TABLE IX

Detailed Control Strategy Map for Quality Attributes

CQAaControl ElementControl Implemented
Total protein concentrationElement 2Mixing speed and time in formulation tank, mixing speed and time in intermediate vessel, stoppage times during filling
Element 5Incoming DSb release testing
Total protein concentration release testing
Element 6Total protein concentration stability testing
Bound proteinElement 2Mixing speed and time in formulation tank after addition of Subfamily A and B
Element 5Bound protein release testing
Element 6Bound protein stability testing
PurityElement 2Ambient temperature exposure and time through the filling, shipping, and packaging operations
Element 5Incoming DS purity release testing
Purity release testing
Element 6Purity stability testing
SterilityElement 1Prefiltration bioburden of buffer (IPT-C)c
Pre- and post-filtration filter integrity test (IPT-C)
Pressure decay testing of AlPO4d cans (IPT-C)
Element 2Hold time and temperature during formulation and filling
Element 5Incoming DS bioburden release testing
Sterility release testing
Element 6Sterility stability testing

  • ↵a CQA is critical quality attribute.

  • ↵b DS is drug substance.

  • ↵c IPT-C is in-process test for control.

  • ↵d AlPO4 is aluminum phosphate.