110,000,000.
    The purpose of this proposed rule is to remove a labeling claim for 
OTC nasal decongestantdrug products. Removal of this claim should 
reduce possible misuse and improve consumers' self-use of these 
products. FDA does not anticipate that removal of this claim will 
significantly affect OTC sales of these products.
    The proposed rule would require relabeling of some OTC nasal 
decongestant drug products, i.e., those products that currently have a 
claim for sinusitis in their labeling. FDA's drug listing system 
identifies about 1,121 manufacturers and 381 marketers of approximately 
1,960 stockkeeping units (SKUs) (individual products, packages, and 
sizes) of OTC nasal decongestant drug products. These numbers include 
some products marketed under a new drug application (NDA) or 
abbreviated new drug application (ANDA). In addition, there may be a 
few additional marketers and products that are not identified in the 
sources FDA reviewed. FDA is using 2,000 SKUs as an approximate number 
of products in the marketplace that would be affected by this proposed 
rule.

[[Page 46121]]

    FDA has reviewed the labeling of some of these nasal decongestant 
drug products and found that 74 of 100 products did not have a 
sinusitis claim. Extrapolating these numbers to approximately 2,000 
SKUs of these products, the agency estimates that approximately 520 
products (26 percent) would have to be relabeled. FDA estimates (based 
on information provided by OTC drug manufacturers) that the proposed 
rule would impose total one-time compliance costs on industry for 
relabeling of about $3,000 to $4,000 per SKU, for a total cost for 520 
SKUs of $1,560,000 to $2,080,000.
    FDA believes the actual cost could be lower for several reasons. 
First, as FDA explained in the final rule for OTC drug product labeling 
requirements (64 FR 13254 at 13280, March 17, 1999), most of the 
labeling changes will be made by private label small manufacturers that 
tend to use simpler and less expensive labeling. Second, FDA is 
proposing a period of 18 months (24 months for products with annual 
sales less than $25,000) after the date of publication of a final rule 
based on this proposal for manufacturers to implement the new labeling. 
Thus, manufacturers should be able to use up existing labeling stocks 
and to make the labeling changes in the normal course of business. 
Further, manufacturers will not incur any expenses determining how to 
state the product's labeling because the proposed amendment (and any 
final rule based on this proposal) provides that information. Any final 
rule that publishes based on this proposal will not be expected to 
require any new reporting and recordkeeping activities. Therefore, no 
additional professional skills would be needed.
    FDA considered, but rejected several labeling alternatives: (1) A 
shorter or longer implementation period and (2) an exemption from 
coverage for small entities. While FDA believes that consumers would 
benefit from having this proposed labeling in place as soon as 
possible, FDA also acknowledges that a shorter implementation period 
could significantly increasethe compliance costs and these costs could 
be passed through to consumers. A longer time period would 
unnecessarily delay the benefit of new labeling to consumers who self-
medicate with these drug products. FDA rejected an exemption for small 
entities because the new labeling information is also needed by 
consumers who purchase products marketed by those entities. However, a 
longer compliance date (24 months) is being provided for products with 
annual sales less than $25,000.
    OTC nasal decongestant drug products are not the sole products 
produced by manufacturers affected by this rule. FDA believes the 
incremental costs of this proposed rule will be less than 1 percent of 
any manufacturer's total sales. Thus, this economic analysis, together 
with other relevant sections of this document, serves as FDA's initial 
regulatory flexibility analysis, as required under the Regulatory 
Flexibility Act.

VI. Paperwork Reduction Act of 1995

    FDA tentatively concludes that the labeling requirement proposed in 
this document is not subject to review by the Office of Management and 
Budget because it does not constitute a ``collection of information'' 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).
    Rather, the proposed removal of a labeling claim 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)).

VII. 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.

VIII. 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, 
FDA 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.

IX. Request for Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this document. 
Submit one paper copy of electronic comments or three paper copies of 
any mailed comments, except that individuals may submit one paper copy. 
Comments are to be identified with the docket number found in brackets 
in the heading of this document and may be accompanied by a supporting 
memorandum or brief. Received comments may be seen in the Division of 
Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.

X. Proposed Effective and Compliance Dates

    FDA is proposing that any final rule based on this proposal become 
effective 18 months after the date of its publication in the Federal 
Register. FDA is proposing the following compliance dates for nasal 
decongestant drug products marketed under the monograph:
     24 months after the date of publication of a final rule in 
the Federal Register for products with annual sales less than $25,000 
and
     18 months after the date of publication in the Federal 
Register for all other such drug products.

XI. References

    The following references are on display in the Division of Dockets 
Management (see ADDRESSES) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.
    1. Parameters for the Diagnosis and Management of Sinusitis, 
supplement to The Journal of Allergy and Clinical Immunology, 102 (6 
Part 2): S107-S144, December 1998.
    2. American Academy of Pediatrics Subcommittee on Management of 
Sinusitis and Committee on Quality Improvement, ``Clinical Practice 
Guideline: Management of Sinusitis,'' Pediatrics, 108(3): 798-808, 
2001.
    3. ``Report of the Rhinosinusitis Task Force Committee 
Meeting,'' Otolaryngology-Head and Neck Surgery, 117 (3 Part 2): S1-
S68, 1997.
    4. Snow, V., et al., ``Principles of Appropriate Antibiotic Use 
for Acute Sinusitis in Adults,'' Annals of Internal Medicine, 134 
(6): 495-497, 2001.

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, it is 
proposed that 21 CFR parts 310 and 341 be amended as follows:

PART 310--NEW DRUGS

    1. The authority citation for 21 CFR part 310 continues to read as 
follows:


[[Page 46122]]


    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)(ii)(C) to 
read as follows:


Sec.  310.545  Drug products containing certain active ingredients 
offered over-the-counter (OTC) for certain uses.

    (a) * * *
    (6) * * *
    (ii) * * *
    (C) Approved as of [Date 18 months after date of publication of the 
final rule in the Federal Register]; [date 24 months after date of 
publication of the final rule in the Federal Register], for products 
with annual sales less than $25,000. Any ingredient(s) labeled with 
claims or directions for use for sinusitis or for relief of nasal 
congestion associated with sinusitis.
* * * * *

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: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
    4. Section 341.80 is amended by removing paragraph (b)(1)(iii).

    Dated: July 23, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-17445 Filed 7-30-04; 8:45 am]
BILLING CODE 4160-01-S