[Federal Register Volume 70, Number 241 (Friday, December 16, 2005)]
[Notices]
[Pages 74833-74834]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E5-7410]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES


National Toxicology Program (NTP), NTP Interagency Center for the 
Evaluation of Alternative Toxicological Methods (NICEATM); Peer Panel 
Evaluation of In Vitro Pyrogenicity Testing Methods: Request for 
Comments, Nominations of Experts, and Submission of In Vivo and In 
Vitro Data

AGENCY: National Institute of Environmental Health Sciences (NIEHS), 
National Institutes Of Health (NIH).

ACTION: Request for comments, nominations of scientific experts, and 
submission of data.

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SUMMARY: NICEATM, in collaboration with the Interagency Coordinating 
Committee on the Validation of Alternative Methods (ICCVAM), is 
considering convening an independent peer review panel (hereafter, 
``Panel'') to evaluate the validation status of five in vitro 
pyrogenicity test methods: (1) Human PBMC/IL-6 in vitro pyrogen test 
(PBMC/IL-6), (2) human whole blood/IL-1 in vitro pyrogen test (WB/IL-
1), (3) human whole blood/IL-1 in vitro pyrogen test: application of 
cryopreserved human whole blood cryo (WB/IL-1), (4) the human whole 
blood/IL-6 in vitro pyrogen test (WB/IL-6), and (5) an alternative in 
vitro pyrogen test using the human monocytoid cell line MONO MAC-6 
(MM6/IL6). NICEATM requests public comments as to the appropriateness 
and relative priority of this activity. In addition, NICEAM requests 
the nomination of expert scientists for consideration as potential 
Panel members in the event a Panel meeting occurs. Finally, NICEATM 
requests the submission of data from the rabbit pyrogenicity test, the 
bacterial endotoxin test (BET), and in vitro pyrogenicity testing with 
the methods listed above.

DATES: Comments, nominations of expert scientist, and data submissions 
should be received by January 17, 2006.

ADDRESSES: Correspondence should be sent by mail, fax, or email to Dr. 
William S. Stokes, NICEATM, NIEHS, P. O. Box 12233, MD EC-17, Research 
Triangle Park, NC, 27709, (phone) 919-541-2384, (fax) 919-541-0947, (e-
mail) [email protected].

SUPPLEMENTARY INFORMATION:

Background

    The European Committee on the Validation of Alternative Methods 
(ECVAM) conducted a validation study to independently evaluate the 
usefulness of five in vitro pyrogenicity assays (PBMC/IL-6, WB/IL-1, 
cryo WB/IL-1, WB/IL-6, and MM6/IL6). In June 2005, ECVAM submitted 
background review documents (BRDs) for these five methods to NICEATM 
for consideration as replacements for the currently required tests 
(i.e., rabbit pyrogen tests and the BET). ICCVAM and NICEATM reviewed 
the BRDs for completeness and concluded that these five in vitro test 
methods appear to have considerable potential for pyrogenicity testing, 
but the sponsors needed to provide additional information prior to a 
formal review by a Panel. Pending receipt and review of the requested 
information, ICCVAM and NICEATM will determine the priority of an 
evaluation of these test methods. If convened, the Panel would (1) peer 
review the BRDs for the test methods, and (2) determine whether the 
data cited in the BRDs support draft ICCVAM Test Method Recommendations 
regarding the proposed usefulness, limitations, and validation status 
of the test methods. If appropriate, the Panel might also formulate 
conclusions on the adequacy of any draft recommended performance 
standards, any proposed future validation studies, draft standardized 
test method protocols, and/or reference substances. In making their 
conclusions and recommendations, the Panel considers all available 
information including the scientific studies cited in the draft BRD, 
public comments, and any new information identified during the peer 
review.

Request for Public Comments and Nominations of Scientific Experts

    NICEATM requests public comments on the appropriateness and 
relative priority of the proposed Panel review activity. In addition, 
NICEAM requests the nomination of scientists with relevant knowledge 
and experience to potentially serve on the Panel should it be convened. 
Areas of relevant expertise include, but are not limited to: 
physiology, pharmacology, immunology, pyrogenicity testing in animals, 
development and use of in vitro methodologies, biostatistical data 
analysis, knowledge of chemical data sets useful for validation of 
toxicity studies, and hazard classification of chemicals and products. 
Each nomination should include the person's name, affiliation, contact 
information (i.e., mailing address, e-mail address, telephone and fax 
numbers), and a brief summary of relevant experience and 
qualifications.

Request for Data

    NICEATM invites the submission of data from standard in vivo rabbit 
pyrogen testing, the BET, and in vitro pyrogenicity testing using the 
methods detailed above. Although data can be accepted at any time, data 
submitted by the deadline listed in this notice would be considered 
during an evaluation of the validation status of the five pyrogenicity 
testing methods should this activity occur. Submitted data will be used 
to further evaluate the usefulness and limitations of in vitro 
pyrogenicity test methods and may be included in future NICEATM and 
ICCVAM reports and publications as appropriate. The data will also be 
included in a NICEATM database to support the investigation of other 
test methods for assessing pyrogenicity.
    When submitting chemical and protocol information/test data, please 
reference this Federal Register notice and provide appropriate contact 
information (name, affiliation, mailing address, phone, fax, e-mail, 
and sponsoring organization, as applicable).
    NICEATM prefers data to be submitted as copies of pages from study 
notebooks and/or study reports, if available. Raw data and analyses 
available in electronic format may also be submitted. Each submission 
for a chemical should preferably include the following information, as 
appropriate:

 Common and trade name
 Chemical Abstracts Service Registry Number (CASRN)
 Chemical class
 Product class
 Commercial source
 In vitro pyrogenicity test protocol used
 In vitro pyrogenicity test results
 BET test protocol used
 BET test results
 In vivo rabbit pyrogen test protocol used
 Individual animal responses
 The extent to which the study complied with national or 
international Good Laboratory Practice (GLP) guidelines
 Date and testing organization

Background Information on ICCVAM and NICEATM

    ICCVAM is an interagency committee composed of representatives from 
15 Federal regulatory and research agencies that use or generate 
toxicological information. ICCVAM conducts technical evaluations of 
new, revised, and alternative methods with regulatory applicability and 
promotes the scientific validation and regulatory acceptance of 
toxicological test methods that more

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accurately assess the safety and hazards of chemicals and products and 
that refine, reduce, or replace animal use. The ICCVAM Authorization 
Act of 2000 (Pub. L. 106-545, available at http://iccvam.niehs.nih.gov/about/PL106545.htm) establishes ICCVAM as a permanent interagency 
committee of the NIEHS under the NICEATM. NICEATM administers the 
ICCVAM and provides scientific and operational support for ICCVAM-
related activities. NICEATM and ICCVAM work collaboratively to evaluate 
new and improved test methods applicable to the needs of Federal 
agencies. Additional information about ICCVAM and NICEATM can be found 
at the following Web site: http://www.iccvam.niehs.nih.gov.

    Dated: Decmeber 5, 2005.
Samuel H. Wilson,
Deputy Director, National Institute of Environmental Health Sciences.
[FR Doc. E5-7410 Filed 12-15-05; 8:45 am]
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