[Federal Register Volume 62, Number 207 (Monday, October 27, 1997)]
[Notices]
[Pages 55649-55651]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-28373]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


National Institute of Environmental Health Sciences (NIEHS); 
Notice of Meeting To Discuss the Procedures and Activities of the 
National Toxicology Program (NTP) Center for the Evaluation of 
Alternative Toxicological Methods and the Interagency Coordinating 
Committee on the Validation of Alternative Methods (ICCVAM)

Summary: Pursuant to Public Law 103-43, notice is hereby given of a 
public meeting sponsored by the NIEHS and the NTP, U.S. Public Health 
Service, to discuss the planned procedures and activities of a new NTP 
Center for the Evaluation of Alternative Toxicological Methods and the 
ICCVAM, and to receive comments from invited participants and the 
public to assist with future activities and priorities.
    The meeting will be held in the Conference Center, Building 101, 
South Campus, NIEHS, 111 Alexander Drive, Research Triangle Park, North 
Carolina 27709, on November 7, 1997, from 8:45 a.m. to 4:00 p.m.
    Background Information: Public Law 103-43 directed the NIEHS to 
develop and validate alternative methods that

[[Page 55650]]

can reduce or eliminate the use of animals in acute or chronic toxicity 
testing, establish criteria for the validation and regulatory 
acceptance of alternative testing methods, and recommend a process 
through which scientifically validated alternative methods can be 
accepted for regulatory use. Criteria and processes for validation and 
regulatory acceptance were developed in conjunction with 14 other 
Federal agencies and programs with broad input and participation from 
the public. These are described in the document ``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 97-3981, March 1997. The 
Report's recommendations include the establishment of an interagency 
coordinating committee whose functions would include the coordination 
of interagency reviews of toxicological test methods and communication 
with stakeholders throughout the process of test method development and 
validation. In response to these recommendations, the NIEHS, in 
collaboration with 13 other Federal agencies and programs, recently 
established the Interagency Coordinating Committee on the Validation of 
Alternative Methods (ICCVAM). The ICCVAM is composed of representatives 
from NTP Executive Committee agencies and several other federal 
regulatory and research agencies. The ICCVAM addresses toxicological 
test method issues that are common to multiple agencies without 
impinging on considerations unique to individual programs and agencies. 
Coordinated test method peer reviews are expected to facilitate the 
acceptance decision process, with final regulatory acceptance 
recognized as the purview of each Federal agency according to its 
regulatory mandates.
    A NTP Center for the Evaluation of Alternative Toxicological 
Methods is being established to work with ICCVAM to carry out related 
activities and to implement the Report's recommendations. The Center 
proposal includes the opportunity for public-private partnerships to 
enhance the level and scope of the Center's activities. The planned 
procedures and activities of the Center and ICCVAM will be discussed at 
this meeting. NIEHS has invited knowledgeable individuals to 
participate in this meeting from a cross section of stakeholder 
organizations and institutions concerned with the development, 
validation, and use of alternative toxicological methods.
    Tenetative Agenda: The NIEHS and Interagency Staff will present the 
proposed procedures and activities of the Center and the ICCVAM; 
opportunities for public-private partnerships in the development, 
validation, and review of alternative methods; and the role of the 
Advisory Committee on Alternative Toxicological Methods.

8:45 a.m.  Welcome and Introduction
9:05 a.m.  Procedures and Activities of the Center and ICCVAM
11:45 a.m.  Public comment
12:00 p.m.  Lunch Break
1:00 p.m.  Partnership Opportunities
2:45 p.m.  Discussion on the Role of the Advisory Committee
3:30 p.m.  Public Comment
4:00 p.m.  Adjourn

    A description of the Center follows this announcement.
    Public Participation: The entire meeting will be open to the public 
with attendance limited only by space available. Members of the public 
who wish to present oral statements should contact Dr. Larry Hart below 
by telephone, fax, or mail as soon as possible, but no later than 
October 31, Speakers will be assigned on a first come, first serve 
basis, and will be limited to five minutes in length to allow for a 
maximum number of presentations. Written comments accompanying the oral 
statements are encouraged and should be submitted in advance if 
possible by mail or fax to Dr. Hart, NIEHS, P.O. Box 12233, MD: A3-07, 
Research Triangle Park, North Carolina 27709, telephone (919) 541-3971 
or FAX (919) 541-0295. Persons needing special assistance, such as sign 
language interpretation or other special accommodations should contact 
Dr. Hart as soon as possible.

FOR FURTHER INFORMATION CONTACT: Dr. William S. Stokes, Co-Chair, 
ICCVAM, Environmental Toxicology Program, P.O. Box 12233, NIEHS, 
Research Triangle Part, North Carolina 27709, telephone (919) 541-7997, 
FAX (919) 541-0947. The NIH Publication 97-3981, Validation and 
Regulatory Acceptance of Toxicological Test Methods, a Report of the ad 
hoc Interagency Coordinating Committee on the Validation of Alternative 
Methods, can be located on the internet at httpp://ntp-
server.niehs.nih.gov/htdocs/ICCVAM/ICCVAM.html, or a copy may be 
requested from the NTP Liaison Office, P.O. Box 12233, MD A3-01, 
Research Triangle Park, NC, 27709, Fax 919-541-0295, tel 919-541-0530, 
or email: [email protected].

