ME5 doesn't "have" to do anything with plot holes from the previous series. ME (1-3) settled the story of Shepard and the Reapers (whether or not you like the ending, it's over), the only thing the next ME NEEDS to do is tell a compelling story with compelling characters with the ME universe and lore as it's backdrop. Something Andromeda failed miserably at. I'd be perfectly ok (happy even) if they ignored or set aside for later, anything that occurred or had to do with Andromeda. Bioware and the people that worked there tried hard to bring something different/new to continue the series but fact is they shot their shot and missed. It wasn't an ME game really, it was a story that had only 1 level, colonialism of a basically empty different galaxy, with only 1 species (the Angara) who knew nothing about the mass effect and it's technology, and having it invaded by two different entities from other galaxies (the Kett, and the milky way species) one through military conquest and the other through "supposedly" friendly means (you could argue that the milky way species were just as bad as the Kett ignoring the sovereignty of the Angara by rapidly spreading throughout their galaxy like roaches. It was terrible.