I have an older USB 2.0 4 bay Drobo in RAID with a 2010 Mac Pro regular HD & 16gb ram. When I am running lots of Waves plugins it will crash. Sometimes. Depends on how many tracks, plugins and how much automation/events I have going. I think the RAID is part of the problem but I know if I got a SSD to replace my internal HD my system would be faster.
Short answer speed of your internal OS HD matters. If you get a good external with USB 3.0 or thunderbolt it will be fast enough.