[Federal Register: October 6, 2003 (Volume 68, Number 193)]
[Rules and Regulations]               
[Page 57607-57608]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06oc03-1]                         






Rules and Regulations
                                                Federal Register
________________________________________________________________________

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[[Page 57607]]



DEPARTMENT OF AGRICULTURE

Animal and Plant Health Inspection Service

9 CFR Part 113

[Docket No. 01-067-2 ]

 
Viruses, Serums, Toxins, and Analogous Products; Determination of 
Moisture Content in Desiccated Biological Products

AGENCY: Animal and Plant Health Inspection Service, USDA.

ACTION: Final rule.

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SUMMARY: We are amending the Virus-Serum-Toxin Act regulations for the 
determination of moisture content in desiccated biological products to 
require that such determinations be made using a gravimetric method 
that expresses moisture content as the percentage of weight a product 
loses during a drying cycle, and to require that the maximum percentage 
of moisture permitted for a satisfactory test must be specified in a 
filed Outline of Production. The gravimetric method has been adopted as 
an international standard by scientific experts and regulatory 
authorities in the United States, Canada, Japan, and the European 
Union. In addition, we are amending the regulations pertaining to 
general requirements for live bacterial vaccines and general 
requirements for live virus vaccines to specify the gravimetric method 
when testing for moisture content. These actions will update the 
regulations by providing a uniform method of determining moisture 
content in desiccated products and ensure the stability of that product 
during its dating period.

EFFECTIVE DATE: November 5, 2003.

FOR FURTHER INFORMATION CONTACT: Dr. Albert P. Morgan, Chief of 
Operational Support, Licensing and Policy Development, Center for 
Veterinary Biologics, VS, APHIS, 4700 River Road Unit 148, Riverdale, 
MD 20737-1231; (301) 734-8245.

SUPPLEMENTARY INFORMATION:

Background

    The Virus-Serum-Toxin Act regulations in 9 CFR part 113 (referred 
to below as the regulations) prescribe standard requirements for the 
preparation and testing of veterinary biological products. Standard 
requirements consist of test methods, procedures, and criteria that 
define the standards for purity, safety, potency, and efficacy for a 
given type of veterinary biologic product. When a standard procedure 
for testing veterinary biological products is validated and approved by 
the Animal and Plant Health Inspection Service (APHIS) for general use, 
it is proposed for codification in the regulations. Section 113.29 of 
the regulations sets forth the requirement for determination of 
moisture content in desiccated biological products.
    On August 5, 2002, we published in the Federal Register (67 FR 
50606-50608, Docket No. 01-067-1) a proposal to amend the regulations 
for determination of moisture content in desiccated biological products 
to specify that such determinations be made using a gravimetric method, 
and to require that the maximum percentage of moisture permitted for a 
satisfactory test must be specified in a filed Outline of Production. 
The proposed rule was intended to update the regulations by providing a 
uniform method of determining moisture content in desiccated products 
and ensure the stability of that product during its dating period.
    We solicited comments on our proposed rule for 60 days ending on 
October 4, 2002. We received two comments by that date, from a 
veterinary biologics manufacturer and a national trade association 
representing veterinary biologics manufacturers. Both commenters 
supported the proposed rule. One commenter did, however, request that 
we ``clarify the exceptions to the use of the proposed method.'' The 
commenter recommended that if we intend to handle such instances via 
outline exemptions, then that should be stated. Additionally, the 
commenter asked that we indicate whether one valid reason for an 
exemption would be that a firm does not have the equipment necessary to 
conduct the test.
    In this final rule, we are adopting the gravimetric method as the 
standard procedure for determining moisture content. As a Standard 
Requirement test, the gravimetric method should be used whenever the 
test for moisture content is performed. However, we note that 
exemptions to the use of the gravimetric method, like exemptions to any 
test prescribed in the various standard requirements found in part 113, 
may be granted for any valid reason in accordance with Sec.  113.4, 
``Exemptions to tests.'' Exemption requests are evaluated on a product-
by-product basis, and in our review of such requests, we focus on the 
methods, equipment, and procedures that would be used in place of those 
prescribed in the Standard Requirement. It is the validity of the 
alternative methods and procedures that serves as the basis for the 
granting of an exemption.
    Therefore, for the reasons given in the proposed rule and in this 
document, we are adopting the proposed rule as a final rule, without 
change.

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 the purposes of Executive 
Order 12866 and, therefore, has not been reviewed by the Office of 
Management and Budget.
    We are amending the Virus-Serum-Toxin Act regulations for 
determination of moisture content in desiccated biological products to 
require that such moisture determinations be made using a gravimetric 
method that determines residual moisture by measuring the percentage of 
weight a product loses during a product drying cycle. In addition, this 
rule provides that the maximum percentage of moisture permitted for a 
satisfactory test must be specified in a filed Outline of Production. 
The effect of this action will be to provide a standardized method for 
the determination of moisture content in desiccated biological products 
that has been adopted internationally and ensure that such moisture 
determinations are uniform and reproducible.
    This rule will affect all licensed manufacturers of veterinary 
biologics that test desiccated vaccines for moisture content. 
Currently, there are approximately 135 veterinary biologics

[[Page 57608]]

establishments, including permittees. According to the standards of the 
Small Business Administration, most veterinary biologics establishments 
would be classified as small entities.
    We do not expect that this rule will impose any additional testing 
or economic burden on these manufacturers because manufacturers 
currently test their products for moisture content by methods specified 
in their filed Outline of Production and the reagents and equipment 
necessary to perform the gravimetric test for moisture content that 
will be required under this rule are expected to be comparable in cost.
    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 12988

    This final rule has been reviewed under Executive Order 12988, 
Civil Justice Reform. It is not intended to have retroactive effect. 
This rule will not preempt any State or local laws, regulations, or 
policies, unless they present an irreconcilable conflict with this 
rule. The Virus-Serum-Toxin Act does not provide administrative 
procedures which must be exhausted prior to a judicial challenge to the 
provisions of this rule.

