56916 Federal Register / Vol. 75, No. 180 / Friday, September 17, 2010 / Proposed Rules

by land to Mexico or Canada, shall be accordance with § 91.14(a), or at a port ∑ Federal eRulemaking Portal: Go to exported through said ports or through or inspection facility designated by the (http://www.regulations.gov/ ports designated in special cases under Administrator in a special case under fdmspublic/component/ paragraph (b) of this section. § 91.14(b). main?main=DocketDetail&d=APHIS- (b) In special cases, other ports may * * * * * 2009-0028) to submit or view comments be designated as ports of embarkation by Done in Washington, DC, this 13th day and to view supporting and related the Administrator, with the concurrence of September 2010. materials available electronically. of the Commissioner of the Bureau of ∑ Postal Mail/Commercial Delivery: Customs and Border Protection, when Kevin Shea, Please send one copy of your comment the exporter can show to the satisfaction Acting Administrator, Animal and Plant to Docket No. APHIS-2009-0028, of the Administrator that the animals to Health Inspection . Regulatory Analysis and Development, be exported would suffer undue [FR Doc. 2010–23245 Filed 9–16–10: 8:45 am] PPD, APHIS, Station 3A-03.8, 4700 hardship if they are required to be BILLING CODE 3410–34–S River Road Unit 118, Riverdale, MD moved to a port listed as a designated 20737-1238. Please state that your port of embarkation in accordance with comment refers to Docket No. APHIS- paragraph (a) of this section. Ports shall DEPARTMENT OF 2009-0028. be designated in special cases as ports Reading Room: You may read any Animal and Plant Health Inspection of embarkation only if the inspection comments that we receive on Service facilities are approved as meeting the Regulations.gov (see the link above) or requirements of paragraph (c) of this in our reading room. The reading room 9 CFR Parts 101 and 114 section. is located in room 1141 of the USDA * * * * * [Docket No. APHIS-2009-0028] South Building, 14th Street and Independence Avenue, SW., (d) Approval and denial or revocation RIN 0579-AD06 of approval. Approval of each export Washington, DC. Normal reading room inspection facility for designation under Viruses, Serums, Toxins, and hours are 8 a.m. to 4:30 p.m., Monday paragraph (a) of this section, and in Analogous Products; Expiration Date through Friday, except holidays. To be special cases under paragraph (b) of this Required for Serials and Subserials sure someone is there to help you, section, shall be obtained from the and Determination of Expiration Date please call (202) 690-2817 before Administrator. Approval of an export of Product coming. inspection facility under paragraph (a) Other Information: Additional or (b) will be denied or revoked for AGENCY: Animal and Plant Health information about APHIS and its failure to meet the standards in Inspection Service, USDA. programs is available on the Internet at paragraph (c) of this section. Designated ACTION: Proposed rule; withdrawal and (http://www.aphis.usda.gov). ports of embarkation and export reproposal. FOR FURTHER INFORMATION CONTACT: Dr. facilities shall be reevaluated annually, Albert P. Morgan, Chief of Operational by means of an APHIS site inspection, SUMMARY: We are proposing to amend Support, Center for Veterinary for continued compliance with the the Virus-Serum-Toxin Act regulations Biologics, Licensing and Policy standards contained in paragraph (c) of concerning expiration dating to clarify Development, VS, APHIS, 4700 River this section. If the port or facility fails that the expiration date of a serial or Road Unit 148, Riverdale, MD 20737- to pass the annual inspection, its subserial of a veterinary biologic should 1231; (301) 734-8245. be computed from the date of the designation will be revoked, and it will SUPPLEMENTARY INFORMATION: be removed from the list of designated initiation of the first potency test. We ports and facilities. A written notice of also propose to require the expiration Background any proposed denial or revocation shall dating period (stability) of a product to The Virus-Serum-Toxin Act be given to the operator of the facility, be confirmed by conducting a real-time regulations in 9 CFR part 114, and he will be given an opportunity to stability study with a stability- ‘‘ Requirements for Biological present his views thereon. Such notice indicating assay; require stability Products’’ (referred to below as the shall list in detail the deficiencies monitoring of products after licensing; regulations), include requirements concerned. After remedying the and specify a single standard for applicable to computing expiration deficiencies, an operator may request determining the expiration date for dates and determining expiration dating another inspection. Approval of a port veterinary biologics in place of the periods (stability) for veterinary of embarkation in connection with the current standard that specifies different biologics. Currently, § 114.12 of the designation of an export inspection procedures for products contingent regulations requires each serial or facility in special cases shall be limited upon whether they consist of viable or subserial of veterinary