Federal Register / Vol. 68, No. 106 / Tuesday, June 3, 2003 / Rules and Regulations
`
`32981
`
`■ 2. Section 201.323 is amended by
`revising the first sentence of the
`introductory text of paragraph (c); by
`removing from paragraph (c)(3) the word
`‘‘January’’ and adding in its place the
`word ‘‘July’’; by redesignating
`paragraphs (d) and (e) as paragraphs (e)
`and (f), respectively; and by adding new
`paragraph (d) to read as follows:
`§ 201.323 Aluminum in large and small
`volume parenterals used in total parenteral
`nutrition.
`*
`*
`*
`*
`*
`(c) Except as provided in paragraph
`(d) of this section, the maximum level
`of aluminum present at expiry must be
`stated on the immediate container label
`of all small volume parenteral (SVP)
`drug products and pharmacy bulk
`packages (PBPs) used in the preparation
`of TPN solutions.* * *
`(d) If the maximum level of aluminum
`is 25 µg/L or less, instead of stating the
`exact amount of aluminum as required
`in paragraph (c) of this section, the
`immediate container label may state:
`‘‘Contains no more than 25 µg/L of
`aluminum.’’ If the SVP or PBP is a
`lyophilized powder, the immediate
`container label may state: ‘‘When
`reconstituted in accordance with the
`package insert instructions, the
`concentration of aluminum will be no
`more than 25 µg/L’’.
`*
`*
`*
`*
`Dated: May 22, 2003.
`Jeffrey Shuren,
`Assistant Commissioner for Policy.
`[FR Doc. 03–13752 Filed 6–2–03; 8:45 am]
`BILLING CODE 4160–01–S
`
`*
`
`DEPARTMENT OF HEALTH AND
`HUMAN SERVICES
`Food and Drug Administration
`
`21 CFR Part 349
`[Docket No. 03N–0193]
`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.
`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 updates
`
`the monograph to incorporate a United
`States Pharmacopeia (USP) name
`change for one active ingredient
`included in the monograph. This final
`rule is part of FDA’s ongoing review of
`OTC drug products.
`DATES: This final rule is effective July 3,
`2003. Submit written or electronic
`comments by August 4, 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:
`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
`In the Federal Register of March 4,
`1988 (53 FR 7076), FDA issued a final
`monograph for OTC ophthalmic drug
`products in part 349 (21 CFR part 349).
`Section 349.12 of that monograph
`included the active ingredient
`hydroxypropyl methylcellulose. In
`2000, the USP proposed (for inclusion
`in the Third Supplement to USP 24) a
`name change for this ingredient based
`on a name adopted by the United States
`Adopted Names Council (Ref. 1). The
`new name for hydroxypropyl
`methylcellulose is hypromellose. This
`name change became official on March
`1, 2001, and was subsequently included
`in the USP with an effective date of
`September 1, 2002 (Ref. 2).
`II. Naming Process
`The Federal Food, Drug, and Cosmetic
`Act (the act) in section 502(e)(1)(A)(i)
`(21 U.S.C. 352(e)(1)(A)(i)) 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.’’ FDA does not,
`however, routinely designate official
`names for drug products under section
`508 of the act (§ 299.4(e) (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 (§ 299.4(e)).
`III. The Technical Amendment
`FDA has not designated an official
`name for the active ingredient
`hydroxypropyl methylcellulose. Thus,
`its established name is the current
`compendial name. The USP has now
`changed the compendial name for
`hydroxypropyl methylcellulose to
`hypromellose. To be consistent with the
`change in this official compendial
`name, the agency is changing this name
`in § 349.12 in the ingredient listing. As
`noted previously, this USP name change
`became official on March 1, 2001, with
`a USP effective date of September 1,
`2002.
