We use Dynastrip Imposition Software so there is no need for 2-up or 4-up layouts. One PDF with all the pages in order, in CMYK color (NOT RGB) with all fonts and images embedded at a minimum 300 dpi resolution.
Allow 25-30% dot gain. Type in 2 colors or more AND type reversing out of a color CAN NOT be less than 13pt. Black type should be 100% black (No Cyan, Magenta, or Yellow).