68 FR 33 pgs. 7919-7921 - Ophthalmic Drug Products for Over-the-Counter Human Use; FinalMonograph; Technical Amendment
Type: RULEVolume: 68Number: 33Pages: 7919 - 7921
Docket number: [Docket No. 03N-0008]
FR document: [FR Doc. 03-3926 Filed 2-18-03; 8:45 am]
Agency: Health and Human Services Department
Sub Agency: Food and Drug Administration
Official PDF Version: PDF Version
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; FinalMonograph; Technical Amendment
AGENCY:
Food and Drug Administration, HHS.
ACTION:
Final rule; technical amendment.
SUMMARY:
The Food and Drug Administration (FDA) isamending the regulation that established conditions under whichover-the-counter (OTC) ophthalmic drug products are generally recognized assafe and effective and not misbranded. This amendment clarifies the activeingredient in OTC eyewash drug products and the labeling of the activeingredient and its purpose. This final rule is part of FDA's ongoingreview 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 labelingrevision after the effective date of March 21, 2003.
Comment Dates : Submit written or electronic comments byApril 21, 2003.
ADDRESSES:
Submit written comments to the DocketsManagement Branch (HFA-305), Food and Drug Administration, 5630Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic commentsto http://www.fda.gov/dockets/ecomments .
FOR FURTHER INFORMATION CONTACT:
Gerald M. Rachanow,Center for Drug Evaluation and Research (HFD-560), Food and DrugAdministration, 5600 Fishers Lane, Rockville, MD 20857,301-827-2307.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of March 4, 1988 (53 FR 7076), FDAissued a final monograph for OTC ophthalmic drug products (part 349 (21 CFRpart 349)). Section 349.20 of that monograph states that eyewashes containwater, tonicity agents to establish isotonicity with tears, agents forestablishing pH and buffering to achieve the same pH as tears, and asuitable preservative agent.
In the Federal Register of March 17, 1999 (64 FR 13254),FDA issued a final rule establishing standardized format and contentrequirements for the labeling of OTC drug products (§ 201.66 (21CFR 201.66)). Section 201.66(c)(2) requires the labeling to state theestablished name of each active ingredient and the quantity in each dosageunit stated in the directions for use. Section 201.66(c)(3) requires thelabeling to state the purpose of each active ingredient, which is thegeneral pharmacological category or the principal intended action of thedrug. When an OTC drug monograph contains a statement of identity, thepharmacological action described in the statement of identity shall also bestated 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 clarificationon how to list the active and inactive ingredients for these products tocomply with § 201.66(c)(2) and (c)(8). The agency hasdetermined that the active ingredient of these eyewash drug products iswater, and that tonicity, hydrogen-ion concentration (pH) and buffering,and preservative agents should be listed as inactive ingredients. Based onthe statement of identity in § 349.78(a), the agency has alsodetermined 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 (21U.S.C. 352(e)(1)(A)(i)) (the act) requires the label of a drug to bear theestablished name of the drug to the exclusion of any other nonproprietaryname (except the applicable systematic chemical name or the chemicalformula). The established name of the drug is defined as
* * *(A) the applicable official name designatedpursuant to section 508 [of the act], or (B) if there is no such name andsuch drug, or such ingredient, is an article recognized in an officialcompendium, then the official title thereof in such compendium, or (C) ifneither clause (A) nor clause (B) of this subparagraph applies, then thecommon 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 anofficial name for any drug if FDA determines "that such action isnecessary or desirable in the interest of usefulness and simplicity"(21 U.S.C. 358(a)). FDA does not, however, routinely designate officialnames for drug products under section 508 of the act (21 CFR 299.4(e)). Inthe absence of designation by FDA of an official name, interested personsmay rely on the current compendial name as the established name(§ 299.4(e)). FDA has not designated an official name forwater. The current compendial name for water is "purifiedwater," which should appear in product labeling.
III. The Technical Amendment
The agency is revising § 349.20 to state: "The activeingredient of the product is purified water. The product also containssuitable tonicity agents to establish isotonicity with tears, suitableagents for establishing pH and buffering to achieve the same pH as tears,and a suitable preservative agent." The agency is also revising thestatement of identity for eyewash drug products in § 349.78(a)to delete "eye lotion" and replace it with "eyeirrigation." The agency does not consider the term "eyelotion" fully informative to consumers in stating the purpose of thewater in the eyewash drug product. Manufacturers should state the purposeof the water as either "eyewash" or "eyeirrigation."
Section 201.66(c)(2) requires the labeling to state the quantity of eachactive ingredient. For products marketed without discrete dosage directions, such as eyewashes, the labeling should state the proportion ofeach active ingredient. For eyewashes, the quantity of water should bestated as the percentage of the total product, which is likely to be 98 to99 percent. It is not necessary to state "in each bottle" oran amount per dosage unit.
To the extent that 5 U.S.C. 553 applies to this action, it is exemptfrom notice and comment because it constitutes a rule of agency procedureunder 5 U.S.C. 553(b)(3)(A). Alternatively, the agency's implementation ofthis action without opportunity for public comment comes within the goodcause exceptions in 5 U.S.C. 553(b)(3)(B) in that obtaining public commentis impracticable, unnecessary, and contrary to public interest. Thislabeling revision represents a minor clarifying change that does not changethe substance of the labeling requirements contained in the finalregulations. In accordance with 21 CFR 10.40(e)(1), FDA is providing anopportunity for comment on whether the regulation should be modified orrevoked.
