The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.
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TestSmart HPV
April 26-27, 1999
Hyatt Fair Lakes
12777 Fair Lakes Circle
Fairfax, VA 22033
A workshop of The Johns Hopkins Center for Alternatives to Animal Testing
TestSmart is a program of the Vision 20/20 forum
This workshop is partially funded through a grant by the Vira I. Heinz Endowment
Abstract for TestSmart--A Humane and Efficient Approach to Screening Information Data Sets (SIDS) Data
High Throughput Screening Assays
Neil Wilcox
Food and Drug Administration
The Vision 20/20 Workshop, TestSmart: A Humane and Efficient Approach to SIDS Data, April 26-27, 1999, included a session entitled, "High Throughput Screening Assays." A broad array of developing technologies were presented which provided an excellent overview of practical and novel applications in hazard testing. Six speakers were charged with providing 30 minute overviews that included background on their technologies, current applications, targeted endpoints, and their relevance to safety testing and the Organization for Economic Cooperation and Development (OECD) Screening Information Data Sets (SIDS) database; finally, they were asked to present their vision for these technologies in the future with special emphasis on product development and potential for meeting regulatory requirements.
In the broadest sense, the high throughput screening (HTS) assays presented included genomics, proteomics, non-invasive imaging, transgenic models, in vitro methods, microarray technology, analysis by structure activity relationships (SAR) including combinatorial synthesis, and data mining for predictive modeling. Advantages illustrative of these approaches included the ability for rapid screening for toxicology, small sample size, small reagent volume, large sample numbers conducted simultaneously, robotics, real time analysis, and the genesis for large databases.
Clearly, the potential benefits from these technologies are many and remain largely untapped. In summary, the benefits of the HTS technologies discussed in this session included, but were not limited to, the following:
- Measure multicellular events simultaneously.
- Provide gene expression with potential to identify mechanisms of toxicity.
- Predict drug interactions without animal testing.
- Enlist non-invasive imaging that tracks, spatially and temporally, biological events in vivo.
- Facilitate drug discovery and development.
- Identify gene regulation, gene expression, and resulting toxicity.
- Provide cell-based assays in a physiological environment.
- Measure and cross-correlate multiple parameters within same cell.
- Analyze specific cell sub-populations or cell types within mixed populations.
- Allow more efficient use of animal tissue.
It was apparent that currently developing HTS technologies have the potential to impact the regulatory community by improving the accuracy and speed of predicting toxicity to xenobiotics while reducing, refining, and replacing animal use in testing. Moreover, it was emphasized that there would be certain expectations; viz., every model system has its limitations as surrogate predictors. Additionally, it is important to understand that, from the regulatory perspective, there is a hierarchy of toxicity study questions; e.g., current thinking is to integrate the HTS methods early in the development process of regulated products, therefore, rendering their data supportive rather than definitive.
In conclusion, it was recommended that a series of workshops be considered to address issues related to HTS technologies. There are multiple scientific disciplines and approaches incorporated in genomics, proteomics, and all other applications represented within the broad purview of high throughput technology. It would be beneficial, for example, to establish a rubric to categorize methods according to the endpoints they characterize or any other metric relevant to the target species. Similarly, new terminologies are emerging within the HTS arena and requiring a dedicated nomenclature necessary to foster international harmonization. Finally, the current status of these technologies needs to be placed in perspective to explore potential for test batteries and, in general, to interpret the meaning of new data.
Many thanks to Dr. Alan Goldberg, Director, Johns Hopkins Center for Alternatives to Animal Testing (CAAT), and his staff for the excellent organization of the TestSmart workshop. Furthermore, special recognition and appreciation are extended to the HTS guest speakers and their supporting organizations for their time, expertise, and commitment to explore new technology in SIDS testing for the High Production Volume (HPV) initiative.