[Federal Register Volume 60, Number 52 (Friday, March 17, 1995)]
[Rules and Regulations]
[Pages 14355-14357]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-6649]



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DEPARTMENT OF AGRICULTURE
9 CFR Part 113

[Docket No. 93-057-2]


Viruses, Serums, Toxins, and Analogous Products; Sampling of 
Biological Products

AGENCY: Animal and Plant Health Inspection Service, USDA.

ACTION: Final rule.

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SUMMARY: We are amending the regulations concerning the number of 
representative samples of product that a firm is required to submit to 
the Animal and Plant Health Inspection Service for testing at the 
National Veterinary Services Laboratories, Ames, Iowa. The amendment is 
applicable to diagnostic test kits and Master Seeds and Cells, and will 
codify provisions which are not currently in the regulations.

EFFECTIVE DATE: April 17, 1995.

FOR FURTHER INFORMATION CONTACT: Dr. Richard E. Pacer, Senior Staff 
Veterinarian, Animal and Plant Health Inspection Service, 
Biotechnology, Biologics, and Environmental Protection, Veterinary 
Biologics, 4700 River Road, Unit 148, Riverdale, MD 20737-1228, (301) 
734-8245.

SUPPLEMENTARY INFORMATION:

Background

    The regulations in 9 CFR Part 113 contain standard requirements for 
evaluating veterinary biological products that are licensed by the 
Animal and Plant Health Inspection Service (APHIS), U.S. Department of 
Agriculture, under the Virus-Serum-Toxin Act of 1913, as amended by the 
Food Security Act of 1985. Licenses are required to show that 
biological products are pure, safe, potent, and efficacious.
    Purity and identify tests are performed by the licensee and the 
National Veterinary Services Laboratories (NVSL) on master seed(s) and 
master cell stock(s) used in the production of veterinary biological 
products. The licensee is also required to perform tests on the 
completed veterinary biological product for purity, safety, and potency 
as prescribed in a filed outline of production or applicable standard 
requirements for the product in accordance with Sec. 113.5. The 
licensee's test results may be confirmed by NVSL personnel using 
representative biological product samples that the manufacturer is 
required to submit to APHIS in accordance with Sec. 113.3.
    Section 113.3 currently provides licensees and permittees with 
criteria for selection and submission of veterinary biological 
products, such as [[Page 14356]] vaccines, bacterins, antiserums, and 
toxoids to NVSL. Section 113.3, however, does not state the number of 
samples of diagnostic test kits and master seeds and cells required by 
NVSL for product evaluation. These amendments specify that a minimum of 
1 sample of a diagnostic test kit, 10 samples of bacterial master 
seeds, 13 samples of viral master seeds, and 36 milliliters of master 
cell stocks will be required for evaluation at NVSL.
    Finally, minor editorial changes are made in Sec. 113.309 to 
reflect organizational changes within APHIS.
    On March 24, 1994, we published in the Federal Register (59 FR 
13896-13897, Docket No. 93-057-1) the proposal to amend Sec. 113.3.
    We solicited comments for a 60-day period ending May 23, 1994. Two 
comments were received by that date. Both comments were from licensed 
manufacturers of veterinary biological products. The commenters were in 
favor of the proposed rule, but suggested certain changes.
    The first commenter felt that the 1 milliliter (ml) sample volume 
for master seeds and cells was too restrictive and suggested that a 
volume of ``1 ml or larger'' be specified along with a minimum total 
volume. Proposed paragraph (c) of Sec. 113.3 specified that ``a minimum 
individual volume of 1 ml shall be submitted.'' The proposed wording 
thus did not restrict the total volume to only 1 ml. In response to the 
commenter, we have amended Sec. 113.3(c)(3) as follows:

    Thirty-six samples of at least 1 ml each or six samples of at 
least 1 ml each, one sample of at least 20 ml, and one sample of at 
least 10 ml of Master Cell Stocks. In the case of Master Cell Stocks 
which are persistently infected with a virus, an additional four 
samples of at least 1 ml each are required. If these persistently 
infected cell stocks are intended for use in more than one species, 
an additional two samples of at least 1 ml are required for each 
additional species.

