NOVEMBER 2019
While the UK is a world
leader in vaccine
science, the urgency
and scale under which
COVID-19 vaccines are
needed is expected to
put manufacturers under
tremendous pressure to deliver.
One of the challenges that will need
to be tackled early on is meeting the
billion-dose demand using current
facilities of finite capacity.
Teams at Imperial College
London and Oxford University are
among those working to develop a
viable vaccine through networks,
such as the Imperial Network for
Vaccine Research, the Future
Targeted Healthcare
Manufacturing Hub, and the two
Future Vaccine Manufacturing
Research Hubs led by Imperial and
UCL/Oxford. The Government is
supporting these efforts with
funding and by having established
the Vaccine Taskforce which brings
together governmental, academic
and industrial partners .
However, a particularly
pressing issue the UK faces is that it
has a low number of plants with the
capacity to produce vaccines on a
large scale. Completion of the
Vaccines Manufacturing and
Innovation Centre (VMIC) in Oxford
has been fast-tracked to 2021 and
will contribute towards meeting
the forecasted demand. But even if
facilities are able to meet demand
in terms of production, they will
need to address potential
bottlenecks in their processes and
ensure stability of supply chains,
which will be crucial to delivering
vaccines to the population.
This is where engineers can
make a significant contribution.
Using modelling we run
simulations for the different
vaccine platform scenarios while
clinical trials are ongoing. This
means that once a vaccine
formulation has received
regulatory approval, we will be in a
position to recommend to
manufacturers which production
setup can deliver the best results.
Timing is a significant factor.
Scaling up UK
vaccine manufacture
Prof Nilay Shah, Head of Chemical Engineering at
Imperial College London, examines the engineering
challenges of rapidly scaling up vaccine production.
Conventional vaccine development,
pre-clinical testing and clinicwal
testing takes around 8–14 years, and
production process development,
facility construction, validation
and start-up takes 6–9 years. These
timeframes are incompatible with
the timelines indicated by a
pandemic-response vaccine
production, so teams are working
hard to try and fast-track this to
12-18 months. This leaves
manufacturers with little room for
long-term planning and
investment.
The challenge of upscaling and
modifying facilities in such a short
timeframe is compounded by the
vast range of vaccine platform
technologies on trial. In the UK,
COVID-19 vaccines are expected
from two main platforms, the RNA
and the chimpanzee adenovirus
(ChAd) vaccine vector. Each has a
different formulation, specific
upstream production and
downstream requirements.
Without knowing which they will
be expected to produce,
manufacturers are going to find it
difficult to fully prepare their
facilities for the task ahead.
We are currently assessing the
effectiveness of bulk vaccine
production, which traditionally
uses dedicated, large production
plants. We are also looking at a
different approach, and evaluating
new rapid-response vaccine
June 2020 / www.theengineer.co.uk 12
production platforms, which offer
high productivity in small-scale
processes. The ideal solution would
be developing a manufacturing
design that utilises both properties
to produce a large amount of
vaccines, fast.
Established technologies have
the advantage of existing knowhow
shared among several
organisations, so tech transfer to
multiple partners that
manufacture in parallel is possible,
including contract development
and manufacturing organisations.
This would enable rapid
deployment of existing assets and
process optimisation through
shared technical knowledge.
On the other hand, emerging
technologies such as the RNA
platform have very high specific
productivity, which leads to small
manufacturing footprint. This
means two things: they can easily
benefit from single-use
technologies to establish a
brand-new manufacturing facility
and can be just as easily scaled out
or decentralised to ease the
pressure on supply chain.
Both of these platforms
produce a bulk drug product. This
must then be filled into a final
delivery form, such as vials. This
latter step could well be the
bottleneck, especially in the UK.
Novel dosage forms such as
200-dose bags are being explored to
increase capacity; these would of
course mean that the final
administration process would
change somewhat.
Another key challenge the UK
vaccine manufacturing sector faces
is that of supply chains for the
acquisition of critical raw
materials, as normal routes are
affected by closed border and
limited transportation services. We
have already seen the difficulties
the UK Government faced in
securing PPE and medical supplies
from other countries, and we must
learn lessons from this to ensure
the UK is not left behind when a
vaccine becomes available. At the
other end, distribution must be
flexible to ensure vaccine
availability where it is most needed.
Initially, this is expected to be in
priority groups including
healthcare and other key workers,
and vulnerable groups.
Engineering models use a
systems engineering approach,
which will be essential to
manufacturing a COVID-19 vaccine
by accounting for capacity
limitations, supply chain
disruption and distribution
networks across the whole
manufacturing process. Taking this
approach enables us to find and
address bottlenecks, optimise
production and identify scenarios
in which the largest vaccine
demand is met in the shortest time
under resource constraints whilst
maintaining cost effectiveness
where possible. This will be vital if
we are to be successful in delivering
a vaccine for COVID-19 and
returning to pre-pandemic life.
With input from (all from
Imperial College London):
Dr Benoit Chachuat, Reader in
Process Systems Engineering
Dr Zoltán Kis, Research Associate
in the Imperial Future Vaccine
Manufacturing Hub
Dr Cleo Kontoravdi, Reader in
Biosystems Engineering
Dr Maria Papathanasiou, Lecturer
in Life Science Systems Engineering
VIEWPOINT
Professor Nilay Shah
/www.theengineer.co.uk