Nomination of In Vitro Test Methods for Detection and Quantification of Botulinum Neurotoxins and Detection of Non-Endotoxin Pyrogens; Data Request for Substances Evaluated by These Test Methods, 29752-29754 [2011-12627]
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29752
Federal Register / Vol. 76, No. 99 / Monday, May 23, 2011 / Notices
GENERAL SERVICES
ADMINISTRATION
[Notice MC–2011–2; Docket No. 2011–0006;
Sequence 5]
The President’s Management Advisory
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Advisory Board, Office of Executive
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Administration, 1776 G Street NW.,
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stephen.brockelman@cxo.gov.
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agenda can be obtained from this Web
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SUMMARY:
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PO 00000
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Dated: May 16, 2011.
Robert Flaak,
Director, Office of Committee and Regulatory
Management, General Services
Administration.
[FR Doc. 2011–12647 Filed 5–20–11; 8:45 am]
BILLING CODE 6820–BR–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Nomination of In Vitro Test Methods
for Detection and Quantification of
Botulinum Neurotoxins and Detection
of Non-Endotoxin Pyrogens; Data
Request for Substances Evaluated by
These Test Methods
Division of National
Toxicology Program (NTP), National
Institute of Environmental Health
Sciences (NIEHS), National Institutes of
Health (NIH).
ACTION: Request for comments and/or
data.
AGENCY:
On behalf of the Interagency
Coordinating Committee on the
Validation of Alternative Methods
(ICCVAM), the NTP Interagency Center
for the Evaluation of Alternative
Toxicological Methods (NICEATM)
requests public comment on
nominations received for (1) Three in
vitro test methods proposed for
detecting and quantifying botulinum
neurotoxin (BoNT), and (2) an in vitro
test method proposed for detecting nonendotoxin pyrogens. NICEATM seeks
data generated using alternative test
methods for detecting and quantifying
BoNT, including but not limited to three
test methods nominated by BioSentinel
Pharmaceuticals, Inc. (BioSentinel).
Data from the standardized mouse LD50
assay currently used for these endpoints
are requested for comparison. In
addition, NICEATM seeks data
generated using alternative test methods
for identifying non-endotoxin pyrogens,
including but not limited to the
monocyte activation test (MAT), which
was nominated by Biotest AG. Data on
non-endotoxin pyrogens tested in the
rabbit pyrogen test (RPT) are requested
for comparison. NICEATM received
nominations for validation studies on
each of the above test methods, which
have the potential to reduce or replace
animal use for regulatory testing. At this
time, ICCVAM requests public
comments on the appropriateness and
relative priority of these activities.
DATES: For consideration by the
Scientific Advisory Committee on
Alternative Toxicological Methods
(SACATM) at its annual meeting (67 FR
23323), comments and data are
SUMMARY:
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Federal Register / Vol. 76, No. 99 / Monday, May 23, 2011 / Notices
srobinson on DSK4SPTVN1PROD with NOTICES
requested by June 2, 2011. NICEATM
and ICCVAM will accept comments and
data for these nominations until July 7,
2011.
Nomination for the Detection of NonEndotoxin Pyrogens
ICCVAM previously evaluated the
validation status of five in vitro test
methods proposed for assessing the
FOR FURTHER INFORMATION CONTACT: Dr.