`Because section 502(e)(1) and (e)(3) of
`the act requires the established name of
`a drug to be used, any ophthalmic drug
`product initially introduced or initially
`delivered for introduction into interstate
`commerce after September 1, 2002,
`would need to bear the new established
`name ‘‘hypromellose.’’ However, the
`agency is aware that many
`manufacturers of OTC ophthalmic drug
`products have not yet implemented this
`name change in their product labeling.
`Therefore, elsewhere in this issue of the
`Federal Register, as a matter of its
`enforcement discretion, the agency is
`issuing guidance stating its intent to
`provide manufacturers of affected OTC
`ophthalmic drug products until
`September 1, 2003 (1 extra year from the
`USP effective date), to implement this
`labeling change. Accordingly, on or after
`September 1, 2003, any OTC ophthalmic
`drug product initially introduced or
`initially delivered for introduction into
`interstate commerce that contains the
`ingredient hypromellose (formerly
`known as hydroxypropyl
`methylcellulose) must bear labeling that
`contains the new name for this
`ingredient.
`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
`
`VerDate Jan<31>2003 14:14 Jun 02, 2003 Jkt 200001 PO 00000 Frm 00027 Fmt 4700 Sfmt 4700 E:\FR\FM\03JNR1.
`
`APOTEX EX1060
`
`Page 1
`
`

`
`32982
`
`Federal Register / Vol. 68, No. 106 / Tuesday, June 3, 2003 / Rules and Regulations
`
`represents a minor clarifying change
`that does not change the substance of
`the labeling requirements contained in
`the final regulations. As discussed
`previously in this document,
`manufacturers must relabel their
`products as a result of the USP name
`change to remain in compliance with
`the act. This amendment updates the
`name of one active ingredient in the
`final monograph for OTC ophthalmic
`drug products to reflect this official
`name change that has already been
`implemented by the USP. 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
`and the Regulatory Flexibility Act (5
`U.S.C. 601–612), and the Unfunded
`Mandates Reform Act of 1995 (UMRA)
`(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 UMRA 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. FDA has determined
`that the 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.
`The UMRA 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.
`The purpose of this final rule is to
`update the final monograph for OTC
`ophthalmic drug products to
`
`incorporate a USP name change for one
`active ingredient included in the
`monograph. As discussed in section II of
`this document, section 502(e)(1) and
`(e)(3) of the act requires that the
`established name of a drug be used.
`Under § 299.4(e), because FDA does not
`routinely designate official names under
`section 508 of the act, the established
`name under section 502(e) of the act
`ordinarily is the compendial name of
`the drug. Therefore, because FDA has
`not designated an official name under
`section 508 of the act, manufacturers
`must relabel their products as a result of
`the USP name change to remain in
`compliance with the act. Updating the
`name of the active ingredient in the
`ophthalmic monograph to reflect its
`current established name will eliminate
`possible confusion by the public.
`Because manufacturers must relabel
`their products as a result of the USP
`name change to remain in compliance
`with the act, this rule does not impose
`any additional costs on industry.
`Consequently, the agency certifies that
`this final rule will not have a significant
`economic impact on a substantial
`number of small entities. Therefore, no
`further analysis is required.
`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. 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 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 Dockets
`Management Branch between 9 a.m. and
`4 p.m., Monday through Friday.
`IX. References
`
`The following references have been
`placed on display in the Dockets
`Management Branch (see ADDRESSES)
`and may be seen by interested persons
`between 9 a.m. and 4 p.m., Monday
`through Friday.
`1. ‘‘Pharmacopeial Forum,’’ The United
`States Pharmacopeial Convention, Inc.,
`Rockville, MD, pp. 702–705, May and June
`2000.
`2. ‘‘Third Supplement,’’ United States
`Pharmacopeia 24, National Formulary 19,
`The United States Pharmacopeial
`Convention, Inc., Rockville, MD, pp. 3041–
`3042, January 2, 2001.
`List of Subjects in 21 CFR Part 349
`
`Labeling, Ophthalmic 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 349.12 is amended by
`revising paragraph (a)(3) to read as
`follows:
`§ 349.12 Ophthalmic demulcents.
