For human drugs, according to Interpretation 6.1 under C.02.009 Raw Material Testing, each container
of a lot of a raw material must be tested for the identity of its contents. Therefore, each container of all raw
materials, including excipients and active pharmaceutical ingredients (API), must be opened and sampled.
Then, 2 options are available:
1) To test every sample for ID using a discriminating method (it is not mandatory to perform all ID tests in
the specifications, for example United States Pharmacopoeia (USP), but the test must be specific).
2) If the raw material can be tested for potency, the other option is to mix and pool individual samples taken
from each containers in a composite sample but without exceeding 10 individual samples in a composite. A
specific ID test is then performed on each composite and, in addition, a potency test is performed to assure
the mass balance of the composite. (In such cases, an equal quantity of each individual sample in the
composite must be weighed to ensure that the mass balance is representative.)
As an example, say 72 containers of the same lot of a raw material are received. Each and all containers must
be opened and a sample taken from each container. After that, the first option is to test each sample for ID
(which implies 72 ID tests). The second option is to combine equal quantities of those individual samples in a
way that the number of samples in any composite does not exceed 10 and test those composites for ID and
potency. In this case, the easiest way to combine those samples would be 8 composites of 9 individual
samples. For a given composite, a potency result of 88.8 % or so would indicate that one of the containers
does not contain the right material as each individual sample contributes 1/9 or 11.11% of the total mass of
the composite (similarly a result of 77,7 % would indicate 2 containers with the wrong material). In such
case, each container selected for this particular composite would have to be tested for ID to pinpoint the one
(or more) containers with the wrong material.
However, the use of a composite sample to establish the ID of a raw material cannot be used when the
potency limits are too wide or, similarly, when the precision of the assay method is not sufficient to properly
establish the mass balance.
