After all, the characters we met when Jemma and Daisy entered the Framework were different versions of those we’d come to know, and they’d built their own histories with each other.
It seems that at least one of the folks behind the scenes at Agents of S.H.I.E.L.D. is hoping for a spinoff about the Framework.
Why not explore those different histories in a new show, simply set before Jemma and Daisy turned up?
As long as it was handled correctly with regard to timing in the S.H.I.E.L.D. universe, a spinoff could definitely work.