`*
`*
`*
`*
`*
`(a) * * *
`(3) Hypromellose, 0.2 to 2.5 percent.
`*
`*
`*
`*
`
`*
`
`VerDate Jan<31>2003 14:14 Jun 02, 2003 Jkt 200001 PO 00000 Frm 00028 Fmt 4700 Sfmt 4700 E:\FR\FM\03JNR1.SGM 03JNR1
`
`Page 2
`
`

`
`Federal Register / Vol. 68, No. 106 / Tuesday, June 3, 2003 / Rules and Regulations
`
`32983
`
`Dated: May 15, 2003.
`Jeffrey Shuren,
`Assistant Commissioner for Policy.
`[FR Doc. 03–13827 Filed 6–2–03; 8:45 am]
`BILLING CODE 4160–01–S
`
`DEPARTMENT OF HEALTH AND
`HUMAN SERVICES
`Food and Drug Administration
`
`21 CFR Part 878
`[Docket No. 02N–0288]
`Medical Devices; Designation of
`Special Control for Eight Surgical
`Suture Devices
`AGENCY: Food and Drug Administration,
`HHS.
`ACTION: Final rule.
`SUMMARY: The Food and Drug
`Administration (FDA) is issuing a final
`rule to amend the classification
`regulations for eight surgical suture
`devices previously reclassified into
`class II to specify a special control for
`those devices. The special control is an
`FDA guidance document entitled ‘‘Class
`II Special Controls Guidance Document:
`Surgical Sutures; Guidance for Industry
`and FDA’’ that identifies performance,
`testing, and labeling recommendations
`for the devices. Elsewhere in this issue
`of the Federal Register, FDA is
`announcing the availability of the
`guidance document that will serve as
`the special control. FDA is taking these
`actions on its own initiative because it
`believes they are necessary to provide
`reasonable assurance of the safety and
`effectiveness of surgical suture devices.
`These actions are being taken under the
`Federal Food, Drug, and Cosmetic Act
`(the act).
`DATES: This rule is effective July 3,
`2003.
`FOR FURTHER INFORMATION CONTACT:
`Anthony D. Watson, Center for Devices
`and Radiological Health (HFZ–410),
`Food and Drug Administration, 9200
`Corporate Blvd., Rockville, MD 20850,
`301–594–3090, ext. 164.
`SUPPLEMENTARY INFORMATION:
`I. Background
`The act (21 U.S.C. 301 et seq.), as
`amended by the Medical Device
`Amendments of 1976 (the 1976
`amendments) (Public Law 94–295), the
`Safe Medical Devices Act of 1990
`(SMDA) (Public Law 101–629), the Food
`and Drug Administration Modernization
`Act (FDAMA) (Public Law 105–115),
`and the Medical Device User Fee and
`Modernization Act (MDUFMA) (Public
`
`Law 107–250) established a
`comprehensive system for the regulation
`of medical devices intended for human
`use. Section 513 of the act (21 U.S.C.
`360c) established three categories
`(classes) of devices, depending on the
`regulatory controls needed to provide
`reasonable assurance of their safety and
`effectiveness. The three categories of
`devices are class I (general controls),
`class II (special controls), and class III
`(premarket approval).
`Under the 1976 amendments, class II
`devices were defined as those devices
`for which there is insufficient
`information to show that general
`controls themselves will assure safety
`and effectiveness, but for which there is
`sufficient information to establish
`performance standards to provide such
`assurance.
`SMDA broadened the definition of
`class II devices to mean those devices
`for which the general controls by
`themselves are insufficient to provide
`reasonable assurance of safety and
`effectiveness, but for which there is
`sufficient information to establish
`special controls to provide such
`assurance, including performance
`standards, postmarket surveillance,
`patient registries, development and
`dissemination of guidelines,
`recommendations, and any other
`appropriate actions the agency deems
`necessary (section 513(a)(1)(B) of the
`act).
