DoE-Based Development

They selected a representative formulation from their conventional fluid bed granulation batch process portfolio and focused on four key areas: time, quality, cost and agility. The immediate release character of the tablet and BCS Class 1 of the APIs involved enabled the team to apply for a biowaiver provided the dissolution profile was similar or identical to the batch-produced product. Production parameters were defined using a Design of Experiment (DoE) approach in a short period of time, 150 kg of product and few trials. Process stability and repeatability was established during a number of long runs using online measurement techniques.

When the process and tablet quality control (QC) data were thoroughly analyzed, Janssen was able to confirm the stability of the process and to evaluate any process sensitivity fluctuations caused by minor environmental changes. The excellent correlation between the process data and the tablet QC data enabled the team to confirm the process parameter settings and ranges and satisfactorily demonstrate process robustness. The repeat long runs helped the team to fully understand process and product behaviour at start-up, during routine operation and at shutdown, and to obtain a preliminary idea about potential process capability.

In Summary

The study showed that, using ConsiGma® technology, process development can be done in a very short time. Assuming development and commercial manufacturing is done on the ConsiGma®-25 line, technology transfer is redundant, resulting in a substantial time-to-market reduction and decreased costs. The agility of the system was shown during process development, resulting in effective and efficient DoE. Process stability and robustness have been proven during the long runs and real-time, in-line measurements have shown their ability to monitor the process based on predetermined intermediate and finished product attributes.