Most technical divers use a primary regulator with a long hose so that it may easily be donated to another diver in an emergency. Use of a custom regulator mouthpiece in that situation may have an issue. That's because the other diver might have difficulty using the regulator with someone else's custom mouthpiece. If you choose to use a custom mouthpiece on a long hose configuration, make sure to check with your teammates to be sure they can accept the mouthpiece.
There are no issues on traditional recreational 'octopus' regulator configurations where the primary is never donated. There also would be no issues with using a custom mouthpiece on deco regulators, which may actually be in the mouth for much more time than the primary. Further, there are no issues with rebreather loops using a custom mouthpiece (if it fits the DSV) because they are never donated.
The custom mouthpieces offer the absolute best comfort, but may not always be appropriate. For a very comfortable one-size-fits-all type mouthpiece, take a look at the C-Bite Mouthpiece.