[Federal Register Volume 68, Number 33 (Wednesday, February 19, 2003)]
[Rules and Regulations]
[Pages 7919-7921]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-3926]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 349

[Docket No. 03N-0008]
RIN 0910-AA01


Ophthalmic Drug Products for Over-the-Counter Human Use; Final 
Monograph; Technical Amendment

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule; technical amendment.

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SUMMARY: The Food and Drug Administration (FDA) is amending the 
regulation that established conditions under which over-the-counter 
(OTC) ophthalmic drug products are generally recognized as safe and 
effective and not misbranded. This amendment clarifies the active 
ingredient in OTC eyewash drug products and the labeling of the active 
ingredient and its purpose. This final rule is part of FDA's ongoing 
review of OTC drug products.

DATES: Effective Date: This rule is effective March 21, 2003.
    Compliance Dates: The compliance dates are either February 21, 
2005, or the date of the first major labeling revision after the 
effective date of March 21, 2003.
    Comment Dates: Submit written or electronic comments by April 21, 
2003.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments.

FOR FURTHER INFORMATION CONTACT: Gerald M. Rachanow, Center for Drug 
Evaluation and Research (HFD-560), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-2307.

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of March 4, 1988 (53 FR 7076), FDA issued a 
final monograph for OTC ophthalmic drug products (part 349 (21 CFR part 
349)). Section 349.20 of that monograph states that eyewashes contain 
water, tonicity agents to establish isotonicity with tears, agents for 
establishing pH and buffering to achieve the same pH as tears, and a 
suitable preservative agent.
    In the Federal Register of March 17, 1999 (64 FR 13254), FDA issued 
a final rule establishing standardized format and content requirements 
for the labeling of OTC drug products (Sec.  201.66 (21 CFR 201.66)). 
Section 201.66(c)(2) requires the labeling to state the established 
name of each active ingredient and the quantity in each dosage unit 
stated in the directions for use. Section 201.66(c)(3) requires the 
labeling to state the purpose of each active ingredient, which is the 
general pharmacological category or the principal intended action of 
the drug. When an OTC drug monograph contains a statement of identity, 
the pharmacological action described in the statement of identity shall 
also be stated as the purpose of the active ingredient. Section 
201.66(c)(8) requires a listing of the established name of each 
inactive ingredient.

II. Clarification

    Manufacturers of OTC eyewash drug products have requested 
clarification on how to list the active and inactive ingredients for 
these products to comply with Sec.  201.66(c)(2) and (c)(8). The agency 
has determined that the active ingredient of these eyewash drug 
products is water, and that tonicity, hydrogen-ion concentration (pH) 
and buffering, and preservative agents should be listed as inactive 
ingredients. Based on the statement of identity in Sec.  349.78(a), the 
agency has also determined that the purpose of the water may be stated 
as either ``eyewash'' or ``eye irrigation.''
    Section 502(e)(1)(A)(i) of the Federal Food, Drug, and Cosmetic Act 
(21 U.S.C. 352(e)(1)(A)(i)) (the act) requires the label of a drug to 
bear the established name of the drug to the exclusion of any other 
nonproprietary name (except the applicable systematic chemical name or 
the chemical formula). The established name of the drug is defined as
    * * *(A) the applicable official name designated pursuant to 
section 508 [of the act], or (B) if there is no such name and such 
drug, or such ingredient, is an article recognized in an official 
compendium, then the official title thereof in such compendium, or 
(C) if neither clause (A) nor clause (B) of this subparagraph 
applies, then the common or usual name, if any, of such drug or of 
such ingredient * * *.
(21 U.S.C. 352(e)(3))
    Section 508 of the act (21 U.S.C. 358) authorizes FDA to designate 
an official name for any drug if FDA determines ``that such action is 
necessary or desirable in the interest of usefulness and simplicity'' 
(21 U.S.C. 358(a)). FDA does not, however, routinely designate official 
names for drug products under section 508 of the act (21 CFR 299.4(e)). 
In the absence of designation by FDA of an official name, interested 
persons may rely on the current compendial name as the established name 
(Sec.  299.4(e)). FDA has not designated an official name for water. 
The current compendial name for water is ``purified water,'' which 
should appear in product labeling.

III. The Technical Amendment

    The agency is revising Sec.  349.20 to state: ``The active 
ingredient of the product is purified water. The product also contains 
suitable tonicity agents to establish isotonicity with tears, suitable 
agents for establishing pH and buffering to achieve the same pH as 
tears, and a suitable preservative agent.'' The agency is also revising 
the statement of identity for eyewash drug products in Sec.  349.78(a) 
to delete ``eye lotion'' and replace it with ``eye irrigation.'' The 
agency does not consider the term ``eye lotion'' fully informative to 
consumers in stating the purpose of the water in the eyewash drug 
product. Manufacturers should state the purpose of the water as either 
``eyewash'' or ``eye irrigation.''
    Section 201.66(c)(2) requires the labeling to state the quantity of 
each active ingredient. For products marketed without discrete dosage

[[Page 7920]]

directions, such as eyewashes, the labeling should state the proportion 
of each active ingredient. For eyewashes, the quantity of water should 
be stated as the percentage of the total product, which is likely to be 
98 to 99 percent. It is not necessary to state ``in each bottle'' or an 
amount per dosage unit.
    To the extent that 5 U.S.C. 553 applies to this action, it is 
exempt from notice and comment because it constitutes a rule of agency 
procedure under 5 U.S.C. 553(b)(3)(A). Alternatively, the agency's 
implementation of this action without opportunity for public comment 
comes within the good cause exceptions in 5 U.S.C. 553(b)(3)(B) in that 
obtaining public comment is impracticable, unnecessary, and contrary to 
public interest. This labeling revision represents a minor clarifying 
change that does not change the substance of the labeling requirements 
contained in the final regulations. In accordance with 21 CFR 
10.40(e)(1), FDA is providing an opportunity for comment on whether the 
regulation should be modified or revoked.

