As has already been mentioned but to Add a few things extra
Additionally, specific to Big Sur macOS 11 and above. The Operating System resides in a Sealed and Read Only Volume that can not be opened by the User.
So in effect, either of the two mentioned Cleaner's will only be able to touch the User Account(s) folders " Home Folder(s)." and nothing more.
Further, the User only has Direct Control over that same " Home Folder (s) "
So, the " Unwanted Files " the user is interested in cleaning out will and do only reside in that very same " Home Folder(s)" .
If Empty Space is the real underlying issue for this computer ➡️
Rebuild the Spotlight index on your Mac
What is “Other” storage on a Mac, and how can I clean it out?
Free up storage space on your Mac
OmniDiskSweeper Safe to use
GrandPerspective
How to delete Time Machine snapshots on your Mac
See used and available storage space on your Mac
Locate backups of your iPhone, iPad, and iPod touch
Notation - If the user is using a cloning software like Carbon Copy Cloner - suggest tweaking the Safety Net Feature in this software. It may be making additional Snap Shots that are not being Cloned to the Eternal Drive. If this should be the case, these Snap Shot could be using additional space on the drive
The final word from Apple on Managing the " Other/ System Data “ Category
Other / System Data: Contains files that don’t fall into the categories listed here. This category primarily includes files and data used by the system, such as log files, caches, VM files, and other runtime system resources. Also included are temporary files, fonts, app support files, and plug-ins. You can't manage the contents of this category. The contents are managed by macOS, and the category varies in size depending on the current state of your Mac.
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