biological to the special case for which the nonviable organisms. These product prepared in a licensed designation was made. amendments would update and clarify establishment to be given an expiration the regulations concerning expiration * * * * * date, and § 114.13 provides that the dating and establish a single uniform ■ expiration date for each product shall be 3. In § 91.15, paragraph (a) is revised standard for determining the stability of to read as follows: computed from the date of the initiation veterinary biological products. This of the potency test. § 91.15 Inspection of animals for export. proposed rule replaces a previously The computed expiration date of a (a) All animals offered for exportation published proposed rule, which we are serial or subserial of biological product to any foreign country, except by land withdrawing as part of this document. is inextricably linked to the stability of to Mexico or Canada, shall be inspected DATES: We will consider all comments such product. The expiration date of a within 24 hours of embarkation by an that we receive on or before November veterinary biologic designates the end of APHIS veterinarian at an export 16, 2010. the period during which such product, inspection facility at a port listed as a ADDRESSES: You may submit comments when properly stored and handled, can designated port of embarkation in by either of the following methods: be expected with reasonable certainty to

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be efficacious. The most precise for review and filing; the stability data Determination of the Expiration Dating determination of the stability of a approved for filing date to be specified Period of a Product veterinary biologic occurs when the in the filed Outline of Production; and We are proposing to change the title potency of such product is measured at a plan for monitoring the stability of the of § 114.13 from ‘‘Expiration date the end of its predicted shelf life product and the suitability of its determination’’ to ‘‘Determination of the (expiration date). Typically, however, proposed dating period. expiration dating period of a product.’’ We solicited comments on our products are licensed and serials or This change would clarify the fact that proposal for 60 days ending on June 27, subserials are released for marketing the requirements in that section pertain 2005. We received six comments by that before the first production serials reach to determining the stability of a product date. The comments were from three the end of their predicted shelf life. rather than the expiration date of a licensed manufacturers, two national Thus, prior to licensure, licensees and serial or subserial of such product. The permittees must submit preliminary trade associations representing manufacturers of animal health proposed revision of this section would: stability data that provides a level of ∑ Prescribe a single, uniform standard products, and a professional association. confidence that the product will remain for determining the stability of efficacious throughout the dating period All of the commenters agreed with the need to establish a uniform standard for veterinary biologics in place of the shown on its labeling. Typically, such current standards, which prescribe data is obtained by subjecting the determining expiration dating; however, most expressed concern that the different procedures for products product to extreme temperatures for a consisting of viable and nonviable specified time period and measuring the proposed rule lacked detail, and suggested that such detail be added and organisms; relative strength of each fraction by ∑ Remove the wording ‘‘computed conducting a potency test. Products that the rule reproposed. In response to these comments, we from the date of the initiation of the pass the potency test are licensed with potency test’’ and providing that the the provision that the dating period have provided specifics that we believe address the perceived ambiguity in the expiration dating period of a product must be confirmed by real-time stability would be based on the testing of testing at the end of the predicted shelf proposed rule. Therefore, we are withdrawing the April 22, 2005, production serials beginning on the day life. Currently, the requirement of filling into final containers or the date prescribed under § 114.13 of the proposed rule referenced above and replacing it with the proposed changes final formulation of the product if such regulations for confirming stability is date is specified in the filed Outline of contingent upon whether a product described in this document. The proposed requirements for determining Production; consists of viable or nonviable ∑ Require testing of serials or organisms. For products consisting of expiration dating that would apply to each licensee and permittee that subserials using a stability-indicating viable organisms, each serial must be assay on multiple occasions throughout tested for potency at release and at the prepares and distributes veterinary biologics are described below. the predicted dating period in place of approximate expiration date until a the current requirement, which only statistically valid