IV. Analysis of Impacts

    FDA has examined the impacts of the 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 a rule has a significant economic impact on a 
substantial number of small entities, an agency must analyze regulatory 
options that would minimize any significant impact of the rule on small 
entities. Section 202(a) of the Unfunded Mandates Reform Act of 1995 
requires that agencies prepare a written statement of anticipated costs 
and benefits before proposing any rule that may result in an 
expenditure in any one year by state, local, and tribal governments, in 
the aggregate, or by the private sector, of $100 million (adjusted 
annually for inflation).
    The agency concludes that this final rule is consistent with the 
principles set out in Executive Order 12866 and in these two statutes. 
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 inflation 
adjusted statutory threshold is about $110 million. No further analysis 
is required under the Regulatory Flexibility Act because the agency has 
determined that this final rule will not have a significant effect on a 
substantial number of small entities.
    As discussed previously, FDA is implementing this action to clarify 
the final monograph for OTC ophthalmic drug products. This will 
facilitate compliance with the labeling provisions in Sec.  201.66. OTC 
ophthalmic drug products were supposed to be in compliance with this 
section by May 16, 2002. The agency believes that while some products 
may have already incorporated the labeling format described in this 
technical amendment, other products have not.
    The agency believes 25 manufacturers produce approximately 40 
eyewash products, which are represented by up to 60 stock keeping units 
(SKUs). To minimize any impacts on any of these manufacturers not 
currently in compliance, the agency is providing them with up to 24 
months (or the date of the first major labeling revision of the product 
after the effective date of this final rule, whichever occurs first) to 
relabel their products. The agency believes the cost of a label change 
to a particular SKU will not exceed $3,000. Based on this information, 
the total one-time costs of relabeling would be $180,000 ($3,000 per 
SKU x 60 SKUs). The average cost per manufacturer would be $7,200 
($180,000 / 25 manufacturers). These estimates likely overstate the 
true burden of this rule, as the agency believes some manufacturers may 
already be in compliance and would incur no additional costs. Also, 
some manufacturers might be able to make these changes during the 
implementation period as part of routinely scheduled label revisions.
    The Regulatory Flexibility Act requires the agency to analyze 
whether a rule may have a significant impact on a substantial number of 
small entities. According to the Small Business Administration, 
manufacturers of OTC ophthalmic drug products, as part of the North 
American Industry Classification System (NAICS) code 325412 
(pharmaceutical preparations), are small entities if they have fewer 
than 750 employees. The agency has reviewed information on the 
manufacturers of OTC eyewash drug products and believes 22 of the 25 
manufacturers are small entities. These small entities have average 
annual revenues of $10.7 million. The cost of the rule per affected 
small entity would be 0.067 percent ($7,200 / $10.7 million) of average 
annual revenues.
    The two smallest of these small entities have reported annual 
revenues of approximately $1 million. The agency believes one of these 
manufacturers to have three SKUs. The total cost of the final rule for 
this particular small entity would be 0.9 percent (3 SKUs x $3,000 per 
SKU / $1 million). Thus, the impact on any of the small entities would 
be less than 1 percent of annual revenues. The agency therefore 
certifies that this final rule will not have a significant impact on a 
substantial number of small entities.

V. Paperwork Reduction Act of 1995

    The agency 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 labeling statements are 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

    The agency 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, the agency has concluded 
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. Opportunity for Comments

    Interested persons may submit to the Dockets Management Branch (see 
ADDRESSES) written or electronic comments regarding this document. 
Submit a single copy of electronic comments to http://www.fda.gov/dockets/ecomments or three hard copies

[[Page 7921]]

of any written comments, except that individuals may submit one hard 
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 
Dockets Management Branch between 9 a.m. and 4 p.m., Monday through 
Friday.

List of Subjects in 21 CFR Part 349

    Labeling, Opthalmic goods and services, 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 part 
349 is amended as follows:

PART 349--OPHTHALMIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE

    1. The authority citation for 21 CFR part 349 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
    2. Section 349.20 is revised to read as follows:


Sec.  349.20   Eyewashes.

    The active ingredient of the product is purified water. The product 
also contains suitable tonicity agents to establish isotonicity with 
tears, suitable agents for establishing pH and buffering to achieve the 
same pH as tears, and a suitable preservative agent.
    3. Section 349.78 is amended by revising paragraph (a) to read as 
follows:


Sec.  349.78  Labeling of eyewash drug products.

    (a) Statement of identity. The labeling of the product identifies 
the product with one or more of the following terms: ``eyewash,'' ``eye 
irrigation,'' or ``eye irrigating solution.''
* * * * *

    Dated: January 31, 2003.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 03-3926 Filed 2-18-03; 8:45 am]
BILLING CODE 4160-01-S