(661h) QbD and Continuous: A Step Change in Performance

Authors: 
Donnellan, P., University College Dublin
Traditionally the majority of active pharmaceutical compounds have been manufactured at large plant scales using batch methodologies. Continuous manufacturing is becoming an increasing attractive alternative however due to apparent benefits such as smaller manufacturing footprints, increased process safety, lower manufacturing costs and increased supply-chain flexibility. Realising all of the above benefits using conventional continuous equipment is however quite challenging and sometimes not achievable. In this project, a new approach to the design of continuous manufacturing platforms is being presented which is not restricted to using such conventional equipment but which is based around the bespoke design and manufacture of all unit operations, optimised to fit the specific process being examined. Processes are quantified in detail using methods such as computational fluid dynamics (CFD) leading to tailored equipment designs which can be manufactured with high precision using metallic 3D printing.

In order to demonstrate the suitability of applying this design approach to the entire manufacturing process, a case study is also presented in which two reactions are coupled together, followed by an extraction and wash step and a liquid-liquid separation. All unit operations within this platform are designed using fundamental engineering principles combined with numerical analyses (based upon the requirements of the specific process), prior to being 3D printed and combined to create a bespoke, sealed, hard-piped manufacturing system. The optimised design of the units enables extremely high throughput rates to be achieved corresponding to 580,000 kg/L/day (compared to an approximate batch productivity of 525kg/L/day).