    The second commenter requested clarification regarding diagnostic 
test kits when the final product packages contains more than one 
microtiter test plate. Several diagnostic test kits are designed to use 
96-well microtiter test plates or 12- or 16-well microtiter test 
strips. The proposed rule (Sec. 113.3(b)(7)) specified the submission 
of ``two samples of diagnostic test kits'' as a general rule and ``a 
minimum of one diagnostic kit'' in the preamble of the rule. As the 
commenter pointed out, multiple test plates or test strips may be 
packaged together with other test reagents in a single product. In the 
case of a product with multiple microtiter test plates or test strips, 
APHIS would not need to test all of the test plates or test strips for 
proper evaluation of the product. In response to the commenter, we have 
amended Sec. 113.3(b)(7) and Sec. 113.3(e)(1) to require the submission 
of a specified number of test plates or test strips along with all 
other test reagents as prescribed in a filed Outline of Production when 
a diagostic test kit contains multiple microtiter test plates or test 
strips.

Executive Order 12866 and Regulatory Flexibility Act

    This rule has been reviewed under Executive Order 12866. The rule 
has been determined to be not significant for purposes of Executive 
Order 12866, and, therefore, has not been reviewed by the Office of 
Management and Budget.
    There are currently no criteria in the regulations which specify 
the number of samples needed by NVSL to evaluate diagnostic test kits 
and Master Seeds and Cells. Almost all of the 114 licensed veterinary 
biologics companies currently submit samples of Master Seeds and Cells 
to NVSL for testing. In addition, at least 25 of these companies 
produce veterinary diagnostic test kits and submit samples of them to 
NVSL for testing. Many of these companies would be considered small 
entities. This rule will benefit these entities by clarifying the 
current requirements.
    This rule will reduce the licensees' time and expense in submitting 
samples to the NVSL by specifying the number of samples required, by 
increasing the uniformity of sample submissions, and by allowing for 
more efficient handling of samples by licensees and APHIS personnel. In 
addition, this amendment could increase revenues for manufacturers of 
veterinary diagnostic test kits by allowing them to return unrequested 
samples to inventory for sale.
    Under these circumstances, the Administrator of the Animal and 
Plant Health Inspection Service has determined that this action will 
not have a significant economic impact on a substantial number of small 
entities.

Executive Order 12372

    This program/activity is listed in the Catalog of Federal Domestic 
Assistance under No. 10.025 and is subject to Executive Order 12372, 
which requires intergovernmental consultation with State and local 
officials. (See 7 CFR part 3015, subpart V.)

Executive Order 12778

    This rule has been reviewed under Executive Order 12778, Civil 
Justice Reform: This rule: (1) Preempts all State and local laws and 
regulations that are in conflict with this rule; (2) has no retroactive 
effect; and (3) does not require administrative proceedings before 
parties may file suit in court challenging this rule.

Paperwork Reduction Act

    This rule contains no new information collection or recordkeeping 
requirements under the Paperwork Reduction Act of 1980 (44 U.S.C. 3501 
et seq.).

List of Subjects in 9 CFR Part 113

    Animal biologics Exports, Imports, Reporting and recordkeeping 
requirements.
    Accordingly, 9 CFR part 113 is amended as follows:

PART 113--STANDARD REQUIREMENTS

    1. The authority citation for part 113 continues to read as 
follows:

    Authority: 21 U.S.C. 151-159; 7 CFR 2.17, 2.51, and 371.2(d).

    2. In Sec. 113.3, paragraphs (b)(7), (b)(8) and (b)(9) are revised, 
paragraph (b)(10) is removed, paragraph (c) is revised, and new 
paragraphs (d) and (e) are added to read as follows:


Sec. 113.3  Sampling of biological products.