    Attachment

    Dated: October 20, 1997.
Kenneth Olden,
Director, National Toxicology Program.

[Revised 10-15-97 \1\]
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    \1\ This proposal was originally discussed at an NIEHS/NTP 
Workshop on ``Developing Partnerships for the Validation of New 
Approaches for Toxicological Evaluation,'' held July 22, 1996 at the 
NIEHS, Research Triangle Park, NC.
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NTP Center for the Evaluation of Alternative Toxicological Methods

    Background/Need: Government, industry, and public interest 
groups have the responsibility to protect public health and the 
environment, and to prevent unnecessary exposure to hazards. In 
carrying out these responsibilities, scientists develop and adopt 
health and ecotoxicological testing methods to evaluate the 
potential adverse effects of chemicals or to demonstrate their 
safety. These methods are used to generate hazard identification and 
dose-response data to support health and environmental risk 
assessments for chemicals and products during their development, 
manufacture, distribution, use, and disposal.
    Toxicological testing methods are being developed and revised by 
the public and private sector with increasing frequency to provide 
for improved assessment of toxicity, to evaluate toxicity endpoints 
not previously assessed, to incorporate advances in biotechnology 
and out understanding of toxic mechanisms at the molecular and 
cellular level, to provide for improved efficiency (less time and 
expense), and to replace, reduce, and refine animal use. 
Requirements for the use of new test methods to generate information 
for regulatory purposes are twofold. First, the method must meet the 
criteria for validation, i.e., there must be scientific evidence 
that the method is reliable and relevant for its proposed use. 
Second, the method must meet the criteria for acceptance, e.g., 
there must be a determination that the use of the method will 
fulfill a specific need for one or more federal agencies. Until now, 
there has been no established process for federal agencies to 
coordinate the review of proposed methods with other federal 
agencies that may find the method useful.
    Participants at a recent National Toxicology Program (NTP) 
sponsored workshop \2\ and an ad hoc interagency committee \3\ 
recommended that an interagency coordinating committee be 
established whose functions would include the coordination of 
interagency reviews of toxicological test methods and communication 
with stakeholders throughout the process of test method

[[Page 55651]]