potential pyrogenicity (i.e., ability to
Warren Casey, Deputy Director,
NICEATM, NIEHS, P.O. Box 12233, Mail induce fever) of pharmaceuticals and
other products, as potential
Stop: K2–16, Research Triangle Park,
replacements for the RPT. Subsequent to
NC, 27709, (telephone) 919–541–2384,
this evaluation, ICCVAM recommended
(fax) 919–541–0947, (e-mail)
that, although none of the test methods
niceatm@niehs.nih.gov. Courier
address: NICEATM, NIEHS, Room 2034, should be considered as a complete
530 Davis Drive, Morrisville, NC 27560. replacement for the RPT for the
detection of Gram-negative endotoxin,
SUPPLEMENTARY INFORMATION:
they can be considered for use to detect
Nomination for the Detection and
Gram-negative endotoxin in human
Quantification of BoNTs
parenteral drugs on a case-by-case basis,
subject to product-specific validation to
In 2006, NICEATM and ICCVAM
demonstrate equivalence to the RPT, in
convened a workshop, Alternative
accordance with applicable U.S. Federal
Methods to Refine, Reduce, or Replace
regulations (ICCVAM, 2008b). ICCVAM
the Mouse LD50 Assay for Botulinum
recognized that these test methods
Toxin Testing, in response to a
could be applicable for detection of a
nomination from the Humane Society of
wider range of pyrogens, including nonthe United States requesting that
endotoxin pyrogens, and made
ICCVAM assess the availability of
recommendations for future studies that
alternative methods to replace the
could expand their applicability. In
mouse LD50 assay for BoNT potency
response to these recommendations,
testing. Workshop participants
Biotest AG recently nominated a
concluded that some of the methods
commercialized version of one of these
considered could be used, in specific
tests (i.e., MAT), which uses
circumstances or in a tiered-testing
cryopreserved human blood and
strategy, to reduce or refine the use of
quantitates the induction of interleukin
mice in current in vivo BoNT testing
(IL)-1b, for additional validation studies
protocols (ICCVAM, 2008a). However,
to evaluate its usefulness for identifying
none of the reviewed methods was
non-endotoxin pyrogens.
considered suitable to serve as a
complete replacement for the mouse
Draft ICCVAM Conclusions and
LD50 assay, either for detection of BoNT Recommendations
or for potency determination. The
Based on the information provided by
workshop participants noted that some
the test method sponsors, ICCVAM
of the methods considered might be
concludes that the nominated activities
useful as replacements for the mouse
are of sufficient interest and
LD50 assay in the future given additional applicability to warrant further
development and validation efforts.
evaluation. ICCVAM’s preliminary
BioSentinel has developed tests for
recommendation is that both
the detection and quantification of
nominations should have a high priority
BoNTs. These tests include the in vitro
for further discussion to assess what
BoTestTM and BoTestTM Matrix assays
information is needed to adequately
and the cell-based assay BoCeIlTM.
characterize the usefulness and
Following appropriate validation and
limitations of the proposed test
demonstration of adequate performance, methods, and any other similar in vitro
these methods may have the potential to test methods, for these endpoints. These
meet regulatory requirements for
assessments will identify what data are
detection and quantification of BoNTs
needed and what studies are required to
in a range of applications.
fill any data gaps that are identified.
BioSentinel has forwarded a
Studies identified as necessary to
nomination for these methods to (1)
adequately characterize the validation
Facilitate collaboration to develop a
status for regulatory testing purposes are
validation strategy which could lead to
proposed to have a high priority.
As part of the nomination review
the regulatory acceptance of the test
process, NICEATM invites public
methods for the detection and
comments on these nominations and the
quantification of BoNT contained in
suspect substances, the determination of appropriateness and relative priority
assigned by ICCVAM to the nominated
drug product potency, and/or the
activities. ICCVAM will finalize its
clinical diagnosis of botulism and (2)
recommendations on the priority of
coordinate and conduct necessary
these nominations after considering
validation studies.
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29753
comments received from the public and
SACATM, which will comment on the
ICCVAM draft recommendations at its
meeting on June 16–17, 2011.
Background Information on ICCVAM,
NICEATM, and SACATM
ICCVAM is an interagency committee
composed of representatives from 15
Federal regulatory and research agencies
that require, use, generate, or
disseminate toxicological and safety
testing information. ICCVAM conducts
technical evaluations of new, revised,
and alternative safety testing methods
with regulatory applicability and
promotes the scientific validation and
regulatory acceptance of toxicological
and safety testing methods that more
accurately assess the safety and hazards
of chemicals and products and that
reduce, refine (decrease or eliminate
pain and distress), or replace animal
use. The ICCVAM Authorization Act of
2000 (42 U.S.C. 285l-3) established
ICCVAM as a permanent interagency
committee of the NIEHS under
NICEATM. NICEATM administers
ICCVAM, provides scientific and
operational support for ICCVAM-related
activities, and conducts independent
validation studies to assess the
usefulness and limitations of new,
revised, and alternative test methods
and strategies. NICEATM and ICCVAM
work collaboratively to evaluate new
and improved test methods and
strategies applicable to the needs of U.S.