* * * * *
    (b) * * *
    (7) Diagnostic test kits: Two samples of diagnostic test kits. The 
licensee or permittee will hold one of these selected samples at the 
storage temperature recommended on the label while awaiting a request 
by the animal and Plant Health Inspection Service to submit the 
additional sample. If submission is not requested by the Animal and 
Plant Health Inspection Service, the additional sample may be returned 
to the serial inventory after the serial is released. In the case of 
diagnostic test kits in which final packaging consists of multiple 
microtiter test plates or strips, the licensee or permittee may submit 
a specified number of test plates or strips along with all other test 
reagents as prescribed in a filed Outline of Production and retain a 
similar amount as a second sample for submission upon request. When the 
initial sample is not representative of final packaging by the licensee 
of permittee, e.g., does not consist of all the microtiter test plates 
or strips, the second sample is not eligible to be returned to serial 
inventory after the serial is released.
    (8) Autogenous biologics: Ten samples shall be selected from each 
serial of autogenous biologic that exceeds 50 containers. No samples, 
other than those [[Page 14357]] required by paragraph (e) of this 
section, are required for a serial of autogenous biologic with 50 or 
fewer containers.
    (9) Miscellaneous: The number of samples from products not in the 
categories provided for in paragraphs (b)(1) through (b)(8) of this 
section shall be prescribed in the filed Outline of Production for the 
product.
    (c) Prelicensing and Outline of Production changes: Samples needed 
to support a license application or a change in the Outline of 
Production for a licensed product shall be submitted only upon request 
from the animal and Plant Health Inspection Service. Except for 
miscellaneous products specified in paragraph (b)(9) of this section, 
the number of such samples shall be at least one and one-half times the 
number prescribed for such product in paragraph (b) of this section. 
Samples of Master Seeds and Master Cell Stocks with a minimum 
individual volume of 1 ml shall be submitted as follows:
    (1) Ten samples of Bacterial Master Seeds.
    (2) Thirteen samples of viral Master Seeds or nonviral Master Seeds 
requiring cell culture propagation. For Master Seeds isolated or passed 
in a cell line different from the species of intended use, an 
additional 2 samples are required for each additional species. For 
Master Seeds grown in cell culture and intended for use in more than 
one species, an additional 2 samples are required for each additional 
species.
    (3) Thirty-six samples of at least 1 ml each or six samples of at 
least 1 ml each, one sample of at least 20 ml, and one sample of at 
least 10 ml of Master Cell Stocks. In the case of Master Cell Stocks 
which are persistently infected with a virus, an additional four 
samples of at least 1 ml each are required. If these persistently 
infected cell stocks are intended for use in more than one species, an 
additional two samples of at least 1 ml each are required for each 
additional species.
    (4) Four samples of the Master Cell Stock + n (highest passage) 
cells.
    (d) Sterile diluent: A sample of Sterile Diluent shall accompany 
each sample of product, other than Marek's Disease Vaccine, if such 
diluent is required to rehydrate or dilute the product before use. The 
volume of diluent shall be an appropriate amount to rehydrate or dilute 
the product. Samples of Sterile Diluent prepared for use with Marek's 
Disease Vaccine shall be submitted upon request from the Animal and 
Plant Health Inspection Service.
    (e) Reserve samples shall be selected from each serial and 
subserial of biological product. Such samples shall be selected at 
random from final containers of completed product by an employee of the 
Department, of the licensee, or of the permittee, as designated by the 
administrator. Each sample shall:
    (1) Consist of 5 single-dose packages, 2 multiple-dose packages, or 
2 diagnostic test kits, except that, in the case of diagnostic test 
kits in which final packaging consists of multiple microtiter test 
plates or strips, a sample may consist of a specified number of test 
plates or strips along with all other test reagents as prescribed in a 
filed Outline of Production;
    (2) Be adequate in quantity for appropriate examination and 
testing;
    (3) Be truly representative and in final containers;
    (4) Be held in a special compartment set aside by the licensee or 
permittee for holding these samples under refrigeration at the storage 
temperature recommended on the labels for 6 months after the expiration 
date stated on the labels. The samples that are stored in this manner 
shall be delivered to the Animal and Plant Health Inspection Service 
upon request.

(Approved by the Office of Management and Budget under control 
number 0579-0013)


Sec. 113.309  [Amended]

    3. In Sec. 113.309, paragraph (c)(4), the words ``Veterinary 
Services'' are removed and the words ``Animal and Plant Health 
Inspection Service'' are added in their place.

    Done in Washington, DC, this 13th day of March 1995.
Terry L. Medley,
Acting Administrator, Animal and Plant Health Inspection Service.
[FR Doc. 95-6649 Filed 3-16-95; 8:45 am]
Billing Code 3410-34-M