Screening test development, technical

The technical points that follow exemplify the test performance information that should be available for all screening tests. The technical items are not intended as evaluation criteria since the evaluation of the performance of any specific test depends on the public health or regulatory significance of the test results and the ultimate use of the results. The technical points are intended to suggest to test developers the type of information that should be available for their products. 

There are many alternative in vivo mammalian and non-mammalian and in vitro test assays. But at present no alternative test can totally replace the existing reproductive toxicity tests using live mammalian animals (ECETOC 1989). In many instances, however, the alternative methods can be used to screen test compounds of known or unknown efficacy for further technical development or further testing. 

Free or unbound cortisol represents the biologically active form of the circulating hormone, and its concentration is practically independent of alterations of its transport proteins. Various methods have been developed for estimating the free fraction in serum, but these assays are technically demanding, expensive, and not in general use. The measurement of urine free cortisol comes closest to providing an estimate of the free hormone concentration. As mentioned previously, approximately 2% of cortisol is excreted into the urine in a free form, and its measurement has been shown to be of use as a screening test for cortisol hypersecretion. However, P-hydroxycortisol has been reported to interfere with the immunoassay of free cortisol in urine. ... 

Whereas the in vitro tests for APD prolongation and Ikr blockade have advanced the ability to screen for QT prolongation, there are a number of technical limitations, and the results do not necessarily correlate with occurrence of adverse cardiac effects in patients. Therefore, these tests are regarded as a means of identifying the presence of a potential risk. Results of all in vitro and in uivo cardiovascular tests must be considered and integrated in developing a complete risk assessment (106). 

CTS and PTS screen experimental products, test and evaluate them for end-use significance, and conduct field development and technical service for those products which promise success. 

B. Phase 2 Development The Development Representative will ensure the screening of product candidates. External evaluation by selected customers (technical partners) may be initiated to obtain early performance feedback, especially in areas where the company is unable to perform the key tests necessary, or to obtain early vahdation of company test results. In Phase 2 there is no commitment to commercialization. The Director of Marketing of the Business Unit responsible for the experimental product area must approve in writing sampling an R D substance outside of the company and shall ensure compliance with Procedure Number Lab. 5, Sampling R D Substances to Third-Parties. If sampling is to a destination outside of the United States, the Director of Marketing shall inform the MRC who shall determine if the substance is subject to the export notification requirements ofTSCA 12(b). 

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