(506b) A Plant-Wide Dynamic Model of a Continuous Pharmaceutical Process

The pharmaceutical industry is undergoing rapid changes. Economic, environmental, health and safety requirements in conjunction with the regulatory environment are driving the sector towards more efficient processes. This requires innovation and cutting edge scientific, engineering knowledge and quality management systems. As a result, shifting from the traditional batch-wise to continuous pharmaceutical manufacturing (CPM) becomes a relevant alternative. In addition, the use of new process analytical technology (PAT), particularly on line, enables engineers to get better understanding and control of the underlying physical and chemical phenomena and makes it possible to build efficient CPM plants.

In this work, a plant-wide dynamic model of a continuous pharmaceutical pilot plant, including upstream and downstream units, is presented. This model is used to study the effect of design parameters such as purge ratio, reactor and crystallizer volumes on yield and purity. The objective is to minimize off-spec tablets production, particularly during the start up. The main specification used are the impurities levels. Impurities can arise out of raw materials, reagents, intermediates used in synthesis or bio-synthesis, by-products, degradation products, residual solvents or isomers. These impurities can affect safety and also efficacy of the drug. Therefore, a high level of purity of drug substance and the control of the impurities profile are important criteria in manufacturing of a safe and efficient drug. In the present work, all raw materials, solvent and excepients are considered to be pure, and only impurities that are from reactions (i.e. by-products, isomers) and residual reagents, intermediates and solvents are considered.