CNC Milling Renshape for the first time ever..

We have just begun a huge project using Renshape material. I've never used this before but all the research I've done tells me to be ready for a mess. That's fine and we are ready to deal with that but I have some other concerns..

The job is mostly 3d milling which is no problem to program but holding the parts will get tough I think. There aren't many square edges to them so holding them in a vise for the most part won't be possible. My plan is to use helicoil inserts to hold the pieces down to a fixture plate so I can machine the 3d contours along the top of the part while also being able to mill the outside shape in the same process. The parts range from 4x4x6 to 36x18x6 so some would require more construction holes than others of course. I've used helicoils to hold down plastic many times with success but being that I have never used this material before I'm worried that they will just pull right out and leave me in a pickle. I also am not sure if I can get away with using a 4 flute end mill to do my rough milling with. Any thoughts on tooling + workholding would be greatly appreciated. Thanks.

Been a long time since I've cut the stuff, so I can't remember feeds and speeds, but I can remember some stuff. This is for the grey version, don't remember the specific brand/series:
Helicoils worked well.
We used 4 flute cutters and our standard general purpose face mills, but that was more what we had on hand and less the ideal cutters. It cut just fine, but these were one-offs and we weren't trying to make time.
The stuff is messy as hell. If the machine runs coolant normally, make sure you thoroughly clean the machine before and after running the material. We did a complete wipe down with simple green. It turns to a nasty sludge otherwise.
Respirators or an enclosure are required. It's super nasty to breathe in. Also has a heavy sulfur smell.
We used it for fixtures, and I remember sealing it with one light coat of spray can clear coat when we were done to help keep it clean long term. May not apply to your application.

Sounds like a vacuum plate and couple of locator pins would do the job.

We machine tooling board at work from time to time. We usually just square it up and hold it in a vise...usually 14x10x3 or somewhere around there. There's not much tool pressure involved with cutting. Sharp 2 and 4 flute cutters will do.