[Federal Register Volume 71, Number 238 (Tuesday, December 12, 2006)]
[Notices]
[Pages 74533-74534]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-21038]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES


National Toxicology Program (NTP), NTP Interagency Center for the 
Evaluation of Alternative Toxicological Methods (NICEATM); Announcement 
of an Independent Scientific Peer Review Meeting on the Use of In Vitro 
Pyrogenicity Testing Methods; Request for Comments

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

ACTION: Meeting announcement and request for comments.

-----------------------------------------------------------------------

SUMMARY: NICEATM in collaboration with the Interagency Coordinating 
Committee on the Validation of Alternative Methods (ICCVAM) announces 
an independent scientific peer review meeting 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). These five in vitro test methods are 
proposed as replacements for the in vivo rabbit pyrogen test (RPT). At 
this meeting, a scientific panel will peer review the draft background 
review document (BRD) on each test method, evaluate the extent that the 
BRD addresses established validation and acceptance criteria for each 
test method, and provide comment on draft ICCVAM recommendations on the 
proposed use of these test methods, draft test method protocols, and 
draft performance standards. NICEATM invites public comments on the 
draft BRDs, draft ICCVAM test method recommendations, draft test method 
protocols, and draft performance standards.

DATES: The meeting will be held on February 6, 2007, from 8:30 a.m. to 
5 p.m. The meeting is open to the public with attendance limited only 
by the space available. In order to facilitate planning for this 
meeting, persons wishing to attend are asked to register by January 23, 
2007, via the ICCVAM/NICEATM Web site (http://iccvam.niehs.nih.gov). 
Comments should be sent by mail, fax, or email to the address given 
below by January 26, 2007.

ADDRESSES: The meeting will be held at the National Institutes of 
Health (NIH), Natcher Conference Center, 45 Center Drive, Bethesda, MD 
20892.

FOR FURTHER INFORMATION CONTACT: Dr. William S. Stokes, Director of 
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]. Courier address: NICEATM, 79 T.W. Alexander 
Drive, Building 4401, Room 3128, Research Triangle Park, NC 27709.

SUPPLEMENTARY INFORMATION:

Background

    The European Centre for the Validation of Alternative Methods 
(ECVAM) conducted a validation study to independently evaluate the 
usefulness and limitations of five in vitro pyrogenicity test methods 
(PBMC/IL-6, WB/IL-1, cryo WB/IL-1, WB/IL-6, and MM6/IL6). In June 2005, 
ECVAM submitted BRDs for these five methods to NICEATM for 
consideration as replacements for the currently required test, the RPT. 
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 that the sponsor needed to 
provide additional information prior to a formal scientific review by 
an expert panel. In anticipation of proceeding with an evaluation of 
these test methods, ICCVAM and NICEATM requested public comments as to 
the appropriateness and relative priority of a panel review activity 
and the nomination of scientists with relevant knowledge and experience 
to potentially serve on the panel (Federal Register Vol. 70, No. 241, 
pp. 74833-4, December 16, 2005). NICEATM also requested submission of 
data using the standard in vivo rabbit pyrogen test, the bacterial 
endotoxin test (BET), and in vitro pyrogenicity tests. These requests 
were sent directly to over 100 interested stakeholders; no additional 
data were received.
    In March 2006, ECVAM responded to the ICCVAM/NICEATM request for 
information by providing a revised BRD for each test method. ICCVAM and 
NICEATM drafted a BRD that combines all of the available information on 
the five in vitro pyrogenicity test methods into a single document and 
includes each of the ECVAM BRDs as an appendix. Based on this 
information, ICCVAM developed draft test method recommendations 
regarding the proposed usefulness, limitations, and validation status 
of these test methods. ICCVAM subsequently recommended that an 
independent scientific panel be convened to (1) peer review the draft 
BRD for the test methods and (2) determine whether the data and 
analyses in the draft BRDs support the draft ICCVAM test method 
recommendations. The panel will also be asked to comment on the 
adequacy of the draft recommended performance standards, proposed 
future validation studies, draft standardized test method protocols, 
and recommended reference substances. In making their conclusions and 
recommendations, NICEATM will ask the panel to consider all available 
information including the scientific studies cited in the draft BRD, 
public comments, and any new information identified during the peer 
review.

