We caught this because spot colors used in EPS files and passed through ghostscript work as expected. Using direct-to-pdf, the same print job had elements vanish from the printed product.

Problem –
EPS files created in Illustrator using layers and spot colors without transparency are rendering incorrectly in print. The layers are not knocking out the layer below it but allowing the next EPS layer to been seen, as in overlaying on top of the previous layer. This can be previewed in the PDF by going into Acrobat, Print Production tool, output preview and having the simulate overprinting option check on. This is the default we have been working with prior to direct-to-pdf. This was not an issue for our documents with ghostscript to PDF.
PDFPDF
Settings in place –
XPP color specs have spot colors defined, illustrator has spot colors defined in the EPS files. Upon printing those EPS colors and layers should pass through to the printer and print as a composite image. We are on XPP 9.4.

Things we have tried –
-Setting white to overprint in the color spec solves the issue for white disappearing, but not for the other spot colors in the EPS file
-Importing EPS colors into color spec using EPSF color importer … but this doesn’t seem normal. We didn’t have to do it before and doesn’t make practical sense to create a new color spec for every batch of new EPS files.
-Converting spot colors in EPS files to process works, but we need to spot colors and spot color names to pass through to the printers for print accuracy and color matching with the web PDF.