In the May 2008 edition of the Journal of Pharmaceutical Innovation [Volume 3: pages 105–112] an excellent article appears from Eli Lilly entitled "The Use of Routine Process Capability for the Determination of Process Parameter Criticality in Small-molecule API Synthesis".
The paper proposes that a CPP is truly critical only when variation over the range of (a multiple of) its common cause variability leads to an unacceptable CQA.
This concept could narrow the range of parameters requiring identification as critical in the CTD of a QbD submission, leaving open a broad design space composed of other non-critical (but important) factors.
The forthcoming DynoChem release will include quantification of criticality from this perspective, as well as general tools for design space exploration and risk quantification based on first principles process models.