Why do we performed stratified at compression stage ??
“Stratified sampling” is the process of sampling dosage units at predefined intervals and collecting
representative samples from specifically targeted locations in the compression / filling operation
that have the greatest potential to yield extreme highs and lows in test results. These test results
are 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.