I was near-apoplectic with fear before I handed my pages over to Oni Press. I was sure they were going to tell me off for my unflatted pages. All I have ever done is scan my linework at 600dpi in black and white, converted to RGB, coloured white bits between the lines with the paint bucket, converted to CMYK, and prayed. (Sometimes I didn't even pray.)
(My apologies to the artist in question, who I am not singling out for criticism. Quite the opposite - he/she is plainly a brave soul)
On my older books, just the act of converting to CMYK turned the RGB black into a very rich CMYK - too rich really. But I got away with it. Before I sent my art to Oni, I tried to find out what the correct rich black ratio was. I figured that was the only way I might get away with not having to painstakingly recolour hundreds of pages.
MY PROVEN SYSTEM/ONE WEIRD TIP:
If your line art is solid black (ie scanned at a high resolution and not anti-aliased), colour the page any way you want, then convert to CMYK if the page isn't CMYK already, select all the black linework at the end and fill it with a 60C/40M/0Y/100K black. That's it. I've done this for multiple major comic book publishers, as well as on my own self-published work, and it is apparently wholly acceptable in preventing trapping errors (white hairline gaps around the lines when pages aren't properly registered).
NOTE: Don't colour your lettering this way. Keep it 0C/0M/0Y/100K or it will look slightly fuzzy on the page.