I do not own the game, but looked at previous versions and am looking at DDSPF2022.

The questions are about the DDSPF2022 game or the College game for 2021

How are plays called during a game?
Is it by tendencies (you set a percentage based upon the game situation)?
Is it you pick a pre-made play out of a playbook? If so how large is the playbook?
Can you, during a game, pick a runner and have him say run off tackle right or do you have to have a play pre-made for that?
Or is this a pure GM game where the plays called depend upon the Head Coach you hire?

If you're simming games the AI will use your scenarios and playbooks accordingly.

If you're playing the games out you can call whatever play you want whether it's in your playbook, a coaches playbook, or the default set of game plays. There are hundreds of plays across different formations already in the game.

If you want you can create custom plays that suit your play style and put them in your custom playbooks.

During the game you cannot set a specific runner... you set a personnel package that subs in the players in that package, but adjusted for tiredness, etc.