Federal agencies. NICEATM and
ICCVAM welcome the public
nomination of new, revised, and
alternative test methods and strategies
for validation studies and technical
evaluations. Additional information
about ICCVAM and NICEATM can be
found on the NICEATM–ICCVAM Web
site (https://iccvam.niehs.vnih.gov).
SACATM was established in response
to the ICCVAM Authorization Act
(Section 285l–3(d)) and is composed of
scientists from the public and private
sectors. SACATM advises ICCVAM,
NICEATM, and the Director of the
NIEHS and NTP regarding statutorily
mandated duties of ICCVAM and
activities of NICEATM. SACATM
provides advice on priorities and
activities related to the development,
validation, scientific review, regulatory
acceptance, implementation, and
national and international
harmonization of new, revised, and
alternative toxicological test methods.
Additional information about SACATM,
including the charter, roster, and
records of past meetings, can be found
at https://ntp.niehs.nih.gov/go/167.
E:\FR\FM\23MYN1.SGM
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29754
Federal Register / Vol. 76, No. 99 / Monday, May 23, 2011 / Notices
References
ICCVAM. 2008a. ICCVAM–NICEATM/
ECVAM Scientific Workshop on Alternative
Methods to Refine, Reduce, or Replace the
Mouse LD50 Assay for Botulinum Toxin
Testing. NIH Publication No. 08–6416.
Research Triangle Park, NC: NIEHS.
Available: https://iccvam.niehs.nih.gov/docs/
biologics-docs/BoNTwkshprept.pdf.
ICCVAM. 2008b. ICCVAM Test Method
Evaluation Report: Validation Status of Five
In Vitro Test Methods Proposed for Assessing
Pyrogenicity of Pharmaceuticals and Other
Products. NIH Publication No. 08– 6392.
Research Triangle Park, NC: NIEHS.
Available: https://iccvam.niehs.nih.gov/
methods/pyrogen/pyr_tmer.htm.
Dated: May 16, 2011.
John R. Bucher,
Associate Director, National Toxicology
Program.
[FR Doc. 2011–12627 Filed 5–20–11; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Centers for Disease Control and
Prevention
[60-Day–11–0576]
Proposed Data Collections Submitted
for Public Comment and
Recommendations
In compliance with the requirement
of Section 3506(c)(2)(A) of the
Paperwork Reduction Act of 1995 for
opportunity for public comment on
proposed data collection projects, the
Centers for Disease Control and
Prevention (CDC) will publish periodic
summaries of proposed projects. To
request more information on the
proposed projects or to obtain a copy of
the data collection plans and
instruments, call 404–639–5960 and
send comments to Daniel Holcomb, CDC
Acting Reports Clearance Officer, 1600
Clifton Road, MS–D74, Atlanta, GA
30333 or send an e-mail to
omb@cdc.gov.
Comments are invited on: (a) Whether
the proposed collection of information
is necessary for the proper performance
of the functions of the agency, including
whether the information shall have
practical utility; (b) the accuracy of the
agency’s estimate of the burden of the
proposed collection of information; (c)
ways to enhance the quality, utility, and
clarity of the information to be
collected; and (d) ways to minimize the
burden of the collection of information
on respondents, including through the
use of automated collection techniques
or other forms of information
technology. Written comments should
be received within 60 days of this
notice.
Proposed Project
Possession, Use, and Transfer of
Select Agents and Toxins (OMB Control
No. 0920–0576)—Revision—Office of
Public Health Preparedness and
Response (OPHPR), Division of Select
Agents and Toxins, Centers for Disease
Control and Prevention (CDC).
