tratified sampling” is the process of sampling dosage units at predefined intervals and

collectingrepresentative samples from specifically targeted locations in the compression /

filling operationthat have the greatest potential to yield extreme highs and lows in test
results. These test resultsare used to monitor the manufacturing process output that is most
responsible for causing
finished product variability. The test results can be used to develop a single control
procedure to
ensure adequate powder mix and uniform content in finished products.
Stratified sampling is recommended to be used when the population is known to have
several subdivisions (i.e., locations), which may give different results for the quality
characteristics measured.

The Stratified In-Process Dosage Unit Sampling and Assessment assist manufacturers of
human drug products in meeting the requirements of 21 CFR 211.110 for demonstrating the
adequacy of mixing to ensure uniformity of in-process powder blends and finished dosage
units.

This correlates the stratified sample data with the powder blend data, which inturn corelates
with the finished dosage unit data and assess uniformity of content. Stratified sampling
should be used for Exhibit batches, Process validation batches and routing manufacturing
of the batches. It e can be used to monitor active ingredient homogeneity of powder blends
and to ensure uniform content of the finished product for solid oral drug products.

The method assumes appropriate monitoring of all manufacturing steps as required by

the regulations or (ANDA/ NDA) application commitments.

The FDA expects that no significant differences should exist between in-process locations
that could affect finished product quality. Between- and within-location variability is a critical
component of finished product quality and therefore should be evaluated. Please refer to
ASTM E2709 and ASTM E2810 for further guidance on establishing acceptance criteria for
a stratified sampling plan.