(383b) INCOME Modular Plant for Pharmaceutical Processing

An integrated modular continuous multi-purpose pilot scale process plant has been built in the Institute of Chemical and Engineering Sciences, Singapore to research and develop advanced continuous pharmaceutical production techniques with improved efficiency and quality assurance to support the needs of both local and MNC manufacturers in primary pharmaceutical (active pharmaceutical ingredient) and fine chemicals. With a multi-disciplinary team under one roof, which specialises in process chemistry development, design, analytics, chemometrics, control and modelling, we focus on integrated solutions to processing problems which is distinct from other researches where individual technology fragments prevails.

The multipurpose continuous plant has been designed to carry out a range of pharmaceutical complex and multiphase synthetic reactions. Sitting along side with our existing kilo scale batch plant, in-situ comparisons can be done between batch and continuous implementations of the same process to substantiate some of the claims being made for the advantages of continuous processing. The flexible and mobile nature of the modular plant also enables research and development of the hybrid operation of batch and continuous process.

Through the identification of a number of ?unit operations? that could readily be used in several different processes and to enable simple re-configuration and rapid changeover between processes, we have built a number of mobile processing skids that can carry out generic processing tasks ? for example feeding at a controlled rate, mixing/reaction, heating/cooling, phase separation, etc. These skids are built to a standard geometry based on the size of a ?Singapore pallet? i.e. with a footprint that is either all of or half of a size of 1.0m x 1.2m, and a height in multiples of about 1.0m, for easy relocation and rearrangement. Each skid is equipped with the basic essential instrumentation and control elements, electrical, utility, vent and drain connections. A process is set up by simply placing the appropriate skids in contact with each other and ?plumbing? them together.

The control system has been designed to have a modular construction, flexible and reconfigurable to handle different types of control situations in different processes within a single uniform platform in a ?plug-and-play? manner. Real-time monitoring of the continuous process coupled with chemometrics modelling will be executed so as to enable control of continuous processes. This is challenging as it will involve data management of the enormous information flow and a mix of data formats (spectral, vector and scalar data). The control system is designed to have the ability to connect to third party software (e.g. Matlab) to handle the data for off-line and on-line usage and prediction. We envisage the cross-coupling of process information through the database server with chemometrics model(s), control system and third party systems will engender continuous process understanding, knowledge generation and management based on the concept of Quality by Design (QbD), Risk-based Approach, Criticality determination, Design Space specification, and Control Strategy outlined by the FDA and PAT guidelines.

The early experience and results of operating the newly built multi-purpose modular pilot plant in a continuous mode with the deployment of some of the aforementioned tools will be presented. An example for this continuous processing operation will be a chemistry which has been scaled up from lab bench to batch kilo scale.