development and validation. The NIEHS, in collaboration with 13 
other federal agencies and programs, has recently established a 
standing committee that will carry out these functions. Designated 
as the Interagency Coordinating Committee on the Validation of 
Alternative Methods (ICCVAM), it is composed of representatives form 
the NTP Executive Committee agencies and several other federal 
regulatory and research agencies. The ICCVAM focuses on 
toxicological test method issues that are common to multiple 
agencies without impinging on considerations unique to individual 
programs and agencies. Final regulatory acceptance will be the 
purview of each Federal agency according to its regulatory mandates; 
however, the ICCVAM coordinated peer review should facilitate the 
acceptance decision process.
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    \2\ Final Report: National Toxicology Program Workshop on 
Validation and Regulatory Acceptance of Alternative Toxicological 
Test Methods,'' March, 1996, National Institute of Environmental 
Health Sciences, Research Triangle Park, NC, USA.
    \3\ 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 97-3981, 
March 1997. National Institute of Environmental Health Sciences, 
Research Triangle Park, NC. USA.
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    In order to implement the NTP workshop and ad hoc interagency 
committee recommendations, an NTP Center for the Evaluation of 
Alternative Toxicological Methods is being established to work with 
ICCVAM to carry out related activities. The Center includes the 
opportunity for public-private partnerships to enhance the level and 
scope of its activities. The Interagency Committee and Center 
initiatives implement Public Law 103-43 that directs NIEHS to 
develop a process to achieve regulatory acceptance of alternative 
test methods.
    Goal: The goal of the Center and ICCVAM is to promote the 
scieitnifc validation and regulatory acceptance of new test methods 
that are more predictive of human and ecological effects than 
currently available methods.
    Objective: To achieve this goal, the Center will collaborate 
with the ICCVAM to facilitate scientific peer review and interagency 
consideration of new test methods of multi-agency interest. Emphasis 
will be on methods with an appropriate biological basis for the 
species of concern that provide: improved toxicity characterization; 
savings in time and costs; and where possible, the refinement, 
reduction, and replacement of animal use.
    Regulatory Impact/Benefits: The expected benefits of this 
initiative include:
     Increased efficiency and effectiveness of test method 
review;
     Elimination of duplicative efforts across regulatory 
agencies;
     Utilization of shared expertise across the Federal 
system;
     Optimal utilization of scientific expertise outside the 
Federal government;
     Decreased total transaction costs and time to evaluate 
new and revised test methods;
     Elimination of redundant testing;
     Increased likelihood that new test methods will meet 
the needs of agencies; and
     Increased harmonization of testing requirements across 
the federal government and internationally.
    This program will benefit all parties by creating a forum to 
solicit expert input and provide communication during development, 
validation and review of proposed new test methods. Such methods, 
after acceptance by regulatory agencies, will provide for improved 
human health and ecological risk assessment and potential savings in 
time and costs. The program will also benefit animal welfare by the 
adoption of methods that refine, reduce, or replace the use of 
animals where scientifically feasible.
    Structure/Function: The overall structure encompasses the 
ICCVAM, a Center Office, Peer Review and Expert Panels, and a 
Federal Advisory Committee.
    The ICCVAM consists of representatives from federal regulatory 
and research agencies that generate or use information from 
toxicological test methods to support human health or environmental 
risk assessments. Members serve as points of contact and as sources 
to identify technical experts from their agencies to serve on 
specific topical workgroups. Committee activities may include the 
following, as appropriate:
     Evaluate the status of validation and make 
recommendations to agencies regarding the scientific usefulness of 
test methods and their potential applicability;
     Coordinate technical reviews of proposed new and 
revised test methods of interagency interest;
     Facilitate interagency communication and information 
sharing;
     Serve as an interagency resource and communication link 
with parties outside of the Federal government, including academic, 
other government, industry, and public interest groups;
     Assist agencies in assessing test method needs;
     Provide guidance to agencies and other stakeholders on 
criteria and processes for the development, validation and 
acceptance of tests;
     Promote awareness of accepted U.S. test methods; and
     Advocate harmonization of test methods nationally and 
internationally.
    The Center Office is located at NIEHS and consists of 3-5 
government professional and administrative staff augmented with 
appropriate contract support.\4\ The Center will collaborate with 
the ICCVAM to carry out activities to accomplish the following;
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    \4\ The project concept was peer reviewed and approved by the 
NTP Board of Scientific Counselors at their December 13, 1996 
meeting.
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     Communicate with interested stakeholders, and 
facilitate communication during the development and validation 
process with appropriate agencies; and
     Assess the completeness of submissions and determine if 
there are sufficient data for test methods to undergo independent 
public scientific peer review;
     Arrange for scientific peer reviews;
     Organize expert panels and/or workshops to assess the 
validation status of a method or group of methods;
     Provide recommendations and results to research and 
regulatory agencies;
     Prepare, publish, and distribute reports and 
information about new test methods.
    Peer Review Panels will be asked to develop scientific consensus 
on the usefulness of test methods to generate information for 
specific human health and/or ecological risk assessment purposes. 
They will discuss the biological relevance of the new test to the 
toxicity of interest. They will address how and when the new test 
method can partially or fully replace existing methods or 
approaches. When appropriate, panels will be asked to identify 
whether additional validation studies are necessary to adequately 
evaluate a method, and to identify additional research to support 
the development of mechanism-based test methods.
    It is anticipated that expert review panels will also be 
convened to evaluate the adequacy of current methods for assessing 
specific toxicities, to identify areas in need of improved or new 
methods, and to evaluate proposed validation studies. Agencies would 
use this information to establish priorities for appropriate 
research, development, and validation efforts in collaboration with 
interested parties.
    Products of the review process will be published reports that 
present a comprehensive peer review of the data substantiating the 
validity of a new method. The ICCVAM will forward recommendations 
regarding the scientific validity and potential acceptability of 
test methods to agencies for consideration. Each Federal agency will 
then, according to its regulatory mandates, determine the regulatory 
acceptability of a method.
    A Federal Advisory Committee on Alternative Toxicological 
Methods, composed of knowledgeable representatives from academia, 
industry, public interest/animal welfare organizations, federal and 
state government agencies, and the international community will 
review and provide advice on the activities and priorities of the 
Center, and advice on ways to foster partnership activities and 
interactions among all the stakeholders.
    Funding: Activities of the Center will be funded by a pooling of 
financial resources from interested partners, which may include 
federal agencies, industry, and other parties. NIEHS will provide 
core funding and professional and administrative staff for the 
Center. Other agencies will provide appropriate representatives and 
expert staff for the ICCVAM and its associated activities, including 
appropriate agency liaisons for peer review activities.
    Conflict of Interest Issues: Scientific peer review must be 
conducted by persons that are financially unencumbered with the 
outcome of the evaluation. All peer reviews will be required to 
comply with Federal government conflict of interest standards. 
Similarly, financial support of peer review activities must be free 
of any direct or apparent conflict of interest. To this end, funds 
to support Center activities will normally be deposited to the 
federal government and designated for the Center. NIEHS will 
disburse funds in accordance with federal regulations and 
guidelines.

[FR Doc. 97-28373 Filed 10-24-97; 8:45 am]
BILLING CODE 4140-01-M