View document: Recommended Performance Standards: Murine Local Lymph Node Assay
[PDF]
Overview
The LLNA was the first alternative test method evaluated and recommended by
ICCVAM. Based on the recommendations of ICCVAM and an independent scientific review panel, the
LLNA has been accepted by U.S. and international regulatory authorities
as a stand-alone test method for assessing the potential
of a substance to induce allergic contact dermatitis.
ICCVAM currently routinely develops performance standards for test methods. Before
a new test method is accepted for regulatory testing applications, validation studies are
conducted to assess its reliability (i.e., the extent of intra- and inter-laboratory reproducibility),
and its relevance (i.e., the ability of the test method to correctly predict or measure the biological
effect of interest, which is partly dependent on the accuracy of the test method). Performance
standards communicate the basis by which new proprietary (i.e., copyrighted, trademarked, registered)
and nonproprietary test methods have been determined to have sufficient accuracy and reliability for
a specific testing purpose. These performance standards can then be used to evaluate the accuracy and
reliability of other proposed test methods that are considered functionally and mechanistically similar
to the accepted test method.
|
|
When ICCVAM evaluated the LLNA in 1999, the concept of performance standards had not been
developed. ICCVAM subsequently defined performance standards and described a process for their
development (ICCVAM 2003). In 2007, the U.S. Consumer Product Safety Commission (CPSC) asked ICCVAM
and NICEATM to evaluate the scientific validity of non-radioactive versions of the LLNA that could
be used in place of the traditional LLNA, which measures the incorporation of radioactivity
(3H-thymidine) in the draining auricular lymph nodes. ICCVAM decided at that time to develop
performance standards that could be used to more rapidly and efficiently determine the validity of
these and other modified versions of the LLNA.
The European Centre for the Validation of Alternative Methods (ECVAM) also independently drafted
LLNA performance standards in 2007, and the Japanese Center for the Validation of Alternative
Methods (JaCVAM) initiated two validation studies of modified LLNA test methods using a list of
proposed reference substances to evaluate their validity. With an obvious international interest in
developing LLNA performance standards, ICCVAM, JaCVAM, and ECVAM agreed to work together to develop
internationally-harmonized LLNA performance standards.
ICCVAM has developed recommended performance standards for the LLNA and will publish them in 2009. These
performance standards reflect extensive discussions that took place between ICCVAM, ECVAM, and
JaCVAM during 2007 and 2008, and represent a set of internationally-harmonized standards for the
conduct of the LLNA.
View Federal Register notice announcing availability of initial draft of performance standards
(Vol. 72, No. 176, pages 52130-52131, September 12, 2007) [PDF]
View Public Comments Submitted in response to FR Notice
|