[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]
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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.
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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.
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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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