stability record has Definitions requires potency testing at the beginning been established; for nonviable The regulations in 9 CFR part 101 and end of the dating period in order to biological products, each serial contain the definitions of terms used in confirm stability; presented in support of licensure the regulations concerning veterinary ∑ Require the stability data to be (prelicensing serials) must be tested for biologics. The proposed changes to part submitted to APHIS for review and potency at release and at or after the 114 of the regulations would make it filing and the approved for filing date to dating requested. Products with necessary for us to add a definition in be specified in section VI of the filed satisfactory potency tests at the § 101.5 for a term used in the proposed Outline of Production; and beginning and end of dating are regulations: Stability-indicating assay. ∑ Require the periodic testing of considered to be efficacious throughout We would define stability-indicating serials or subserials to monitor the the requested dating period. Current assay as a validated quantitative stability and suitability of the approved science, however, considers stability analytical procedure (in vitro or live dating period. estimates based on potency tests animal test) that can detect changes over APHIS is proposing these conducted at the beginning and end of time in the pertinent properties of a amendments because it has been shown dating (a two-point profile) to be veterinary biologic. that the potency of most veterinary inaccurate and imprecise. biologics degrade in a nonlinear fashion, To address this situation, on April 28, Expiration Date Required for a Serial which may cause potency to degrade 2005, we published in the Federal We are proposing to change the title more quickly than previously estimated. Register (70 FR 21985-21987, Docket of § 114.12 from ‘‘Expiration date Testing on only two occasions would be 1 No. 04-064-1) a proposed rule to amend required’’ to ‘‘Expiration date required reasonable only if potency loss has a the regulations concerning expiration for a serial.’’ In addition, we propose to strictly linear pattern, and this is dating to require veterinary biologics amend this section by adding the usually not the case. Thus, when licensees and permittees to confirm the wording ‘‘computed from the date of the confirming the dating period, APHIS is proposed expiration dating period of initiation of the first potency test.’’ proposing to require the stability of a products by potency testing serials on These changes are intended to clarify product to be evaluated as a function of multiple occasions throughout the the fact that the requirements in this time by requiring serials to be tested on proposed dating period. The proposed section pertain to serials or subserials of multiple occasions with a stability- rule also would have required stability product, and that APHIS interprets the indicating assay. data to be submitted to the Animal and ‘‘date of the initiation of the potency The changes and test procedures Plant Health Inspection Service (APHIS) test’’ to mean the on-test date of the first prescribed in this proposal would potency test conducted on a serial or update and standardize expiration date 1 To view the proposed rule and the comments we received, go to (http://www.regulations.gov/ subserial. This interpretation is determination for veterinary biologics in fdmspublic/component/ consistent with the APHIS policy in that §§ 114.12 and 114.13 by establishing a main?main=DocketDetail&d=APHIS-2005-0041). regard. single, uniform standard for all products

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based on testing and monitoring with a entities subject to the regulations, as the occupy the field. This includes, but is stability-indicating assay. current testing protocols would not not limited to, the regulation of labeling. change; we are simply clarifying those Under the Act, Congress clearly Executive Order 12866 and Regulatory existing protocols. All veterinary intended that there be national Flexibility Act biologics manufacturers are currently uniformity in the regulation of these This proposed rule has been required to confirm the expiration products. There are no administrative determined to be significant for the dating of the products that they produce proceedings which must be exhausted purposes of Executive Order 12866 and, and to submit the data to APHIS for prior to a judicial challenge to the therefore, has been reviewed by the review and filing. In addition, the regulations under this rule. Office of Management and Budget. proposed requirements to test serials of This proposed rule would amend the product on multiple occasions when Paperwork Reduction Act Virus-Serum-Toxin Act regulations in confirming expiration dating, and to This proposed rule contains no new §§ 114.12 and 114.13 concerning monitor stability post-licensing are not information collection or recordkeeping expiration dates and the determination expected to have a significant economic requirements under the Paperwork of the stability of veterinary biologics to: impact because most veterinary Reduction Act of 1995 (44 U.S.C. 3501- Change