TY - JOUR
T1 - Enabling precision manufacturing of active pharmaceutical ingredients: workflow for seeded cooling continuous crystallisations
AU - Brown, Cameron J.
AU - McGlone, Thomas
AU - Yerdelen, Stephanie
AU - Srirambhatla, Vijay
AU - Mabbott, Fraser
AU - Gurung, Rajesh
AU - Briuglia, Maria L.
AU - Ahmed, Bilal
AU - Polyzois, Hector
AU - McGinty, John
AU - Perciballi, Francesca
AU - Fysikopoulos, Dimitris
AU - MacFhionnghaile, Pól
AU - Siddique, Humera
AU - Raval, Vishal
AU - Harrington, Tomás S.
AU - Vassileiou, Antony D.
AU - Robertson, Murray
AU - Prasad, Elke
AU - Johnston, Andrea
AU - Johnston, Blair
AU - Nordon, Alison
AU - Srai, Jagjit S.
AU - Halbert, Gavin
AU - ter Horst, Joop H.
AU - Price, Chris J.
AU - Rielly, Chris D
AU - Sefcik, Jan
AU - Florence, Alastair J.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Continuous manufacturing is widely used for the production of commodity products. Currently, it is attracting increasing interest from the pharmaceutical industry and regulatory agencies as a means to provide a consistent supply of medicines. Crystallisation is a key operation in the isolation of the majority of pharmaceuticals and has been demonstrated in a continuous manner on a number of compounds using a range of processing technologies and scales. Whilst basic design principles for crystallisations and continuous processes are known, applying these in the context of rapid pharmaceutical process development with the associated constraints of speed to market and limited material availability is challenging. A systematic approach for continuous crystallisation process design is required to avoid the risk that decisions made on one aspect of the process conspire to make a later development step or steps, either for crystallisation or another unit operation, more difficult. In response to this industry challenge, an innovative system-wide approach to decision making has been developed to support rapid, systematic, and efficient continuous seeded cooling crystallisation process design. For continuous crystallisation, the goal is to develop and operate a robust, consistent process with tight control of particle attributes. Here, an innovative system-based workflow is presented that addresses this challenge. The aim, methodology, key decisions and output at each at stage are defined and a case study is presented demonstrating the successful application of the workflow for the rapid design of processes to produce kilo quantities of product with distinct, specified attributes suited to the pharmaceutical development environment. This work concludes with a vision for future applications of workflows in continuous manufacturing development to achieve rapid performance based design of pharmaceuticals.
AB - Continuous manufacturing is widely used for the production of commodity products. Currently, it is attracting increasing interest from the pharmaceutical industry and regulatory agencies as a means to provide a consistent supply of medicines. Crystallisation is a key operation in the isolation of the majority of pharmaceuticals and has been demonstrated in a continuous manner on a number of compounds using a range of processing technologies and scales. Whilst basic design principles for crystallisations and continuous processes are known, applying these in the context of rapid pharmaceutical process development with the associated constraints of speed to market and limited material availability is challenging. A systematic approach for continuous crystallisation process design is required to avoid the risk that decisions made on one aspect of the process conspire to make a later development step or steps, either for crystallisation or another unit operation, more difficult. In response to this industry challenge, an innovative system-wide approach to decision making has been developed to support rapid, systematic, and efficient continuous seeded cooling crystallisation process design. For continuous crystallisation, the goal is to develop and operate a robust, consistent process with tight control of particle attributes. Here, an innovative system-based workflow is presented that addresses this challenge. The aim, methodology, key decisions and output at each at stage are defined and a case study is presented demonstrating the successful application of the workflow for the rapid design of processes to produce kilo quantities of product with distinct, specified attributes suited to the pharmaceutical development environment. This work concludes with a vision for future applications of workflows in continuous manufacturing development to achieve rapid performance based design of pharmaceuticals.
U2 - 10.1039/c7me00096k
DO - 10.1039/c7me00096k
M3 - Article
VL - 3
SP - 518
EP - 549
JO - Molecular Systems Design and Engineering
JF - Molecular Systems Design and Engineering
SN - 2058-9689
IS - 3
ER -