storage expansion

You can go to 12TB drives in a 4220 with no issues.  You won't get 144TB in RAID, but you'll get more than you have now (you'll get 109TiB).  If there is a real limit to what OS6 can handle, Netgear has not disclosed it.  Based on BTRFS limitations, it's far past what 3.5" drives will likely ever attain.  The max size limits you see in Netgear specs are based on the largest drives available at the time of release.  So on a 4220, that's a few years ago.

But, replacing each of 12 drives one at a time and wating for re-sync is going to take an eternity as well as put a lot of stress on the drives.  If you really need to replace them all, you are much better off replacing all the drives and re-creating the volume from scratch, then restoring configuration from a saved one and files from backup.  Replacing only as many as you need for current demand is a better plan, then doing more as the need changes.  If you want to replace all drives because they are getting older (in which case, all that stress of resync could push one or more over the edge), you can also re-create it with the minimum number of larger drives you need today, leaving some bays open for future expansion.  That spreads their potential failure dates out more as well as letting the NAS run cooler till you put in the rest.  If you do end up leaving bays open, I hope you retained the air "dams" that the unit shipped with.  ON a rack mount unit, they should be installed whenever a bay is not in use.

Use the RAID calculator to determine how much space you'll get from various drive configurations: Netgear RAID Configurator .

If you have installed apps and are going with the starting over approach, make sure you re-install them before you restore any saved configuration.

If you have a configuration that is hard to re-create (because of installs from SSH, for example), there is a "tricky" way to keep some of the configuration intact.  You destroy the volume, then replace the drives you need to, then re-create the volume.  As long as you retain at least one drive (which can also be replaced after the volume is created), you'll retain everything in the OS partition the volume destructiojn didn't change.  Note that this still destroys and re-creates the /home and /apps directories, so anything in those is not retained.  But they can be backed up via SSH.  It also destroys the data folder structure, which can still be re-created from a configuration backup.  You should do all this with power on, BTW, rebooting after the configuration restoration.

BTW, I recommend you go to at least OS 6.9.5 and set your NAS to inform you of updates based on "long-term support" (which is currently 6.9.6).  There are a lot of fixes from 6.9.0 to 6.9.5.