the title of the sections; clarify biologics manufacturers routinely test 3520). that the ‘‘date of the initiation of the and monitor the stability of products potency test’’ is the on-test date of the throughout their dating period. List of Subjects first potency test conducted on a serial Under the changes to the regulations 9 CFR Part 101 or subserial; require veterinary biologics described in this proposed rule, licensees and permittees to evaluate the veterinary biologics with a 2-year dating Animal biologics. stability of veterinary biologics as a period would require 7 test occasions, 9 CFR Part 114 function of time by testing serials for for a total of 21 tests of 3 serials. To potency on multiple occasions with a confirm expiration dating under current Animal biologics, Reporting and stability-indicating assay throughout regulations, many licensees may be recordkeeping requirements. and after their proposed dating period; required to test 10 serials twice, a total ■ Accordingly, we propose to amend 9 require the stability data approved for of 20 tests. This is about the same CFR parts 101 and 114 as follows: filing date to be specified in the filed number of tests. The most recent data Outline of Production; and require compiled by APHIS show that over one PART 101—DEFINITIONS monitoring of the stability of the 3-year period, 101 veterinary biologics ■ 1. The authority citation for part 101 product and the suitability of its dating manufacturers submitted 105 stability continues to read as follows: period. In addition, the proposed studies to the Center for Veterinary changes to the regulations are consistent Biologics, an average per manufacturer Authority: 21 U.S.C. 151-159; 7 CFR 2.22, with the recommendations of the of 1 every 3 years. The proposed 2.80, and 371.4. collaborative initiative by regulatory amendment to the regulations would ■ 2. Section 101.5 is amended by adding authorities and industry associations not necessitate an increase in the new paragraph (s) to read as follows: known as International Cooperation on number of stability studies required to § 101.5 Testing terminology. Harmonization of Technical be performed, or an increase in Requirements for the Registration of associated testing costs, as these * * * * * Veterinary Medicinal Products (VICH). proposed changes will primarily apply (s) Stability-indicating assay. A VICH is concerned with harmonization to newly licensed products. stability-indicating assay is a validated of technical requirements for the Under these circumstances, the quantitative analytical procedure that registration of veterinary medicinal Administrator of the Animal and Plant can detect changes over time in the products among three regions: The Health Inspection Service has pertinent properties of the product. European Union, Japan, and the United determined that this action would not States. The proposed stability testing have a significant economic impact on PART 114—PRODUCTION guidelines are consistent with those a substantial number of small entities. REQUIREMENTS FOR BIOLOGICAL adopted by VICH as an international PRODUCTS standard for the generation and Executive Order 12372 ■ submission of stability data for This program/activity is listed in the 3. The authority citation for part 114 veterinary medicinal products. The category of Federal Domestic Assistance continues to read as follows: overall benefit of these proposed under No. 10.025 and is subject to Authority: 21 U.S.C. 151-159; 7 CFR 2.22, amendments would be to reduce the Executive Order 12372, which requires 2.80, and 371.4. differences in technical requirements for intergovernmental consultation with ■ 4. Section 114.12 is revised to read as veterinary biologics among regulatory State and local officials. (See 7 CFR part follows: agencies in different countries. 3015, subpart V.) This proposed rule would affect all § 114.12 Expiration date required for a licensed manufacturers of veterinary Executive Order 12988 serial. biologics. Currently, there are This proposed rule has been reviewed Unless otherwise provided for in a approximately 125 veterinary biologics under Executive Order 12988, Civil Standard Requirement or filed Outline manufacturers, including permittees. Justice Reform. It is not intended to of Production, each serial or subserial of According to the standards of the Small have retroactive effect. This rule would biological product prepared in a Administration, most not preempt any State or local laws, licensed establishment shall be given an veterinary biologics establishments are regulations, or policies where they are expiration date computed from the date small entities. Relative to the baseline of necessary to address local disease of the initiation of the first potency test. the existing regulations in §§ 114.12 and conditions or eradication programs. A licensed biological product shall be 114.13, we do not believe that the However, where safety, efficacy, purity, considered worthless under the Virus- changes we are proposing would result and potency of biological products are Serum-Toxin Act after the expiration in new or additional effects on small concerned, it is the Agency’s intent to date appearing on the label.

