Introduction
A new generation of continuous
small-scale reactors been developed,
that promise to revolutionise the
manufacture of high-value, low volume
products.
These micro reactors can be used in
parallel, to achieve production scale-up
without the complexity of large-plant
design and operation. They offer
extraordinary flexibility and efficiency,
enabling the manufacture of a number
of products by rapidly adjusting
operating parameters between recipes.
Their design reduces waste, reduces
energy consumption, and requires a
much smaller solvent inventory than
equivalent bath reactors.
To exploit the full potential offered
by these reactors, two distinct areas
needed to be addressed. First,
for existing products: improved
automation is required during
normal manufacturing, to better
reject external disturbances such as
feedstock variation, to minimise waste.
Second, for new formulations: the
ability to identify - and drive the
process to - the operating conditions
required for achieving on-spec
products more rapidly, reducing timeto-market.
Finding a Solution
To address these challenges, Perceptive
Engineering led a collaborative
R&D project, in partnership with
AstraZeneca, the Centre for Process
Innovation Limited (CPI) and
the EPSRC Centre for Innovative
Manufacturing in Continuous
Manufacturing and Crystallisation
(CMAC), based at the University of
Strathclyde.
Perceptive Engineering Limited is
based at Sci-Tech in Daresbury, one
of the UK Government’s national
Science and Innovation campuses.
Drawing on their extensive experience
in Advanced Monitoring and Model-
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Predictive Control (MPC), Perceptive
used their proven software platform
PharmaMV™ to deliver far more
precise control of the reactor,
achieving the desired product
quality while optimising production
yield, ready for commercial scaleup.
Results
The results have been demonstrated
on model compounds such as lactose,
as well as products of true industrial
interest and the project has shown a
significant improvement in yield and
in the ability to tightly control particle
size distribution (PSD).
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Perceptive
used their proven
software platform
PharmaMV™ to deliver
far more precise control
of the reactor
• Increased yield: 26% higher
yield (vs batch) in continuous
crystallisation
• Consistent & higher product
quality: 2 fold reduction in span of
PSD vs stirred tank reactor
• Process intensification: Reduction
in Lactose crystallisation time from
16 hour to 5 hours
• Reduced resources: less operator
intervention, less waste
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However, these units do require high
levels of manual intervention, to
identify suitable operating conditions
and adjust the process as needed to
maintain final product quality. This
can be challenging: the design of the
reactors, and the ancillary equipment
they require, often results in complex
system interactions.
• ‘Dial a Particle’: user-defined
particle size characteristics,
automatically delivered by MPC
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Three demonstrator systems, complete
with Perceptive Engineering’s Advanced
Control and Monitoring platform, are
now available to the wider industrial
community through the CPI’s role as a
national CATAPULT centre and CMAC’s
status as an EPSRC national centre.
The project has been shortlisted for the
IChemE Global Innovation award.
To learn more about this project, or
about how PharmaMV™ can help
your own processes meet or exceed
their goals, please contact Perceptive
Engineering.
Perceptive Engineering Limited
Vanguard House
Keckwick Lane
Sci-Tech Daresbury
Cheshire WA4 4AB
United Kingdom
T: +44 1925 607150
W www.PerceptiveAPC.com
@ [email protected]