`The 1976 amendments also broadened
`the definition of ‘‘device’’ in 201(h) of
`the act (21 U.S.C. 321(h)) to include
`certain articles that were once regulated
`as drugs. Under the 1976 amendments,
`Congress classified into class III all
`transitional devices, i.e., those devices
`previously regulated as new drugs,
`including surgical sutures.
`II. Regulatory History of the Devices
`In the Federal Register of December
`16, 1977 (42 FR 63472), FDA published
`a notice that identified sutures as class
`III devices under the transitional
`provisions of the act. Section 520(l)(2) of
`the act (21 U.S.C. 360j(l)(2)) provides
`that the manufacturer or importer of a
`device classified in class III under the
`transitional provisions may file a
`petition for reclassification of the device
`into class I or class II. Procedures for
`filing and review of classification
`petitions are set forth in § 860.136 (21
`CFR 860.136).
`In accordance with section 520(l)(2) of
`the act and § 860.136, and after
`consulting with members of the General
`and Plastic Surgery Devices Panel, FDA
`reclassified surgical suture devices from
`class III to class II as follows:
`
`1. Absorbable poly(glycolide/L-
`lactide) surgical suture (21 CFR
`878.4493), reclassification order (letter)
`dated September 14, 1989;
`2. Stainless steel suture (21 CFR
`878.4495), reclassification order (letter)
`dated July 30, 1986;
`3. Absorbable surgical gut suture (21
`CFR 878.4830), reclassification order
`(letter) dated September 19, 1988;
`4. Nonabsorbable poly(ethylene
`terephthalate) surgical suture (21 CFR
`878.5000), reclassification order (letter)
`dated July 5, 1990;
`5. Nonabsorbable polypropylene
`surgical suture (21 CFR 878.5010),
`reclassification order (letter) dated July
`5, 1990;
`6. Nonabsorbable polyamide surgical
`suture (21 CFR 878.5020),
`reclassification order (letter) dated
`February 15, 1990;
`7. Natural nonabsorbable silk surgical
`suture (21 CFR 878.5030),
`reclassification order (letter) dated
`November 9, 1990; and
`8. Nonabsorbable expanded
`polytetrafluoroethylene surgical suture
`(21 CFR 878.5035), reclassification order
`(letter) dated September 9, 1999.
`In the Federal Register of December
`19, 2002 (67 FR 77678), FDA published
`a proposed rule to designate a special
`control for eight surgical suture devices
`already classified into class II. FDA
`proposed that surgical suture devices
`would remain in class II, but would be
`subject to a special control. The
`proposed rule identified the special
`control as an FDA guidance document
`entitled ‘‘Class II Special Controls
`Guidance Document: Surgical Sutures;
`Guidance for Industry and FDA.’’ In the
`same edition of the Federal Register,
`FDA announced the availability of the
`draft guidance that, when final, was
`intended to serve as a special control
`(67 FR 77797). FDA invited interested
`persons to comment on the proposed
`rule and on the proposed special control
`guidance document by March 19, 2003.
`III. FDA’s Conclusion
`FDA received no comments on the
`proposed rule or on the guidance
`document proposed as the special
`control. Therefore, under the SMDA
`authority, FDA is amending the
`classification regulations for eight
`surgical suture devices previously
`reclassified into class II, to designate a
`special control for those devices. The
`special control capable of providing
`reasonable assurance of safety and
`effectiveness for these devices is a
`guidance document entitled ‘‘Class II
`Special Controls Guidance Document:
`Surgical Sutures; Guidance for Industry
`and FDA’’ that identifies performance,
`
`VerDate Jan<31>2003 14:14 Jun 02, 2003 Jkt 200001 PO 00000 Frm 00029 Fmt 4700 Sfmt 4700 E:\FR\FM\03JNR1.SGM 03JNR1
`
`Page 3