EU/PICs GMP Guide Annex 2 paragraph 67 requires that intermediates at their maximum in-process hold periods
Some European inspectorates have interpreted this as the requirement to execute stability studies of Drug Products where intermediates and active ingredients are held until the end of shelf life. How can we approach this challenge as this can be difficult and costly?
Hello. I see that the EU Inspectorates may have jumped lanes from the Paragraph 67 requirements,
which addresses end of shelf life intermediates and APIs undergoing manufacturing in-process hold
periods vs end of shelf life intermediates and APIs impact on finished product shelf life. This second
issue has been raised by inspectors from time to time and at least several pharmaceutical companies I
am acquainted with have arranged studies to satisfy those questions, though as you mentioned, it is
difficult, costly, and time consuming to obtain/arrange for components that are near their expiry or re-
test dates. I have not heard that the issue is raised frequently. Since the more recent PIC/S requirement
extends the concept to materials in use during in-process hold times, we might address both scenarios
by paying attention to expiry dates of materials ordered or selected for manufacturing and then
deliberately stretching their hold times to the maximum allowed by our internal procedures. Having
data on hand from our best efforts toward the worst case scenarios should provide justification for
having made good-faith efforts at compliance. However, it remains impractical to routinely sit and wait
for our components to age-out before making critical batches. What have the rest of you readers
experienced along these lines?