IV. Analysis of Impacts
FDA has examined the impacts of the final rule under Executive Order12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), and theUnfunded Mandates Reform Act of 1995 (Public Law 104-4). ExecutiveOrder 12866 directs agencies to assess all costs and benefits of availableregulatory alternatives and, when regulation is necessary, to selectregulatory approaches that maximize net benefits (including potentialeconomic, 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 ofsmall entities, an agency must analyze regulatory options that wouldminimize any significant impact of the rule on small entities. Section202(a) of the Unfunded Mandates Reform Act of 1995 requires that agenciesprepare a written statement of anticipated costs and benefits beforeproposing any rule that may result in an expenditure in any one year bystate, local, and tribal governments, in the aggregate, or by the privatesector, of $100 million (adjusted annually for inflation).
The agency concludes that this final rule is consistent with theprinciples set out in Executive Order 12866 and in these two statutes. TheUnfunded Mandates Reform Act of 1995 does not require FDA to prepare astatement of costs and benefits for this final rule, because the final ruleis not expected to result in any 1-year expenditure that would exceed $100million adjusted for inflation. The current inflation adjusted statutorythreshold is about $110 million. No further analysis is required under theRegulatory Flexibility Act because the agency has determined that thisfinal rule will not have a significant effect on a substantial number ofsmall entities.
As discussed previously, FDA is implementing this action to clarify thefinal monograph for OTC ophthalmic drug products. This will facilitatecompliance with the labeling provisions in § 201.66. OTCophthalmic drug products were supposed to be in compliance with thissection by May 16, 2002. The agency believes that while some products mayhave already incorporated the labeling format described in this technicalamendment, other products have not.
The agency believes 25 manufacturers produce approximately 40 eyewashproducts, which are represented by up to 60 stock keeping units (SKUs). Tominimize any impacts on any of these manufacturers not currently incompliance, the agency is providing them with up to 24 months (or the dateof the first major labeling revision of the product after the effectivedate 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 notexceed $3,000. Based on this information, the total one-time costs ofrelabeling would be $180,000 ($3,000 per SKU x 60 SKUs). The average costper manufacturer would be $7,200 ($180,000 / 25 manufacturers). Theseestimates likely overstate the true burden of this rule, as the agencybelieves some manufacturers may already be in compliance and would incur noadditional costs. Also, some manufacturers might be able to make thesechanges during the implementation period as part of routinely scheduledlabel revisions.
The Regulatory Flexibility Act requires the agency to analyze whether arule may have a significant impact on a substantial number of smallentities. According to the Small Business Administration, manufacturers ofOTC ophthalmic drug products, as part of the North American IndustryClassification System (NAICS) code 325412 (pharmaceutical preparations),are small entities if they have fewer than 750 employees. The agency hasreviewed information on the manufacturers of OTC eyewash drug products andbelieves 22 of the 25 manufacturers are small entities. These smallentities have average annual revenues of $10.7 million. The cost of therule per affected small entity would be 0.067 percent ($7,200 / $10.7million) of average annual revenues.
The two smallest of these small entities have reported annual revenuesof approximately $1 million. The agency believes one of thesemanufacturers to have three SKUs. The total cost of the final rule forthis 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 lessthan 1 percent of annual revenues. The agency therefore certifies thatthis final rule will not have a significant impact on a substantial numberof small entities.
V. Paperwork Reduction Act of 1995
The agency concludes that the labeling requirements in this document arenot subject to review by the Office of Management and Budget because theydo not constitute a "collection of information" under thePaperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq. ).Rather, the labeling statements are a "public disclosure ofinformation originally supplied by the Federal Government to the recipientfor the purpose of disclosure to the public" (5 CFR1320.3(c)(2)).
VI. Environmental Impact
The agency has determined under 21 CFR 25.31(a) that this action is of atype that does not individually or cumulatively have a significant effecton the human environment. Therefore, neither an environmental assessmentnor an environmental impact statement is required.
VII. Federalism
FDA has analyzed this final rule in accordance with the principles setforth in Executive Order 13132. FDA has determined that the rule does notcontain policies that have substantial direct effects on the States, on therelationship between the National Government and the States, or on thedistribution of power and responsibilities among the various levels ofgovernment. Accordingly, the agency has concluded that the rule does notcontain policies that have federalism implications as defined in theExecutive order and, consequently, a federalism summary impact statement isnot 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 of any writtencomments, except that individuals may submit one hard copy. Comments areto be identified with the docket number found in brackets in the heading ofthis document and may be accompanied by a supporting memorandum or brief.Received comments may be seen in the Dockets Management Branch between 9a.m. and 4 p.m., Monday through Friday.
List of Subjects in 21 CFR Part 349
Labeling, Opthalmic goods and services, Over-the-counterdrugs.
Therefore, under the Federal Food, Drug, and Cosmetic Act and underauthority delegated to the Commissioner of Food and Drugs, 21 CFR part 349is amended as follows:
PART 349-OPHTHALMIC DRUG PRODUCTS FOR OVER-THE-COUNTERHUMAN USE
1. The authority citation for 21 CFR part 349 continues to read asfollows:
Authority:
21 U.S.C. 321, 351, 352, 353, 355, 360,371.
2. Section 349.20 is revised to read as follows:
§ 349.20 Eyewashes.
The active ingredient of the product is purified water. The productalso contains suitable tonicity agents to establish isotonicity with tears,suitable agents for establishing pH and buffering to achieve the same pH astears, and a suitable preservative agent.
3. Section 349.78 is amended by revising paragraph (a) to read asfollows:
§ 349.78 Labeling of eyewashdrug products.
(a) Statement of identity . The labeling of the productidentifies the product with one or more of the following terms:"eyewash," "eye irrigation," or "eyeirrigating 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