Ideally, the undiluted product should be screened as long as there is no interfering/enhancing property within the LAL test. However, in some product formulations, the ingredients interfere with the LAL test. For such formulations, the USP recommends that the product be diluted to overcome interference or enhancement properties. The calculated MVD is the dilution of a sample at which the endotoxins limit would be detected, but it should not be the regular testing dilution. When product interference is encountered during development, FDA recommends that the firm determine the lowest product dilution that would neutralize the interfering condition.
FDA recommends that firms begin subsequent product screening at a product dilution just above the level that neutralized the interference. For example, if the product has an MVD of 1:100, and the product displays inhibition at the 1:10, but not at the 1:20, it may be best to screen product at 1:30. If bacterial endotoxins are detected at this level, then the firm should conduct full enumeration with the product to titrate the true amount of endotoxins.
