I have a query regarding Reserve samples, in particular Blistered Tablet Reserve Samples.
We have many instances where a CMO is manufacturing bulk tablets for us and then they are sent to a packager to blister them. Currently the bulk manufacturers are holding reserve samples of the bulk tablets of an amount that is twice the amount needed for. Should we also be advising the packagers to hold twice the amount needed for testing after it has been blistered?
I am not sure right now if there is a product complaint should we instruct the manufacturer lab to test the bulk tablets or the blistered tablets.
As per 21 CFR part 211 of CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS by USFDA,
Sec. 211.170 Reserve samples.
(b) An appropriately identified reserve sample that is representative of each lot or batch of a drug product shall be retained and stored under conditions consistent with product labeling. The reserve sample shall be stored in the same immediate container-closure system in which the drug product is marketed or in one that has essentially the same characteristics. The reserve sample consists of at least twice the quantity necessary to perform all the required tests, except those for sterility and pyrogens.
Therefore, it is mandatory to retain a sufficient quantity of reserve samples from each lot / batch in the final pack (Blisters) in which it is marketed.
Additionally, to retain bulk tablets by the bulk manufacturer is also required to ensure that in case of any discrepancy or doubt the retained tablets can be checked.
In case of a product complaint, the complaint should be jointly investigated by the bulk tablets manufacturer and the packager to identify the root cause(s) and taking appropriate CAPA actions. For this purpose, tablets from reserve samples in bulk (from the bulk manufacturer) and tablets in blister packs (from the packager) of the same batch number can be compared, assessed and investigated based on the type of market complaint.