[Federal Register Volume 64, Number 231 (Thursday, December 2, 1999)]
[Notices]
[Pages 67579-67580]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-31342]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


National Institute of Environmental Health Sciences National 
Toxicology Program; Availability and Request for Comments on the 
Revised Guidance Document: Evaluation of the Validation Status of 
Toxicological Methods: General Guidelines for Submissions to the 
Interagency Coordinating Committee on the Validation of Alternative 
Methods (ICCVAM)

Summary

    The Interagency Coordinating Committee on the Validation of 
Alternative Methods (ICCVAM) prepared an initial version of the 
document, Evaluation of the Validation Status of Toxicological Methods: 
General Guidelines for Submissions to the Interagency Coordinating 
Committee on the Validation of Alternative Method in May 1998. It has 
now been updated by ICCVAM to reflect experience gained with the first 
two test methods reviewed by ICCVAM in 1998-1999. Further modifications 
are anticipated as experience accrues. The document provides guidance 
to test method developers on the information needed by ICCVAM to 
evaluate the validation status of new or revised test methods at any 
stage of development and after the completion of validation studies. It 
includes a framework for organizing the information supporting the 
validity of a test method. The purpose of this notice is to announce 
the availability of the revised guidance document and to request 
comments and suggestions for further improvement.

Background

    The Interagency Coordinating Committee on the Validation of 
Alternative Methods (ICCVAM) was established in 1997 as a standing 
collaborative effort by the National Institute of Environmental Health 
Sciences (NIEHS) and 13 other regulatory and research agencies. ICCVAM 
coordinates issues within the Federal government that relate to the 
development, validation, acceptance, and national/international 
harmonization of toxicological test methods. The Committee's functions 
include the coordination of interagency scientific reviews of 
toxicological test methods and communication with outside groups 
throughout the process. The focus is on new and revised test methods 
that are applicable to multiple Federal agencies. Emphasis is given to 
test methods that provide for improved prediction of adverse human 
health or ecological effects, and that may reduce, refine, or replace 
animal use.
    In the report, Validation and Regulatory Acceptance of 
Toxicological Test Methods: A Report of the ad hoc Interagency 
Coordinating Committee on the Validation of Alternative Methods (http:/
/ntp-server.niehs.nih.gov/htdocs/ICCVAM/iccvam.html), various stages 
were identified to move a proposed test method from concept to 
regulatory acceptance. One stage is the communication of a proposed 
test method by the sponsor to ICCVAM for consideration and review. The 
ICCVAM review process typically involves an assessment by an ICCVAM 
working group comprised of government scientists, followed by an 
independent peer review evaluation by an expert scientific panel. 
Following this review, ICCVAM forwards recommendations on the 
usefulness and limitations of the proposed test method to regulatory 
agencies. Based on their specific regulatory mandates, each Federal 
agency then makes a determination regarding the acceptability of the 
test method. If the test method is accepted, appropriate actions (e.g., 
revision of existing regulations, guidelines, and/or guidance 
documents) are taken to inform the regulated community.
    The following Federal regulatory and research agencies participate 
in this effort:

Consumer Product Safety Commission

[[Page 67580]]

Department of Defense
Department of Energy
Department of Health and Human Services
    Agency for Toxic Substances and Disease Registry
    Food and Drug Administration
    National Cancer Institute
    National Institute for Occupational Safety and Health/Centers for 
Disease Control
    National Institute of Environmental Health Sciences
    National Institutes of Health
    National Library of Medicine
Department of the Interior
Department of Labor
    Occupational Safety and Health Administration
Department of Transportation
    Research and Special Programs Administration
Environmental Protection Agency

