Enabling precision manufacturing of active pharmaceutical ingredients: workflow for seeded cooling continuous crystallisation

Research output: Contribution to journalArticle

Abstract

Continuous manufacturing is widely used for the production of commodity products. Currently, it is attracting increasing interest from 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 systems-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.
LanguageEnglish
Pages518-549
Number of pages32
JournalMolecular Systems Design & Engineering
Volume2018
Issue number3
Early online date20 Feb 2018
DOIs
StatePublished - 1 Jun 2018

Fingerprint

Workflow
Crystallization
Cooling
Pharmaceutical Preparations
Process design
Drug Industry
Medicine
Industry
Decision Making
Decision making
Availability
Technology
Processing

Keywords

  • crystallisation
  • crystallization
  • future manufacturing
  • continuous manufacturing

Cite this

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title = "Enabling precision manufacturing of active pharmaceutical ingredients: workflow for seeded cooling continuous crystallisation",
abstract = "Continuous manufacturing is widely used for the production of commodity products. Currently, it is attracting increasing interest from 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 systems-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.",
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author = "Brown, {Cameron J.} and Thomas McGlone and Stephanie Yerdelen and Vijay Srirambhatla and Fraser Mabbott and Rajesh Gurung and Briuglia, {Maria L.} and Bilal Ahmed and Hector Polyzois and John McGinty and Francesca Perciballi and Dimitris Fysikopoulos and P{\'o}l Macfhionnghaile and Humera Siddique and Vishal Raval and Harrington, {Tom{\'a}s S.} and Antony Vassileiou and Murray Robertson and Elke Prasad and Andrea Johnston and Blair Johnston and Alison Nordon and Jagjit Srai and Gavin Halbert and {Ter Horst}, {Joop H.} and Price, {Chris J.} and Rielly, {Chris D.} and Jan Sefcik and Florence, {Alastair J.}",
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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

AU - Robertson,Murray

AU - Prasad,Elke

AU - Johnston,Andrea

AU - Johnston,Blair

AU - Nordon,Alison

AU - Srai,Jagjit

AU - Halbert,Gavin

AU - Ter Horst,Joop H.

AU - Price,Chris J.

AU - Rielly,Chris D.

AU - Sefcik,Jan

AU - Florence,Alastair J.

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KW - crystallization

KW - future manufacturing

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