Modelling Approaches for Bio-Manufacturing Operations - Measurement, Monitoring, Modelling, and Control of Bioprocesses - page 88

Table 1 Some examples of typical scenarios examined by modelling approaches
Modelling
scenario

Example

Process design Determining which process flowsheet out of several alternatives is the best

one

Investment
decisions

Determining whether to build a new facility or contract out the manufacturing
process

Economic
evaluation

Determination of financial feasibility (NPV) of a project

Facility fit Determining whether a process as designed and at a specific scale can be

accommodated within the capabilities and footprint of the facility and
whether the available resources are sufficient to support manufacture
without causing bottlenecks. Simulation results could be used to determine
whether plant retrofitting is required

Scheduling Organising batches or campaigns to maximise throughput

Process
improvement

Determining how changing an existing process might affect its operating
capabilities e.g. the impact of increasing upstream titre upon downstream
scheduling and process duties, or moving to new or unconventional
technologies e.g. disposable systems versus stainless steel

process can cope with the potentially higher recovery and purification duty placed
upon it or whether the plant can supply adequate additional quantities of ancillary
services such as steam or water. Such insights can help to determine whether an
upstream improvement will really deliver whole process benefits in terms of
yields, costs, times and throughputs [ 16 , 35 ]. This is especially useful where the
impacts of process change are unexpected or counter-intuitive [ 43 ]. A classic
example considers a pair of steps in which a homogeniser used for cell rupture is
followed by a clarifying centrifugation step [ 16 ]. Although increasing the
homogeniser pressure or the number of passes can increase product release, it will
also micronise the debris, making it harder for the clarifying centrifuge to remove
debris from the supernatant. Hence there is a trade-off between the operation of
these two steps, and this would need to be determined on a case-by-case basis.
Evaluating the impact of process interactions and identifying conditions for every
individual unit operation that deliver the overall required process performance is a
task that is well suited to a computer simulation that can evaluate many combi-
nations of conditions to determine the best trade-off.

1.3 Challenges in Developing Bioprocess Models

Driven by the needs outlined in the previous section, modelling software has
gained prominence rapidly within the manufacturing sector as a whole, driven also
by a growth in the size, cost and intricacy of projects and the need to achieve
success the first time around [ 15 ]. Despite the aggressive deployment of simulators
for process design in sectors such as polymers or chemicals [ 25 ], however, as