[Federal Register Volume 70, Number 195 (Tuesday, October 11, 2005)]
[Rules and Regulations]
[Pages 58974-58977]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-20304]


=======================================================================
-----------------------------------------------------------------------

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; Amendment of Final Monograph 
for Over-the-Counter Nasal Decongestant Drug Products

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is amending 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 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 final 
rule is part of FDA's ongoing review of OTC drug products.

DATES: Effective Date: This regulation is effective April 11, 2007.
    Compliance Dates: The compliance date for products with annual 
sales less than $25,000 is October 11, 2007. The compliance date for 
all other products is April 11, 2007.

FOR FURTHER INFORMATION CONTACT: Michael T. Benson, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Silver Spring, MD 20993, 301-796-2090.

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of August 2, 2004 (69 FR 46119), FDA 
published a proposed rule to amend the FM for OTC nasal decongestant 
drug products 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. 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). 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

[[Page 58975]]

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 
consumers 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 of this document, 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. FDA received three comments on its proposed 
rule.

II. FDA's Response to the Comments

    (Comment 1) One comment disagreed with the proposed rule and 
contended that FDA should be compelled to provide valid scientific data 
prior to taking the action noted in the proposed rule. The comment 
stated that:
     Consumers are not likely to misunderstand symptom 
treatment to also mean disease treatment.
     Consumers would know that they have sinusitis only after 
intervention by a physician.
     Consumers with recurrent sinusitis may be able to 
recognize the signs and be able to begin to treat the nasal congestion 
with an OTC nasal decongestant as they seek medical intervention.
     Consumers may be unaware that they have sinusitis and 
treat the associated nasal congestion with a nasal decongestant drug 
product, thereby allowing the sinusitis to progress in some cases.
     Because OTC nasal decongestant drug product labeling warns 
consumers to stop taking the medication and consult a doctor if their 
symptoms do not improve within 7 days or if the symptoms are 
accompanied by fever, consumers who follow that labeling would 
discontinue use of the product if they experienced fever (a symptom 
associated with a bacterial infection in sinusitis) or if the condition 
lasted more than 7 days.
     If the proposed rule is finalized, there will be no OTC 
labeled product that can be used for sinusitis, leaving consumers only 
with the option of medical intervention to begin treatment of their 
symptoms. This option will lead to a greater demand for antibiotics, 
including for episodes where not necessarily needed, which will lead to 
worsening of the public health due to antibiotic resistance.
     FDA has not produced data to show that [alpha]-adrenergic 
decongestants are not appropriate for relief of nasal congestion 
associated with sinusitis.
     Current consumer-oriented medical information continues to 
note that nasal decongestants are recommended by physicians for nasal 
congestion associated with sinusitis. As examples, the comment cited 
the following information:
    1. The American Academy of Otolaryngology-Head and Neck Surgery 
(AAOHNS) notes that oral and topical nasal decongestants may be used to 
alleviate nasal congestion associated with sinusitis.
    2. The National Institute of Allergy and Infectious Diseases 
(NIAID) (National Institutes of Health, U.S. Department of Health and 
Human Services) notes that physicians may recommend decongestants to 
reduce congestion.
    3. The American Academy of Allergy, Asthma & Immunology (AAAAI) 
notes that in addition to prescribing an antibiotic to control the 
bacterial infection, physicians may prescribe a decongestant to reduce 
blockage.
     The current labeling for these products does not delay 
consumers from seeking appropriate treatment for sinusitis.
    (Comments 2 and 3) A second comment from the AAAAI agreed with 
FDA's proposal to delete reference to sinusitis in the labeling of OTC 
nasal decongestant drug products and stated that the proposal is 
reasonable, appropriate, and a step in the right direction. A third 
comment, from a consumer, fully agreed with removal of ``sinusitis'' 
from the product labeling. The person who submitted the comment 
considered himself to be an average consumer of OTC drug products who 
contracts sinusitis at least twice a year and stated that:
     The main argument in support of the proposal is evidence 
that these drugs are lacking when they are recommended or prescribed 
for adjunctive therapy for sinusitis.
     Evidence suggests that OTC drugs may have negative effects 
on the treatment of sinusitis and can worsen the condition.
     Such labeling is almost a form of false advertising, that 
the indications are misleading, and that consumers should not be led to 
believe such labeling is acceptable.
     If consumers use OTC drugs to self-treat sinusitis and the 
condition is not properly treated, the condition could worsen 
dramatically, with consumers having the risk of becoming clinically 
worse and/or developing further complications.
     FDA is correct in its removal of the ``sinusitis'' 
language to ensure that the probability of consumers using OTC drugs 
for self-treatment of sinusitis will be reduced.
    FDA disagrees with the comment opposing the proposed rule. FDA 
initially affirmed the recommendation by the Advisory Review Panel on 
OTC Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug 
Products in its advance notice of proposed rulemaking (48 FR 38312, 
September 9, 1976) to include the ``sinusitis'' term in OTC nasal 
decongestant drug product labeling. However, due to the data in recent 
publications and the potential harms described in this document, FDA no 
longer considers sinusitis an appropriate OTC indication and believes 
that the current labeling is potentially misleading to consumers. 
Appropriate care of sinusitis requires the attention of a health care 
practitioner. FDA is concerned that consumers may interpret current 
product labeling as implying that a nasal decongestant can treat 
sinusitis and will delay consulting a physician for treatment.
    The comment that disagreed with the proposed rule referred to 
current consumer-oriented information. The comment stated that this 
information continues to note that nasal decongestants are recommended 
by physicians for nasal congestion associated with sinusitis. For 
example,
     NIAID notes that physicians may recommend decongestants to 
reduce congestion.
     AAAAI notes that physicians may prescribe a medication 
such as a decongestant to reduce blockage in addition to prescribing an 
antibiotic to control the bacterial infection.
These references clearly indicate that use of decongestants and/or 
adjunct therapy is at the discretion of a physician. It should also be 
noted that AAAAI submitted a comment agreeing with FDA's proposal.

