In October 2007, in the "Questions and Answers on Current Good Manufacturing
Practices", the successor document to the human Drug CGMP Notes, there was an
interesting question on sampling and on identity testing of starting materials
(active pharmaceutical ingredients (APIs) and excipients):
"How many containers of each component from each shipment must a firm sample and
test to comply with the CGMP requirements for identity testing? Do the CGMPs
permit the identity test on a pooled, or composite, sample of multiple
Brian Hasselbalch and Dr Steven Wolfgang from FDA (CDER) gave a very detailed
answer to that, which can be summarised as follows:
The CGMP regulations do not specify the number of containers from which samples
should be taken. However, the requirements laid down in 21 CFR 211.84(b) can be
summarised as a programme for sampling of APIs and excipients as follows:
- The samples must be representative.
- With regard to variability of starting materials, the
confidence intervals and the level of necessary precision, the number of
containers from which samples are taken as well as the amount of material
sampled must be based on statistical criteria
- The sampling plan must take account of the past quality
history of the supplier.
- The sample quantity must be big enough to perform analysis
and to keep reserve samples
The pharmaceutical company is required to develop an approach
that guarantees a high level of certainty that each container contains exactly
the material indicated on the label.
The CGMP regulations allow the pharmaceutical company to make its own decision
on how many samples are necessary for identity testing. If starting materials
are bought from traders, it is considered advisable to take a sample from each
container for identity testing.
What is surprising is the statement that "pre-shipment samples or so-called
'piggyback' samples are generally not acceptable".
Pooling, or compositing, samples from several containers is viewed as quite
possible, since the preamble for 21 CFR 211.84(c)(4) of 1978 declares that there
is no general prohibition on compositing samples from single containers.
The statements made here now comply in many points with the regulations laid
down in the EC GMP Guide and the European Annex 8 on the sampling of starting
We have linked the complete original text at the end of this news for your
Dr Günter Brendelberger
On behalf of the European Compliance Academy (ECA)
FDAs "Question and Answers on current Good Manufacturing Practices