[Federal Register Volume 71, Number 18 (Friday, January 27, 2006)]
[Notices]
[Pages 4603-4604]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-1019]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


National Toxicology Program (NTP), NTP Interagency Center for the 
Evaluation of Alternative Toxicological Methods (NICEATM); Nomination 
To Hold a Workshop on Alternative Methods To Replace the Mouse 
LD50 Assay for Botulinum Toxin Potency Testing: Request for 
Comments, Nominations of Experts, and Submission of In Vivo and In 
Vitro Data

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.

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SUMMARY: In October 2005, the Humane Society of the United States 
(HSUS) submitted a nomination to NICEATM requesting that alternative 
test methods to the mouse LD50 assay for botulinum toxin 
potency testing be assessed and prioritized for prevalidation and 
validation efforts. The nomination proposed that an initial key step in 
this process would be for the Interagency Coordinating Committee on the 
Validation of Alternative Methods (ICCVAM) to organize a workshop on 
this topic. ICCVAM considered the nomination and supports with a high 
priority the concept of a workshop to discuss alternative methods and 
approaches that might reduce, refine, or replace the use of animals for 
botulinum potency testing. The Scientific Advisory Committee on 
Alternative Toxicological Methods (SACATM) considered the nomination 
and the ICCVAM proposal at its meeting on December 12, 2005, and agreed 
that the proposed activity should have a high priority. At this time, 
NICEATM requests (1) information on development and/or validation 
activities relevant to reduction, refinement (less pain and distress), 
and/or replacement alternatives for botulinum toxin potency testing, 
(2) public comments on the appropriateness and relative priority of 
proceeding with a workshop on this topic, (3) the nomination of 
scientific experts who might participate if a workshop occurs, and (4) 
the submission of data from mouse LD50 botulinum potency 
testing and ex vivo and in vitro test methods used for botulinum toxin 
potency testing. The HSUS nomination is available at http://iccvam.niehs.nih.gov/ see ``Nominations and Submissions.''

DATES: Comments, nominations of expert scientists, and data submissions 
should be received by March 13, 2006.

ADDRESSES: Correspondence should be sent by mail, fax, or e-mail to Dr. 
William S. Stokes, NICEATM Director, 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].

SUPPLEMENTARY INFORMATION:

Background

    In October 2005, the HSUS submitted a nomination to NICEATM to 
organize a workshop to evaluate the state-of-the-science for potential 
alternatives to the mouse LD50 assay for botulinum toxin 
potency testing. The HSUS nomination is available at http://iccvam.niehs.nih.gov/ see ``Nominations and Submissions.'' ICCVAM 
considered the nomination and supports the concept of a workshop to 
discuss alternative methods and approaches that might reduce, refine, 
or replace the use of animals for botulinum potency testing with a high 
priority. The SACATM discussed this nomination at its meeting on 
December 12, 2005, and advised NICEATM and ICCVAM that they consider 
the development and validation of alternatives to the mouse 
LD50 assay for botulinum toxin potency testing a high 
priority. SACATM also suggested that prior to convening a workshop that 
ICCVAM and NICEATM find out what efforts toward developing or 
validating alternatives might already be underway by companies that 
conduct botulinum potency testing. NICEATM now seeks (1) information on 
any activities directed at the development and/or validation of 
alternatives to the mouse LD50 assay for botulinum toxin 
potency testing, (2) input from the public on this nomination for a 
workshop, (3) the nomination of scientific experts who might 
participate in any future workshop on this topic should it occur, as 
well as (4) data from mouse LD50 botulinum potency testing 
and ex vivo and in vitro test methods used for botulinum toxin potency 
testing. NICEATM and ICCVAM will consider this information and 
determine how to best move forward with this nomination.

Request for Comments, Nominations of Scientific Experts and Request for 
Data

    NICEATM requests information on the status of any efforts to 
develop alternatives to the mouse LD50 assay for botulinum 
toxin potency testing, as well as public comments on the 
appropriateness and relative priority of the proposed workshop 
activity. In addition, NICEATM requests the nomination of scientists 
with relevant knowledge and experience to potentially participate in 
the workshop should it be held. Areas of relevant expertise include, 
but are not limited to: neurophysiology, neuropharmacology, 
neurotoxicity, immunology, potency testing of toxins and other 
biologicals in animals and in vitro systems, development and use of in 
vitro methodologies, and biostatistical data analysis. 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.
    NICEATM invites the submission of data from in vivo botulinum toxin 
potency testing, including clinical observations and corresponding 
time-course information, and information and data from ex vivo and in 
vitro test methods being used as potential alternatives to the mouse 
assay for botulinum toxin potency testing. Submitted data will be used 
to further evaluate the usefulness and limitations of in vitro potency 
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 alternative test 
methods for assessing potency of botulinum toxin.
    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

[[Page 4604]]

notebooks and/or study reports, if available. Raw data and analyses 
available in electronic format may also be submitted. Each submission 
should preferably include the following information, as appropriate:
     Specific type of botulinum neurotoxin tested (e.g., 
Clostridium botulinum neurotoxin type A)
     In vivo potency test protocol used.
     In vivo potency test results.
     Individual animal responses, including time of onset of 
specific clinical signs and death.
     Alternative ex vivo or in vitro test protocol used.
     Alternative ex vivo or in vitro test results.
     The extent to which the study complied with national or 
international Good Laboratory Practice (GLP) guidelines.
     Date of the study.
     The organization that conducted the study.
    Although public comments and data can be accepted at any time, 
information submitted by the deadline listed in this notice would be 
most useful for determining whether a workshop is the appropriate next 
step in pursuing an alternative to the mouse LD50 assay for 
botulinum toxin potency testing. In addition, submitting information by 
this date ensures its availability to workshop participants if a 
workshop is held.

Background Information on ICCVAM, NICEATM, and SACATM

    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) 
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.
    The SACATM, established January 9, 2002, is a federally chartered 
advisory committee composed of scientists from the public and private 
sectors (Federal Register: March 13, 2002: Vol. 67, No. 49, page 
11358). The SACATM provides advice to the Director of the NIEHS, 
ICCVAM, and NICEATM regarding statutorily mandated duties of ICCVAM and 
activities of NICEATM. Additional information about SACATM, including 
the charter, roster, and records of past meetings, can be found at 
http://ntp.niehs.nih.gov/, see ``Advisory Board & Committees.''

    Dated: January 17, 2006.
Samuel H. Wilson,
Deputy Director, National Institute of Environmental Health Sciences.
 [FR Doc. E6-1019 Filed 1-26-06; 8:45 am]
BILLING CODE 4140-01-P