Test Method Validation and Regulatory Acceptance 2009: What’s in the Pipeline at JaCVAM

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In the Spotlight

Test Method Validation and Regulatory Acceptance 2009: What’s in the Pipeline at JaCVAM

Sherry Ward, Contributing Editor

Published: March 5, 2010

It’s been about a year since our article “Test Method Validation: What’s in the Pipeline in 2008” appeared as an In the Spotlight feature, so it’s time for an update!

The purpose of our 2008 article was to provide the AltTox community with a quick overview of new or revised toxicity test methods that were in some stage of assessment of their scientific validity for regulatory testing applications at each of the three major national validation centers, namely, the Japanese Center for the Validation of Alternative Methods (JaCVAM), European Centre for the Validation of Alternative Methods (ECVAM), and their US counterparts, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Toxicology Program Interagency Center on the Evaluation of Alternative Methods (NICEATM). This year, we are updating this information but will be covering the Japanese, European, and United States developments in turn, beginning here with Japan.

JaCVAM 2009

JaCVAM Director Dr. Hajime Kojima (who also serves as an AltTox Forum moderator) reports significant progress on JaCVAM’s participation in national and international validation studies in 2009. JaCVAM, created in 2005 as part of Japan’s National Institute of Health Sciences, already has effective methods in place for conducting validation studies, which are usually coordinated by the Japanese Society for Alternatives to Animal Experiments (JSAAE).

Other major activities of JaCVAM are similar to those of ECVAM and ICCVAM, and include conducting independent peer reviews, making recommendations to Japanese regulatory agencies, and participating in international test method validation and harmonization activities. JaCVAM groups established to coordinate these efforts include the following: JaCVAM Steering Committee, Validation Management Team, Peer Review Panel, and Regulatory Acceptance Board.

JaCVAM works closely with the JSAAE, which holds annual meetings where information on alternative methods and JaCVAM activities are communicated to relevant stakeholders. The 22nd Annual Meeting of the JSAAE, attended by over 300 scientists and policymakers, was held at Osaka University in November 2009. Dr. Kojima and other Japanese scientists also presented progress in the development and validation of alternative methods in Japan at the 7th World Congress on Alternatives in Rome in August-September 2009 in a number of oral and poster presentations.

Among JaCVAM’s many achievements in 2009 was the launch of the Center’s new website. An English version of the website was launched in August 2009. It provides information on JaCVAM and its activities. The committees and groups that participate in advising JaCVAM and in reviewing alternative methods in Japan are described. The Update on JaCVAM page provides a table that describes the validation, peer review, and regulatory acceptance status of alternative test methods that are undergoing or have undergone evaluation by JaCVAM.

JaCVAM continues to participate in international activities intended to facilitate the validation, acceptance, and/or harmonization of alternative test methods, including those of the Organisation for Economic Cooperation and Development (OECD), ECVAM, and ICCVAM. In 2009, Dr. Kojima participated as Japan’s representative in the signing of the International Cooperation on Alternative Test Methods (ICATM) agreement between Japan, the US, the EU, and Canada intended to enhance international cooperation on the validation and evaluation of new toxicity test methods.

JaCVAM and JSAAE scientists have provided important leadership in the dissemination of information on alternative methods to other Asian countries. In November 2009, Dr. Kojima participated in the 1st KoCVAM International Symposium and 6th Congress of the KSAAE, which introduced the new Korean Center for the Validation of Alternative Methods (KoCVAM).

The information provided in Table 1 is a summary of JaCVAM test method validation activities that were ongoing or completed in 2009. Table 2 summarizes the regulatory acceptance status of methods reviewed by JaCVAM.

Table 1. Toxicity test methods under assessment by JaCVAM in 2009.

Test MethodToxicity EndpointValidation Status
In vivo Comet AssayGenetic ToxicityOngoing international validation study in collaboration with NICEATM-ICCVAM and ECVAM; JaCVAM lead
In vitro Comet AssayGenetic ToxicityOngoing international validation study in collaboration with NICEATM-ICCVAM and ECVAM; JaCVAM lead
Cell Transformation Assay using Bhras cellsCarcinogenicityOngoing International validation study in collaboration with NICEATM-ICCVAM and ECVAM; JaCVAM lead
LUMI-CELL Estrogen Receptor Transcriptional Activation AssayReproductive Toxicity/ Endocrine DisruptorsOngoing international validation study in collaboration with NICEATM-ICCVAM and ECVAM
STTA Assay (antagonist)Reproductive Toxicity/ Endocrine DisruptorsOngoing international validation study in collaboration with Korean FDA; JaCVAM lead
h-CLAT using THP-1 cellsSkin Sensitization/ ImmunotoxicityOngoing international validation study in collaboration with ECVAM
3T3/ NRU assayAcute Oral SystemicToxicityJaCVAM Independent Peer Review ongoing
In vitro Pyrogenicity assaysPyrogenicityJaCVAM Independent Peer Review finished
rLLNASkin Sensitization/ ImmunotoxicityJaCVAM Independent Peer Review pending
LabCyte 3-dimensional Epidermal model (EPISKIN method using Japanese cell model)Skin IrritationOECD Independent Peer Review ongoing
EPIDERM and SkinEthic 3D skin modelsSkin IrritationJaCVAM Independent Peer Review pending
Cytotoxicity test of Short Time Exposure (STE) Assay using SIRC cellsEye IrritationIndependent Peer Review pending
Cytotoxicity test assay using SIRC cellsEye IrritationJaCVAM Independent Peer Review ongoing

Table 2. Regulatory acceptance status in 2009 of test methods endorsed by JaCVAM.

Test MethodToxicity EndpointValidation Status
LLNA-BrdUSkin Sensitization/ ImmunotoxicityJaCVAM Independent Peer Review completed; accepted by JaCVAM Regulatory Acceptance Board
EPISKINSkin IrritationJaCVAM Independent Peer Review completed; accepted by JaCVAM Regulatory Acceptance Board
Organotypic assays (BCOP, ICE) for severe to corrosive eye irritantsEye IrritationJaCVAM Independent Peer Review completed; accepted by JaCVAM Regulatory Acceptance Board; OECD Test Guidelines 437 and 438 adopted September 2009
Battery System: Yeast growth inhibition phototoxicity assay and red blood cell photohemolysis assayPhototoxicityJaCVAM Independent Peer Review completed; acceptance pending by JaCVAM Regulatory Acceptance Board

Sources of information for Tables 1 and 2
Kojima, H. (2009). JaCVAM Update. Powerpoint presentation at the June 2009 SACATM meeting. Available here.
JaCVAM website
Dr. Hajime Kojima, personal communication