If you subject the final API to reworking with a different solvent, where do you draw the line between being in compliance with GMPs and being out of compliance from a regulatory standpoint? Would you need to update your certificate of analysis to test for the additional solvent and notify the drug manufacturer of the reworked batch? If not, why?

Being in GMP compliance and being out of compliance with your filing is kind of no mans land,
because if you’re out of compliance with what you have filed, you’re not in a position to sell the
material. The requirements of the Agency relative to filing requirements are the driver when it
comes to rework. Use of another solvent is a trigger to notifying a user of an API and requires the
use of the rework section of Q7A.