I would suggest to move the game to the internal HDDs or SSD.
Origin and Steam have functions for that.
It also would be preferable to have the OS on the fastest drive you have, so on the SSD instead of a mechanical drive.
Okay after taking all my games off my SSD and putting Mass Effect on it seems to have fixed the issue. The bad thing is that single game takes up about half of my SSD. Is there a reason that this would happen only with my external?
Thanks to USB 3.0+ games installed on a external hard drives work most of the time, but external hard drives are not recommanded for games by Steam and that counts for any high performance software really.
Internal drives of the same performance class are just faster than external dives (Even if the difference is not that big anymore.) so there are still potential performance issues (like it seems to be the case here,) and they could disconnect in the wrong moment.
Furthermore, even if the MELE is a remaster many of the core functions are still functions of 10 years old games.
Is that why some of my games have problems such as Factorio when playing, the game will freeze for a few seconds whenever moving and for Assassin's Creed 2 the audio always sounds like it is clipping (both fixed by moving games to SSD)? I bought a 5tb WD Black cause I though I would be able to store my games and run them off of it but it seems like everything I play off of it has a problem.
I can't say that with absolute certainty, but it is likely.
I would suggest to get a additional internal HDD. Even a mechanical drive should not have this problem and they are really cheap by now. (But it should be a fast one, Serial ATA III 6,0 Gbit/s, 7200U/min)
With a additional internal SSD you should be on the save side no matter what.
Edit: And as said, it would be really better to have the OS on a SSD.