Background and Brief Description
The Public Health Security and
Bioterrorism Preparedness and
Response Act of 2002, Subtitle A of
Public Law 107–188 (42 U.S.C. 262a),
requires the United States Department
of Health and Human Services (HHS) to
regulate the possession, use, and
transfer of biological agents or toxins
(i.e., select agents and toxins) that could
pose a severe threat to public health and
safety. The Agricultural Bioterrorism
Protection Act of 2002, Subtitle B of
Public Law 107–188 (7 U.S.C. 8401),
requires the United States Department
of Agriculture (USDA) to regulate the
possession, use, and transfer of
biological agents or toxins (i.e., select
agents and toxins) that could pose a
severe threat to animal or plant health,
or animal or plant products. In
accordance with these Acts, HHS and
USDA promulgated regulations
requiring entities to register with the
CDC or the Animal and Plant Health
Inspection Service (APHIS) if they
possess, use, or transfer a select agent or
toxin (42 CFR part 73, 7 CFR part 331,
and 9 CFR part 121).
CDC is requesting continued OMB
approval to collect this information
through the use of five forms: (1)
Application for Registration, (2) Request
to Transfer Select Agent or Toxin, (3)
Report of Theft, Loss, or Release of
Select Agent and Toxin, (4) Report of
Identification of Select Agent or Toxin,
and (5) Request for Exemption. There
have been no new select agent program
forms added to this information
collection request. The current versions
of the standard forms have been revised
to: (1) Reduce the burden expended by
the regulated entities and CDC by
removing similar questions, (2) enhance
clarification of the transfer process, (3)
determine the level of potential
exposure, and (4) improve surveillance
methods for monitoring the reports of
select agents and toxins identified by
registered entities. In addition to the
standardized forms listed above,
requests for expedited reviews,
administrative reviews and inspections
are also submitted to CDC. There is not
a standardized form for the request for
expedited review, administrative review
and inspections. Therefore, an entity
must submit a written request to the
Secretary of Health and Human
Services, by way of the Attorney
General for expedited reviews (42 CFR
73.10(e)) and exclusions of an
attenuated strain of a select agent or
toxin that does not pose a severe threat
to public health and safety (42 CFR
73.3(e)(1) and 73.4(e)(1)). Inspections
take place prior to issuance of a
certificate of registration to ensure
compliance with regulation 42 CFR
73.18. Following the inspection an
entity may be asked to respond to
written requests and submits the
documentation to CDC.
Entities may also amend their
registration (42 CFR, 73.7(h)(1)) if any
changes occur to the information
previously submitted. When applying
for an amendment to a certificate of
registration, an entity must obtain and
complete the relevant portion of the
application package.
The total estimated annualized
burden for all data collection is 8,878
hours. Information will be collected via
fax, email and mail from respondents of
the 320 entities registered with the
Select Agent Program. There is no cost
to the respondents other than their time.
srobinson on DSK4SPTVN1PROD with NOTICES
ESTIMATED ANNUALIZED BURDEN HOURS
Form name
73.3(d) .............................................
73.7(h)(1) ........................................
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Average burden
per response
5
320
1
8
4.5
1
23
2,560
320
Application for Registration ............
Amendment to Registration Application.
Request to Transfer Select Agents
or Toxins.
73.16 ...............................................
Number of responses per
respondent
1
1.5
480
Number of
respondents
CFR
Fmt 4703
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E:\FR\FM\23MYN1.SGM
23MYN1
Total burden
hours
Agencies
[Federal Register Volume 76, Number 99 (Monday, May 23, 2011)]
[Notices]
[Pages 29752-29754]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-12627]
=======================================================================
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Nomination of In Vitro Test Methods for Detection and
Quantification of Botulinum Neurotoxins and Detection of Non-Endotoxin
Pyrogens; Data Request for Substances Evaluated by These Test Methods
AGENCY: Division of National Toxicology Program (NTP), National
Institute of Environmental Health Sciences (NIEHS), National Institutes
of Health (NIH).
ACTION: Request for comments and/or data.
