(328d) The Development of an Integrated Control Strategy for a Continuous Primary Pharmaceutical Process

The Development of an Integrated Control Strategy for a Continuous Primary Pharmaceutical Process

Presented by: H. Robinson,

On behalf of: M. Berry, P. Shapland, P. Clements, M Hughes, S. Ukuser, N. Hodnett, P. Hamilton, I. Areri, M. Dumarey, G. Turner, C. Clarke, C. Mayes, G. Alford, H. Todd, L. Wong, W. Tan, G. Breen, A. Ochen and A. Richards.

In adopting continuous manufacturing techniques for the production of Active Pharmaceutical Ingredients (APIs), additional levers become available for process control, enabling a different approach to control strategy definition than that traditionally used in the batch environment.  In the presented example, the development of a flow process including five telescoped chemical transformations, in a single solvent system, followed by two batch crystallisations is discussed in the context of building an integrated operational and quality control strategy.  Fundamental understanding of the chemical reactions through kinetic modelling is combined with equipment characterisation, through methods such as residence time distribution measurements, and process behaviour understanding, to maximise experimentation efficiency and minimise scalability and operability risks.  Use of a quarter scale lab pilot rig to verify reaction conditions and control methodologies is also discussed, along with the use of PAT for development of understanding and operational multivariate modelling.  Understanding gathered from the pilot scale rig is then used to advise the control system philosophy to deliver the automated operational control of the process.