Paperwork Reduction Act

    This final rule contains no new information or recordkeeping 
requirements under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 
et seq.).

List of Subjects in 9 CFR Part 113

    Animal biologics, Exports, Imports, Reporting and recordkeeping 
requirements.

0
Accordingly, we are amending 9 CFR part 113 as follows:

PART 113--[AMENDED]

0
1. The authority citation for part 113 continues to read as follows:

    Authority: 21 U.S.C. 151-159; 7 CFR 2.22, 2.80, and 371.4.


0
2. Section 113.29 is revised to read as follows:


Sec.  113.29  Determination of moisture content in desiccated 
biological products.

    Methods provided in this section must be used when a determination 
of moisture content in desiccated biological products is prescribed in 
an applicable Standard Requirement or in the filed Outline of 
Production for the product. Firms currently using methods other than 
those provided in this section for determining the moisture content in 
desiccated biological products have until November 5, 2004 to update 
their Outlines of Production to be in compliance with this requirement.
    (a) Final container samples of completed product shall be tested. 
The weight loss of the sample due to drying in a vacuum oven shall be 
determined. All procedures should be performed in an environment with a 
relative humidity less than 45 percent. The equipment necessary to 
perform the test is as follows:
    (1) Cylindrical weighing bottles with airtight glass stoppers.
    (2) Vacuum oven equipped with validated thermometer and thermostat. 
A suitable air-drying device should be attached to the inlet valve.
    (3) Balance, accurate to 0.1 mg (rated precision +/-0.01mg).
    (4) Desiccator jar equipped with phosphorous pentoxide, silica gel, 
or equivalent.
    (5) Desiccated vaccine in original sealed vial. Sample and control 
should be kept at room temperature in their original airtight 
containers until use.
    (b) Test procedure:
    (1) Thoroughly cleaned and labeled sample-weighing bottles with 
stoppers should be allowed to dry at 60 +/-3 [deg]C under vacuum at 
less than 2.5 kPa.
    (i) Transfer hot bottles and stoppers into the desiccator and allow 
to cool to room temperature.
    (ii) After bottles have cooled, insert stoppers and weigh and 
record the weights of the bottles as ``A.''
    (iii) Return weighing bottles to the desiccator.
    (2) Remove the sample container seal.
    (i) Using a spatula, break up the sample plug and transfer the 
required amount of sample to the previously tared weighing bottle.
    (ii) Insert the stopper and weigh and record the weights of the 
weighing bottles as ``B.''
    (3) Place the weighing bottle with the stopper at an angle in the 
vacuum oven. Set the vacuum to < 2.5 kPa and the temperature to 60 +/-3 
[deg]C.
    (4) After a minimum of 3 hours of drying time, turn off the vacuum 
pump and allow dry air to bleed into the oven until the pressure inside 
the oven is equalized with the prevailing atmospheric pressure.
    (5) While the bottle is still warm, replace the stopper in its 
normal position and transfer the weighing bottle to the desiccator.
    (i) Allow a minimum of 2 hours for the weighing bottle to cool to 
room temperature or for its weight to reach equilibrium.
    (ii) Weigh, and record the weight as ``C.''
    (6) Calculate the percentage of moisture in the original sample as 
follows:

(B-C)/(B-A) x (100) = Percentage of residual moisture, where:
A = tare weight of weighing bottle
B-A = weight of sample before drying
B-C = weight of sample after drying

    (7) The results are considered satisfactory if the percentage of 
residual moisture is less than or equal to the manufacturer's 
specification.

0
3. In Sec.  113.64, paragraph (e) is amended by adding a new paragraph 
(e)(3) to read as follows:


Sec.  113.64  General requirements for live bacterial vaccines.

* * * * *
    (e) * * *
    (3) Final container samples of completed product from each serial 
and subserial must be tested for moisture content in accordance with 
the test provided in Sec.  113.29.

0
4. Section 113.300 is amended by revising paragraph (e) to read as 
follows:


Sec.  113.300  General requirements for live virus vaccines.

* * * * *
    (e) Moisture content. (1) The maximum moisture content in 
desiccated vaccines must be stated in the filed Outline of Production.
    (2) Final container samples of completed product from each serial 
or subserial must be tested for moisture content in accordance with the 
test prescribed in Sec.  113.29.

    Done in Washington, DC, this 30th day of September 2003.
Kevin Shea,
Acting Administrator, Animal and Plant Health Inspection Service.
[FR Doc. 03-25251 Filed 10-3-03; 8:45 am]

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