-----------------------------------------------------------------------
SUMMARY: On behalf of the Interagency Coordinating Committee on the
Validation of Alternative Methods (ICCVAM), the NTP Interagency Center
for the Evaluation of Alternative Toxicological Methods (NICEATM)
requests public comment on nominations received for (1) Three in vitro
test methods proposed for detecting and quantifying botulinum
neurotoxin (BoNT), and (2) an in vitro test method proposed for
detecting non-endotoxin pyrogens. NICEATM seeks data generated using
alternative test methods for detecting and quantifying BoNT, including
but not limited to three test methods nominated by BioSentinel
Pharmaceuticals, Inc. (BioSentinel). Data from the standardized mouse
LD50 assay currently used for these endpoints are requested
for comparison. In addition, NICEATM seeks data generated using
alternative test methods for identifying non-endotoxin pyrogens,
including but not limited to the monocyte activation test (MAT), which
was nominated by Biotest AG. Data on non-endotoxin pyrogens tested in
the rabbit pyrogen test (RPT) are requested for comparison. NICEATM
received nominations for validation studies on each of the above test
methods, which have the potential to reduce or replace animal use for
regulatory testing. At this time, ICCVAM requests public comments on
the appropriateness and relative priority of these activities.
DATES: For consideration by the Scientific Advisory Committee on
Alternative Toxicological Methods (SACATM) at its annual meeting (67 FR
23323), comments and data are
[[Page 29753]]
requested by June 2, 2011. NICEATM and ICCVAM will accept comments and
data for these nominations until July 7, 2011.
FOR FURTHER INFORMATION CONTACT: Dr. Warren Casey, Deputy Director,
NICEATM, NIEHS, P.O. Box 12233, Mail Stop: K2-16, Research Triangle
Park, NC, 27709, (telephone) 919-541-2384, (fax) 919-541-0947, (e-mail)
niceatm@niehs.nih.gov. Courier address: NICEATM, NIEHS, Room 2034, 530
Davis Drive, Morrisville, NC 27560.
SUPPLEMENTARY INFORMATION:
Nomination for the Detection and Quantification of BoNTs
In 2006, NICEATM and ICCVAM convened a workshop, Alternative
Methods to Refine, Reduce, or Replace the Mouse LD50 Assay
for Botulinum Toxin Testing, in response to a nomination from the
Humane Society of the United States requesting that ICCVAM assess the
availability of alternative methods to replace the mouse
LD50 assay for BoNT potency testing. Workshop participants
concluded that some of the methods considered could be used, in
specific circumstances or in a tiered-testing strategy, to reduce or
refine the use of mice in current in vivo BoNT testing protocols
(ICCVAM, 2008a). However, none of the reviewed methods was considered
suitable to serve as a complete replacement for the mouse
LD50 assay, either for detection of BoNT or for potency
determination. The workshop participants noted that some of the methods
considered might be useful as replacements for the mouse
LD50 assay in the future given additional development and
validation efforts.
BioSentinel has developed tests for the detection and
quantification of BoNTs. These tests include the in vitro
BoTestTM and BoTestTM Matrix assays and the cell-
based assay BoCeIlTM. Following appropriate validation and
demonstration of adequate performance, these methods may have the
potential to meet regulatory requirements for detection and
quantification of BoNTs in a range of applications.
BioSentinel has forwarded a nomination for these methods to (1)
Facilitate collaboration to develop a validation strategy which could
lead to the regulatory acceptance of the test methods for the detection
and quantification of BoNT contained in suspect substances, the
determination of drug product potency, and/or the clinical diagnosis of
botulism and (2) coordinate and conduct necessary validation studies.
Nomination for the Detection of Non-Endotoxin Pyrogens
ICCVAM previously evaluated the validation status of five in vitro
test methods proposed for assessing the potential pyrogenicity (i.e.,
ability to induce fever) of pharmaceuticals and other products, as
potential replacements for the RPT. Subsequent to this evaluation,
ICCVAM recommended that, although none of the test methods should be
considered as a complete replacement for the RPT for the detection of
Gram-negative endotoxin, they can be considered for use to detect Gram-
negative endotoxin in human parenteral drugs on a case-by-case basis,
subject to product-specific validation to demonstrate equivalence to
the RPT, in accordance with applicable U.S. Federal regulations
(ICCVAM, 2008b). ICCVAM recognized that these test methods could be
applicable for detection of a wider range of pyrogens, including non-
endotoxin pyrogens, and made recommendations for future studies that
could expand their applicability. In response to these recommendations,
Biotest AG recently nominated a commercialized version of one of these
tests (i.e., MAT), which uses cryopreserved human blood and quantitates
the induction of interleukin (IL)-1[beta], for additional validation
studies to evaluate its usefulness for identifying non-endotoxin
pyrogens.