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■ 5. Section 114.13 is revised to read as (c) In the case of a newly licensed DEPARTMENT OF HOMELAND follows: product, and licensed products whose SECURITY stability studies were completed prior to § 114.13 Determination of the expiration Coast Guard dating period of a product. [Effective date of final rule], a real-time stability study conducted with a An expiration dating period stability-indicating assay in accordance 33 CFR Part 167 determined by the stability of each of its with paragraphs (a) or (b) of this section fractions shall be assigned to each [Docket No. USCG–2010–0785] shall be completed in support of product. Stability shall be determined changes to one of the stability criteria or Port Access Route Study: The with a stability-indicating assay that can Approaches to San Francisco detect changes over time in the for major changes to the potency test. pertinent properties of the product. (d) In the case of a licensed product AGENCY: Coast Guard, DHS. Stability criteria include the with an unconfirmed expiration dating ACTION: Notice of public meetings; specifications for potency at release, period that is tested in animals with a request for comments. potency throughout the dating period, test that is not a stability-indicating and the length of the dating period. assay, the following shall apply: SUMMARY: The Coast Guard announces a When tested at any time during the public meeting to receive comments on (1) Testing involving the use of a non- the study entitled ‘‘Port Access Route dating period, the potency of the stability-indicating assay specified in product shall not be less than the Study: Off San Francisco’’ that was the filed Outline of Production to minimum specified in the filed Outline published in the Federal Register on confirm the expiration dating period for of Production. Prior to licensure, the Thursday, December 10, 2009. As stated licensee shall propose an expiration such product shall be completed by in that document, the Coast Guard is dating period for the product based on [Date 42 months after effective date of conducting a Port Access Route Study preliminary data available about the the final rule], or (PARS) to evaluate the continued stability of each of its fractions. If the (2) Subsequent to [Date 42 months applicability of and the potential need preliminary stability data are after effective date of the final rule], for modifications to the current vessel acceptable, the product may be licensed such testing to confirm expiration routing in the approaches to San with the provision that the proposed dating shall be completed with a Francisco. expiration dating period must be stability-indicating assay. Products not DATES: A Public meeting will be held on confirmed by conducting a real-time meeting the requirement to confirm the Wednesday, October 20, 2010 from 6:30 stability study with a stability- expiration dating with a stability- p.m. to 8:30 p.m. to provide an indicating assay as follows: indicating assay shall be withheld from opportunity for oral comments. Written (a) In the case of a newly licensed the market. comments and related material may also product with acceptable preliminary be submitted to Coast Guard personnel (e) At the completion of the real-time stability data and the real-time stability specified at the meetings. stability study to confirm or change study is not conducted in animals, at ADDRESSES: The October 20, 2010 public least three production serials of the expiration dating, the data shall be submitted to Animal and Plant Health meeting will be held at the Executive product shall be selected and tested Inn and Suites at 1755 Embarcadero, Inspection Service for approval for filing during the proposed dating period. Each Oakland, California. Visitor parking is and the approved for filing date shall be serial shall be tested beginning on the available in the lots outside the hotel. specified in section VI of the filed day of filling into final containers or the FOR FURTHER INFORMATION CONTACT: Outline of Production at the next If date of final formulation specified in the you have questions concerning the revision. filed Outline of Production, and at the meeting or the study, please call or e- following intervals: mail LTJG Lucas Mancini, Coast Guard; (1) Every 3 months during the first (f) For products licensed subsequent telephone 510–437–3801, e-mail year of storage, to [Effective date of the final rule], the [email protected]. If you have (2) Every 6 months during the second licensee or permittee shall submit a plan questions on viewing the docket call year of storage, and to monitor the stability of the product Ms. Renee V. Wright, Program Manager, (3) Annually thereafter throughout the and the suitability of its dating period Docket Operations, telephone 202–366– proposed dating period. that includes regularly testing serials for 9826. (b) In the case of a newly licensed potency with a stability-indicating assay SUPPLEMENTARY INFORMATION: product with acceptable preliminary stability data and the real-time stability during and at the end of dating. Background and Purpose rd study is conducted in animals, at least Done in Washington, DC, this 3 day We published a notice of study in the three production serials shall be tested of September 2010. Federal Register on December 10, 2009 as follows: John Ferrell, (74 FR 65543), entitled ‘‘Port Access (1) One test per serial shall be Route Study: Off San Francisco’’ in conducted beginning on the day of Deputy Under Secretary for Marketing and Regulatory Programs. which we did not state a plan to hold filling into final containers or the date a public meeting. We have decided to of final formulation specified in the [FR Doc. 2010–23186 Filed 9–16–10: 10:57 am] hold a meeting in order to give the filed Outline of Production. BILLING CODE 3410–34–S public and waterway users a chance to (2) One test per serial shall be comment in person. conducted at thebe end of the proposed In the notice of PARS, we discussed dating period. our intent to help reduce the risk of (3) One test per serial shall be marine casualties and increase the conducted between the initial and final efficiency of vessel traffic in the study test, but at a different interval for each region. Our goal is to assess whether the serial. current vessel routing system is effective

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