In general, what they want (well, what your *price* constraints want!) is the least number of DIFFERENT hole sizes. Changing tools costs money (time). A board with 20 different hole sizes (gack!) is less efficiently manufacturable than one with *2* hole sizes.
That may have been the case some years ago where more than say 6 drills would cost you and I recall editing pads to get below this magic number. Recent quotes don't seem to take into account the number of drill sizes.
I can only assume that current CNC drilling technology can change drills-bits on the fly.
Number of hole sizes can be a good "advisory" to coax you into reexamining what you've done. (as can number of different components, component values, etc.).
Do you *really* need two different size mounting holes for the board? That means you've probably got two different fasteners in your BoM (not counting the things to which the fasteners attach!). Do your components REALLY have that many different lead diameters? Can't you make the smaller holes a wee bit larger?
Etc.
When I dismantle bits of kit, I make a note of just how much work it is for me to keep track of "what goes where"; are the screws different diameters? Lengths? Finishes? etc.
(If so, *why*? Couldn't they have PICKED one -- or two -- and accommodated all their needs with those?)
I suspect that they don't care how many sizes you use until you use more sizes than the tool changer of their drill can hold at one time. After you use more sizes than that (or after the total of sizes on a shared panel exceeds what the tool changer can hold) then they have to manually swap over tools (or maybe they just adjust your drill sizes for you!).
The place I use has all sizes of drill in 0.05mm increments.
They will 'make it so' within their stated tolerance. No extra charge for this. Don't expect tolerance closer than about 0.004-0.005" on drilled holes, but you can check their 'capabilities' list and see what they say.
Hint: 'tis usually better to be a bit on the large size than a bit on the small size, both in PCB holes and in hands.
Hint'': If you have square pins you can make it a bit tighter than with round pins because the swarf when you ram the pin in like a broach hath somewhere to go.
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