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High Throughput Pre-Screen Demo/Validation
1. Develop a list of "preferred assay scheme characteristics" that would be stated in a request for proposal to firms submitting proposals to perform the HTPS program. These characteristics include: the ability to bind to estrogen alpha, estrogen beta, androgen, and thyroid; incorporating plus/minus etabolism; including reporter gene product (agonist and antagonist); preparation and processing of the chemicals; and incorporating relative potency E-C50. The proposal would have to specify identify the assays that would be used in the HTPS by name, cell type, conditions (e.g., with/without metabolic activation etc.), and state or reference the protocol to be followed.
2. Select the compounds to be used in the demo/validation program. The purpose of this program is to determine if the assays developed for use in the pharmaceutical industry are useful for screening pesticides, commercial chemicals, and contaminants. The challenge of the non-pharmaceutical application is that a much wider range of structural and physical and chemical properties will be encountered. In addition, we are more concerned about assay sensitivity than the pharmaceutical industry since we will be interested in detecting compounds with low potency (the pharmaceutical industry is only concerned with identifying highly active compounds). Thus, known positives, known negatives and a wide variety of chemicals need to be tested in the demo program.
3. Obtain a laboratory to conduct the demo/validation program. Several options exist for obtaining a lab:
- Option A: EPA could procure a laboratory in about 60 days time by using a small purchase agreement. This involves a quick turnaround competitive bidding process and the evaluation of submitted proposals. The cost limits on this procurement mechanism is $100K.
- Option B: Use the ICVAM/NTP contract for validation of studies. The status of this contract could not be verified at the time of writing. My understanding is that it is designed to carry out standardization and validation of protocols.
- Option C: Have CMA contract with a laboratory to conduct the pilot. A steering committee composed of industry, EPA and environmental group representatives would provide technical direction and oversight to the contractor.
Obtain and deliver the chemicals to be tested to the laboratory. There are several options to providing chemicals for purposes of this demo/pilot.
- Option A: Purchase chemicals from a specialty chemical supplier.
- Option B: Obtain chemicals from industry.
Provide technical oversight to contractor. A panel of composed of EPA, industry, and environmental group experts would provide technical direction to the contractor.
Obtain and analyze the data. EPA or the group that provided technical direction could analyze the performance of the assays.