Batch Processes in chemistry
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Transcript of Batch Processes in chemistry
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Development of batch processesin the pharmaceutical industry
Sven Wagner
Traditional development froman engineering prospective
Chemistry is fixed
Detailed analysis of the process or chem. rxn
Generate process understanding, i.e. ratelaws with the kinetic parameters
Derive the best process parameters withrespect to the given frame work
Utilisation of the best suitable reactor type
Design unit operations based on physicalproperties
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The path to a new medicineYears 1 162 3 4 5 6 7 8 9 10 11 12 13 14 15
No. of compoundsUp to1,000,000 10-15
Drug Discovery Drug DevelopmentTarget and leadidentification
Leadoptimisation Concept testing
Developmentfor launch Launch
Clinical DevelopmentPhase I50-150people
Phase II100-200people
Phase III500-5,000people
Phase IV studies continue
Product lifecycle support
Toxicology and pharmacokinetic studies(absorption, distribution, metabolism, excretion)
Pharmaceutical and analytical development
Process chemistry and manufacturing
Registration and regulatory affairs
Sales and marketing (preparation, promotion, advertising and selling)
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Development constraints
Process
API quality
Robustness
(incl. by-products)
Costs
(chemicals &
manufacture)
Attrition risk
Process
Safety
Environmental impact
Regulatory requirements
Projected
peak volumes
Lead times
Patents
Complex and
changing chemistry
API delivery for
clinical trials during
development
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Flexibility, i.e. using ofbatch/semi-batch processing
Availability and versatility (rxn, separations etc)
Not process specific design
Relatively easy scaled from lab experiments
Batch/Semi-batch more robust to inaccurateknowledge about the process, i.e. allowingshorter lead times
easy cleaning
Risk minimisation for launch of product
Development challenges
Development of the chemistry typicallyiterative
Regulatory issues narrows possible changesto the process in later phases of development
Cost-benefit management
Balance potentially conflicting targets forseveral interest groups (e.g. regulatory vs.safety)
Increased pressure to reduce costs
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Engineering approach
Work in close collaboration with chemistry
Working in parallel
Strengthen background in physical organic chemistry,reaction engineering and synthetic chemistry tomaximise contribution to process design
Awareness training for chemists regarding masstransfer, mixing, process safety etc.
Utilising specialists and generalistsReaction
Engineering
PAT Crystallisation
Preparative
Chromato-
graphy
Chemical
Hazards
Operational
Hazards
Process
Development
Engineers
Engineering issues
Ensuring an efficient communication with other functions
Chemical Reaction Engineering
How to achieve best CRE impact during the processdevelopment?
How to gather high quality data in a short period oftime?
Balance between specialists and generalists critical mass
Preparative chromatography, CRE for batch processand Process Safety difficult to recruit in Sweden
Cost-benefit management of activities
Introduction of new technologies
