Continued Process Verification

In the past, validation of commercial manufacturing processes comprised three validation batches and was then considered complete. Since 2011 however, the expectations by regulatory authorities with respect to validation changed. Process validation should be an ongoing effort and should continue during commercial manufacturing. This is also known as “Continued process verification” (CPV). For this purpose process data are collected followed by statistical process control (SPC). By generating process control charts and the calculation of process capabilities it is possible to determine whether the manufacturing process remains in a state of control (validated state). Progress-PME experts have extensive knowledge of designing a CPV program for new as well as for legacy products. Their broad expertise comprises writing and implementation of CPV and SPC policies, performing of (daily) statistical process control and the interpretation of the results. In combination with their state of the art process validation knowledge they can support you to produce drug products which fulfil all quality requirements during the whole lifecycle of the drug product.

The CPV program is based on gained process knowledge derived during stage 1 (process design) and stage 2 (process qualification) of process validation. An important part of a CPV program is the monitoring of the commercial manufacturing process. By monitoring so called process inputs such as Critical Material Attributes (CMA) and Critical Process Parameters (CPP) it is possible to minimize process variability. If necessary the manufacturing process can be adjusted to ensure that the results of so called process outputs, such as Critical Quality Attributes (CQA), process times and yields will met the predefined quality requirements. The statistical evaluation of the process data is part of the yearly product evaluation (PQR/APR). In addition, the statistical evaluation is part of the quality system. They are an important source of information for:

  • The assessment of the impact of process deviations on the quality of the product
  • The assessment of process results and robustness
  • The assessment of the efficiency of implemented CAPA’s (Corrective Action Preventive Action) and changes
  • The implementation of process optimization including reduction of lead times
  • The transfer of the process of analytical methods as part of a technology transfer.