E5-7410. 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 ...

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.

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) [e-mail].

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 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.