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The two designs would need to be the same number of layers (and dielectric thicknesses per layer, if you are specing that out.) Also, you'll be paying the cost of whichever board has the smallest feature sizes across both. If you are already doing N-up on a panel, the fab house might be able to combine them for you. Or else do it yourself in the cad tools, by either panelizing them yourself, or putting a good score/breakaway/board notch/etc. between the two.
I always liase with my fab houses on what they can get out of a standard panel, I quite often use a panel of 219mm x 296mm as all of my PCB fabricators can get two of these panels out of one standard sheet (size as quoted above). This size also fits 95% of all boards we design, allowing to get 3 to 6 boards on a panel and still have room for our in house assembly requirements. These are things such as a border to allow for conveyors, global location holes for de-panelisation etc.
I design all my PCBs within the panel when desigining a board, such that the board design is a sub of the overall panel (as it is the panel that is going to pass through production). The panel details are on various layers within my CAD package, thus when I finish the design I post process the panel data (datums, fids etc) as well as the board design. Read the ODB++ (or Gerbers if you are old fashioned ) step the board design and voila send the data of for PCB fabrication and solder paste screen.
Oh I also always design with certain datums in fixed locations such as the master fiducial, then I can use script files and macro to automaticaly re-create required data such as pick and place files (I always generate a root image pick and place file with a fiducial at 0,0).