National Toxicology Program (NTP), NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM); Peer Review Panel Report on Five In Vitro Pyrogen Test Methods: Availability and Request for Public Comments

AGENCY:

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

ACTION:

Request for comments.

SUMMARY:

NICEATM in collaboration with the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) convened an independent scientific peer review panel meeting on February 6, 2007, to evaluate the validation status of five in vitro pyrogen test methods proposed as replacements for the Rabbit Pyrogen Test (RPT). The peer review panel (“the Panel”) report from this meeting is now available. The report contains (1) the Panel's evaluation of the validation status of the methods and (2) the Panel's comments and conclusions on draft ICCVAM test method recommendations. NICEATM invites public comment on the Panel's report. The report is available on the NICEATM/ICCVAM Web site at ( http://iccvam.niehs.nih.gov/methods/pyrogen/pyrogen.htm ) or by contacting NICEATM (see FOR FURTHER INFORMATION CONTACT below).

DATES:

Written comments on the Panel report should be received by June 25, 2007.

ADDRESSES:

Comments should preferably be submitted electronically via the NICEATM/ICCVAM Web site: http://iccvam.niehs.nih.gov/contact/FR_pubcomment.htm . Comments can also be submitted by e-mail to niceatm@niehs.nih.gov. Written comments can be sent by mail or fax to Dr. William S. Stokes, NICEATM Director, NIH/NIEHS, P.O. Box 12233, MD EC-17, Research Triangle Park, NC 27709, (fax) 919-541-0947, (e-mail) niceatm@niehs.nih.gov. Courier address: NICEATM, 79 T.W. Alexander Drive, Building 4401, Room 3128, Research Triangle Park, NC 27709.

FOR FURTHER INFORMATION CONTACT:

Other correspondence should be directed to Dr. William S. Stokes, NICEATM Director (919-541-2384 or niceatm@niehs.nih.gov).

SUPPLEMENTARY INFORMATION

Background

The European Centre for the Validation of Alternative Methods (ECVAM) submitted five in vitro pyrogen test methods to ICCVAM for evaluation in 2006. The proposed test methods include:

1. The Human Whole Blood (WB)/IL-1 In Vitro Pyrogen Test: Application of Cryopreserved Human WB

2. The Monocytoid Cell Line Mono Mac 6 (MM6)/IL-6 In Vitro Pyrogen Test

3. The Human PBMC/IL-6 In Vitro Pyrogen Test

4. The Human WB/IL-1 In Vitro Pyrogen Test

5. The Human WB/IL-6 In Vitro Pyrogen Test

These test methods are based on the measurement of proinflammatory cytokines released from either fresh or cryopreserved human blood cells or a human monocytoid line in response to the presence of Gram-negative endotoxin in parenteral pharmaceuticals. NICEATM and ICCVAM prepared a comprehensive background review document (BRD) that included the available data for the five test methods and a separate document containing ICCVAM test method recommendations. At the peer review meeting, the Panel reviewed the BRD and evaluated the extent to which the ICCVAM criteria for validation and acceptance had been adequately addressed for the intended purpose of these test methods. The Panel also provided comments on the ICCVAM draft test method recommendations regarding the proposed usefulness and limitations, standardized protocols, performance standards, and future studies. The Panel's conclusions and recommendations on the five in vitro pyrogen test methods are described in the Peer Review Panel Final Report: Five In Vitro Pyrogen Test Methods (available at: http://iccvam.niehs.nih.gov/methods/pyrogen/pyrogen.htm ). The draft BRD and the draft test method recommendations are available at http://iccvam.niehs.nih.gov/methods/pyrogen/pyrogen.htm.

Request for Comments

NICEATM invites the submission of written comments on the Panel's report. When submitting written comments please refer to this Federal Register notice and include appropriate contact information (name, affiliation, mailing address, phone, fax, email, and sponsoring organization, if applicable). All comments received by the deadline listed above will be placed on the NICEATM/ICCVAM Web site ( http://ntp-apps.niehs.nih.gov/iccvampb/searchPubCom.cfm ) and made available to ICCVAM. In addition, there will be an opportunity for oral public comments on the Panel's report during a meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) scheduled for June 12, 2007. Information concerning the SACATM meeting will be published in a separate Federal Register notice and available on the SACATM website: ( http://ntp.niehs.nih.gov/go/7441 ). Any written comments on the Panel report received prior to June 7, 2007, will be distributed to SACATM.

ICCVAM will consider the Panel report along with the SACATM and public comments as it finalizes recommendations for the five in vitro pyrogen test methods. An ICCVAM test method evaluation report, which includes the ICCVAM final recommendations, will be forwarded to appropriate federal agencies for their consideration. This report will also be available to the public on the NICEATM/ICCVAM Web site and by request from NICEATM.

Background Information on ICCVAM, NICEATM, and SACATM

ICCVAM is an interagency committee composed of representatives from 15 federal regulatory and research agencies that use, generate, or disseminate toxicological information. ICCVAM conducts technical evaluations of new, revised, and alternative methods with regulatory applicability and promotes scientific validation and regulatory acceptance of toxicological test methods that more accurately assess safety and hazards of chemicals and products and that refine, reduce, and replace animal use. The ICCVAM Authorization Act of 2000 (42 U.S.C. 285l-3, available at http://iccvam.niehs.nih.gov/docs/about_docs/PL106545.pdf ) establishes ICCVAM as a permanent interagency committee of the NIEHS under NICEATM. NICEATM administers 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 ICCVAM/NICEATM Web site ( http://iccvam.niehs.nih.gov ).

Additional information about SACATM, including the charter, roster, and records of past meetings, can be found at http://ntp.niehs.nih.gov/go/167 .