It is generally accepted in the industry to perform process validation on three consecutive lots. How does the Inspectorate view validation when reworking is required (i.e., three consecutive incidents will never happen)?

Reworking of a batch should be a very rare occurrence. As such, validation of reworking is not
considered mandatory as it is not generally feasible. The reworking should be carried out in accordance with
a defined procedure approved by Quality Control (QC) and with the conditions described in Interpretation 6
of Section C.02.014 Quality Control Department. This procedure should include supplementary measures and
testing during the reworking operations to ensure that the quality of the final product is not compromised.
It is mandatory that rework proposals and reworked product also be fully investigated with respect to impact
on release characteristics and potential impact on bio-availability. Changes in formulation due to reworks
including the incorporation of additional lubricant or dissolution aid or additional critical processes may
require comparative bio-availability studies. Furthermore concomitant stability studies must be undertaken on
reworked batches to ensure that critical characteristics are not compromised with time due to the rework.