[[Page 58976]]

    The comment that disagreed with the proposed rule implies that a 
consumer who uses an OTC nasal decongestant drug product will not delay 
seeking medical attention for sinusitis because the OTC nasal 
decongestant drug product labeling warns consumers to consult a doctor 
if their symptoms do not improve within 7 days or are accompanied by 
fever. However, the presence of fever in consumers with sinusitis is 
variable (Ref. 2), and decongestant products may be combined with an 
analgesic that can mask these symptoms. No data were submitted to 
support the contention that consumers are not likely to misunderstand 
symptom treatment to also mean disease treatment. Neither were data 
submitted to support the contention that current labeling does not 
delay consumers from seeking appropriate treatment for sinusitis. FDA 
agrees with comments that state that diagnosis and definitive treatment 
of sinusitis requires intervention by a physician, and that consumers 
who are unaware that they have sinusitis may allow the condition to 
progress. Although FDA is not aware of data supporting the use of 
[alpha]-adrenergic decongestants in sinusitis, FDA recognizes that 
physicians may advocate their use. This advocacy does not, however, 
make sinusitis an OTC indication. FDA concludes that the term 
``sinusitis'' should be removed from OTC nasal decongestant drug 
product labeling.

III. FDA's Final Conclusions

    FDA is finalizing its proposal by removing Sec.  341.80(b)(1)(iii) 
(21 CFR 341.80(b)(1)(iii)) from the FM for OTC nasal decongestant drug 
products. FDA is also including ``sinusitis'' and ``associated with 
sinusitis'' as nonmonograph conditions in new Sec.  
310.545(a)(6)(ii)(C) (21 CFR 310.545(a)(6)(ii)(C)).
    In addition, FDA is entering technical changes by substituting 
``nasal congestion'' for ``sinusitis'' in the paragraph headings of 
Sec. Sec.  341.85(b)(2) and (b)(3) (21 CFR 341.85(b)(2) and (b)(3)), 
and by removing the term ``and/or (b)(1)(iii)'' from Sec.  
341.85(b)(2)(ii).
    Twenty-four months after the date of publication in the Federal 
Register, for products with sales less than $25,000, and 18 months 
after the date of publication in the Federal Register, for all other 
products, no OTC drug product that is subject to this final rule and 
that contains a nonmonograph condition may be initially introduced or 
initially delivered for introduction into interstate commerce unless it 
is the subject of a new drug application (NDA) or abbreviated new drug 
application (ANDA). Further, any OTC drug product subject to this final 
rule that is repackaged or relabeled after the compliance dates of the 
final rule must be in compliance with the FM regardless of the date the 
product was initially introduced or initially delivered for 
introduction into interstate commerce. Manufacturers are encouraged to 
comply voluntarily as soon as possible.

IV. Analysis of Impacts

    FDA has examined the impacts of this final 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 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 final rule is consistent with the principles 
set out in Executive Order 12866 and in these two statutes. FDA has 
determined that the 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 of the 
document, FDA concludes that the 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 remove a labeling claim for 
OTC nasal decongestant drug 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 final rule requires 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 an NDA or 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 final 
rule.
    FDA randomly 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, FDA estimates that approximately 520 
products (26 percent) would have to be relabeled. FDA estimates (based 
on information provided by OTC drug manufacturers) that the final 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 
allowing a period of 18 months (24 months for products with annual 
sales less than $25,000) after publication of a final rule 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 final rule provides that information. The final rule does 
not require any new reporting and recordkeeping activities. Therefore, 
no additional professional skills would be needed.

[[Page 58977]]

    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 new labeling in place as soon as possible, FDA 
also acknowledges that a shorter implementation period could 
significantly increase the 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 rejects 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 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 final 
regulatory flexibility analysis, as required under the Regulatory 
Flexibility Act.

V. Paperwork Reduction Act of 1995

    FDA concludes that the labeling requirement 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 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)).

VI. 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.

VII. 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, FDA concludes that the rule 
does not contain policies that have federalism implications as defined 
in the Executive order, and consequently, a federalism summary impact 
statement is not required.

VIII. References

    The following references are on display in the Division of Dockets 
Management, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852, 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.

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.

0
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

0
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.

0
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 April 11, 2007; October 11, 2007, 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

0
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.
0
4. Section 341.80 is amended by removing paragraph (b)(1)(iii),
0
5. Section 341.85 is amended by revising the headings in paragraphs 
(b)(2) and (b)(3) and by revising paragraph (b)(2)(ii) to read as 
follows:


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.
* * * * *
    (ii) The indication(s) for the cough-cold ingredient(s) consists of 
the labeling for antihistamines in Sec.  341.72(b)(1) or (b)(2) and/or 
nasal decongestants in Sec.  341.80(b)(1)(ii), as appropriate, and the 
labeling for any other cough-cold combination. This labeling may follow 
a separate bullet(s) or may be combined with the indication in 
paragraph (b)(2)(i) of this section.
    (b)(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.
* * * * *

    Dated: September 26, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-20304 Filed 10-7-05; 8:45 am]
BILLING CODE 4160-01-S