Draft ICCVAM Conclusions and Recommendations
Based on the information provided by the test method sponsors,
ICCVAM concludes that the nominated activities are of sufficient
interest and applicability to warrant further evaluation. ICCVAM's
preliminary recommendation is that both nominations should have a high
priority for further discussion to assess what information is needed to
adequately characterize the usefulness and limitations of the proposed
test methods, and any other similar in vitro test methods, for these
endpoints. These assessments will identify what data are needed and
what studies are required to fill any data gaps that are identified.
Studies identified as necessary to adequately characterize the
validation status for regulatory testing purposes are proposed to have
a high priority.
As part of the nomination review process, NICEATM invites public
comments on these nominations and the appropriateness and relative
priority assigned by ICCVAM to the nominated activities. ICCVAM will
finalize its recommendations on the priority of these nominations after
considering comments received from the public and SACATM, which will
comment on the ICCVAM draft recommendations at its meeting on June 16-
17, 2011.
Background Information on ICCVAM, NICEATM, and SACATM
ICCVAM is an interagency committee composed of representatives from
15 Federal regulatory and research agencies that require, use,
generate, or disseminate toxicological and safety testing information.
ICCVAM conducts technical evaluations of new, revised, and alternative
safety testing methods with regulatory applicability and promotes the
scientific validation and regulatory acceptance of toxicological and
safety testing methods that more accurately assess the safety and
hazards of chemicals and products and that reduce, refine (decrease or
eliminate pain and distress), or replace animal use. The ICCVAM
Authorization Act of 2000 (42 U.S.C. 285l-3) established ICCVAM as a
permanent interagency committee of the NIEHS under NICEATM. NICEATM
administers ICCVAM, provides scientific and operational support for
ICCVAM-related activities, and conducts independent validation studies
to assess the usefulness and limitations of new, revised, and
alternative test methods and strategies. NICEATM and ICCVAM work
collaboratively to evaluate new and improved test methods and
strategies applicable to the needs of U.S. Federal agencies. NICEATM
and ICCVAM welcome the public nomination of new, revised, and
alternative test methods and strategies for validation studies and
technical evaluations. Additional information about ICCVAM and NICEATM
can be found on the NICEATM-ICCVAM Web site (https://iccvam.niehs.vnih.gov).
SACATM was established in response to the ICCVAM Authorization Act
(Section 285l-3(d)) and is composed of scientists from the public and
private sectors. SACATM advises ICCVAM, NICEATM, and the Director of
the NIEHS and NTP regarding statutorily mandated duties of ICCVAM and
activities of NICEATM. SACATM provides advice on priorities and
activities related to the development, validation, scientific review,
regulatory acceptance, implementation, and national and international
harmonization of new, revised, and alternative toxicological test
methods. Additional information about SACATM, including the charter,
roster, and records of past meetings, can be found at https://ntp.niehs.nih.gov/go/167.
[[Page 29754]]
References
ICCVAM. 2008a. ICCVAM-NICEATM/ECVAM Scientific Workshop on
Alternative Methods to Refine, Reduce, or Replace the Mouse
LD50 Assay for Botulinum Toxin Testing. NIH Publication
No. 08-6416. Research Triangle Park, NC: NIEHS. Available: https://iccvam.niehs.nih.gov/docs/biologics-docs/BoNTwkshprept.pdf.
ICCVAM. 2008b. ICCVAM Test Method Evaluation Report: Validation
Status of Five In Vitro Test Methods Proposed for Assessing
Pyrogenicity of Pharmaceuticals and Other Products. NIH Publication
No. 08- 6392. Research Triangle Park, NC: NIEHS. Available: https://iccvam.niehs.nih.gov/methods/pyrogen/pyr_tmer.htm.
Dated: May 16, 2011.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2011-12627 Filed 5-20-11; 8:45 am]
BILLING CODE 4140-01-P