Peer Review Panel Meeting

    The purpose of this meeting is the scientific peer review 
evaluation of the validation status of five in vitro pyrogenicity test 
methods as replacements for the RPT. First, the panel will review the 
draft BRD on the current status of five in vitro test methods for the 
detection of pyrogenicity and evaluate the extent that established 
validation and acceptance criteria are addressed for each test method 
(Validation and Regulatory Acceptance of Toxicological Test Methods: A 
Report of the ad hoc Interagency Coordinating Committee on the 
Validation of Alternative Methods, NIH Publication No. 97-981, http://iccvam.niehs.nih.gov). Next, the panel will comment on the extent to 
which the ICCVAM recommendations are supported by the information 
provided in the BRD and on the proposed use of these test methods, 
draft test method protocols, draft performance standards, and any 
proposed validation studies.
    Information about the panel meeting, including a roster of the 
panel members and the draft agenda, will be made available two weeks 
prior to the meeting on the ICCVAM/NICEATM Web site (http://iccvam.niehs.nih.gov) or can be

[[Page 74534]]

obtained after that date by contacting NICEATM (see FOR FURTHER 
INFORMATION CONTACT above).

Attendance and Registration

    This public meeting will take place February 6, 2007, at the NIH 
Campus, Natcher Conference Center, Bethesda, MD (a map of the NIH 
campus and other visitor information are available at http://www.nih.gov/about/visitor/index.htm). The meeting begins at 8:30 a.m. 
and will conclude at approximately 5 p.m. Persons needing special 
assistance, such as sign language interpretation or other reasonable 
accommodation in order to attend, should contact 919-541-2475 (voice), 
919-541-4644 TTY (text telephone), through the Federal TTY Relay System 
at 800-877-8339, or by e-mail to [email protected]. Requests 
should be made at least seven business days in advance of the event.

Availability of the BRD and Draft ICCVAM Recommendations

    NICEATM prepared a BRD on five in vitro pyrogenicity test methods 
that describes the current validation status of the in vitro test 
methods and contains all of the data and analyses supporting this 
validation status. The draft BRDs, draft ICCVAM test method 
recommendations, draft test method protocols, and draft test method 
performance standards are available from the ICCVAM/NICETAM Web site 
(http://iccvam.niehs.nih.gov) or by contacting NICEATM (see FOR FURTHER 
INFORMATION CONTACT above).

Request for Comments

    NICEATM invites the submission of written comments on the BRDs, 
draft ICCVAM test method recommendations, draft test method protocols, 
and draft test method performance standards. When submitting written 
comments, it is important to refer to this Federal Register notice and 
include appropriate contact information (name, affiliation, mailing 
address, phone, fax, e-mail, and sponsoring organization, if 
applicable). Written comments should be sent by mail, fax, or e-mail to 
Dr. William Stokes, Director of NICEATM, at the address listed above, 
not later than January 26, 2007. All comments received will be placed 
on the ICCVAM/NICEATM Web site (http://iccvam.niehs.nih.gov), sent to 
the panel and ICCVAM agency representatives, and made available at the 
meeting.
    This meeting is open to the public and time will be provided for 
the presentation of public oral comments at designated times during the 
peer review. Members of the public who wish to present oral statements 
at the meeting (one speaker per organization) should contact NICEATM 
(see FOR FURTHER INFORMATION CONTACT above) no later than January 26, 
2007. Speakers will be assigned on a consecutive basis and up to seven 
minutes will be allotted per speaker. Persons registering to make 
comments are asked to provide NICEATM a written copy of their statement 
by January 26, 2007, so that copies can be distributed to the panel 
prior to the meeting or if this is not possible to bring 40 copies to 
the meeting. Written statements can supplement and expand the oral 
presentation. Each speaker is asked to provide contact information 
(name, affiliation, mailing address, phone, fax, e-mail, and sponsoring 
organization, if applicable) when registering to make oral comments.
    Summary minutes and the panel's final report will be available 
following the meeting on the ICCVAM/NICEATM Web site (http://iccvam.niehs.nih.gov). ICCVAM will consider the panel's conclusions and 
recommendations and any public comments received in finalizing their 
test method recommendations and performance standards for these 
methods.

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, and replace 
animal use. The ICCVAM Authorization Act of 2000 (42 U.S.C. 285l-3, 
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 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://iccvam.niehs.nih.gov.

    Dated: November 27, 2006.
Samuel H. Wilson,
Deputy Director, National Institute of Environmental Health Sciences 
and National Toxicology Program.
[FR Doc. E6-21038 Filed 12-11-06; 8:45 am]
BILLING CODE 4140-01-P