    To support the activities of ICCVAM, NIEHS established the National 
Toxicology Program Interagency Center for the Evaluation of Alternative 
Toxicological Methods (NICEATM). NICEATM provides a means of 
communication between test developers and Federal agencies during the 
development and validation process. NICEATM coordinates test method 
workshops, expert panel meetings, and independent scientific peer 
reviews, where appropriate and recommended by ICCVAM. Test method 
developers are encouraged to contact NICEATM
(http://iccvam.niehs.nih.gov) prior to submission of proposed test 
methods for guidance on the submission and evaluation process.
    Before a new or revised test method is used to generate information 
to support regulatory decisions, it must be: (a) Validated to determine 
its reliability and relevance for its proposed use and (b) determined 
to be acceptable by one or more regulatory agencies to fill a specific 
need. Criteria for validation and regulatory acceptance have been 
prepared and are described in the report, Validation and Regulatory 
Acceptance of Toxicological Test Methods: A Report of the ad hoc 
Interagency Coordinating Committee on the Validation of Alternative 
Methods (http://ntp-server.niehs.nih.gov/htdocs/ICCVAM/iccvam.html). 
Prior to the initiation of any test method development or validation 
efforts, sponsors are encouraged to consider the validation and 
acceptance criteria described in the report.
    ICCVAM is issuing revised guidance for developers on organizing 
information needed to assess the validation status of a new or revised 
test method at any stage of development and/or following the completion 
of validation studies. The guidance document, Evaluation of the 
Validation Status of Toxicological Methods: General Guidelines for 
Submissions to ICCVAM, is available online (http://
iccvam.niehs.nih.gov/doc1.htm); additional copies can be obtained from 
the National Toxicology Program (NTP) Interagency Center for the 
Evaluation of Alternative Toxicological Methods (NICEATM, contact 
information given below). The initial guidance document was first 
released in May of 1998. This version has been updated by ICCVAM to 
reflect experience gained with the first two test methods reviewed by 
ICCVAM in 1998-1999: the Local Lymph Node Assay (http://
iccvam.niehs.nih.gov/llnarep.htm) and Corrositex (http://
iccvam.niehs.nih.gov/corprrep.htm).
    The guidance document calls for the development of an ICCVAM 
submission for a given test method that describes the extent to which 
the validation and acceptance criteria have been addressed. It can also 
be used as a guide to prepare background review documents for methods 
that describe how validation criteria will be addressed in proposed 
studies. Background review documents serve as comprehensive 
compilations of all existing data for test methods. Completion of 
background review documents prior to the conduct of validation studies 
is encouraged to provide the basis for decisions on standardized 
protocols and design of the validation studies. In preparing test 
method submissions and background review documents, developers should 
use the outline provided to organize information. Submissions should be 
prepared well in advance of any peer review of the validation status of 
a method.
    Test method developers are encouraged to consult with NICEATM and 
ICCVAM during submission preparation and throughout test method 
development, pre-validation, and validation. The objective of these 
interactions is to maximize the likelihood that adequate information 
will be generated to characterize the usefulness and limitations of a 
test method. If requested, ICCVAM will solicit interagency comments on 
proposed study designs and protocols. Validation study designs 
submitted to ICCVAM for comment should describe the basis for the 
proposed protocol and proposed validation studies. The completed 
submission is then used to assess the method's validation status 
through an independent ICCVAM peer review process. This process 
enhances the likelihood that agencies will be provided with sufficient 
information to determine a method's usefulness and limitations for 
meeting regulatory needs.

Request for Comments

    Interested parties are encouraged to submit comments on the ICCVAM 
guidance document: Evaluation of the Validation Status of Toxicological 
Methods: General Guidelines for Submissions to ICCVAM. Comments should 
include name, affiliation, mailing address, phone, fax, e-mail and 
sponsoring organization (if any). Comments may be submitted anytime; 
however, those received within 60 days from the appearance of this 
notice will be considered by ICCVAM for a possible revision in early 
2000. The document is available on the Internet at http://
iccvam.niehs.nih.gov/doc1.htm or may be requested from NICEATM, MD-EC-
17, P.O. Box 12233, Research Triangle Park, NC 27709; 919-541-3398 
(phone); 919-541-0947 (FAX); and [email protected] (e-mail). 
Comments should be directed to the ICCVAM Co-Chairs, Dr. William S. 
Stokes 919-541-7997 (phone); 919-541-0947 (fax); [email protected] 
(e-mail) or Dr. Richard Hill 202-260-2894 (phone); 202-260-1847 (fax); 
Hill.R[email protected].

    Dated: November 24, 1999.
Samuel H. Wilson,
Deputy Director, NIEHS and NTP.
[FR Doc. 99-31342 Filed 12-1-99; 8:45 am]
BILLING CODE 4140-01-P