Modelling Approaches for Bio-Manufacturing Operations - Measurement, Monitoring, Modelling, and Control of Bioprocesses - page 98

energy etc.) can enable a process development group to target optimisation efforts
at the most significant cost centres. Such methods have been used to explore a
number of issues in recent years, including:

• Deciding how to structure multiple campaigns within a multi-use facility
• Determining how increasing the number of manufactured batches per annum
affects throughput and scheduling
• Exploring how to manage process changes within an existing manufacturing
facility e.g. how upstream changes may affect downstream purification or
scheduling capabilities
• Evaluating whether to use stainless steel or disposable bioprocessing equipment
• Comparing the outcomes of different fermentation strategies e.g. batch, fed-
batch or perfusion cultures

The following sections outline some of these examples.
Example 1
Farid et al. [ 9 ] discuss the creation of a prototype in silico method for bio-
pharmaceutical manufacturing, driven by a hierarchical framework to maximise
user flexibility when constructing the simulation. The hierarchical framework is
modular and enables a simulation to be built to varying levels of detail depending
upon available information. Thus, additional details can be added whenever nee-
ded, enabling a production batch or campaign to be represented at different levels
of complexity; For example, simulating tasks at a very high level can deliver an
overview of the process to obtain a summary of key technical and financial out-
comes, whereas drilling down to lower levels enables the higher-level activities to
be split into individual tasks of increasing definition, with a concomitant increase
in the amount and accuracy of data that are required. In the hierarchical decom-
position, a facility can be said to house one or more manufacturing campaigns,
which can be broken down into individual feed/in-process batches, which com-
prise an ordered series of unit operations and ancillary supplies. These can be split
into a set of individual unit operations and associated specific tasks, all requiring
their own resources and with associated costs, resource utilisation profiles and
material balancing properties. Hence, using a hierarchical approach, one can
obtain many different pieces of knowledge such as:

• Facility level, e.g. capital expenditure, ancillary equipment requirements,

ancillary costs and resource pools
• Campaign level, e.g. the number of campaigns scheduled in a year (especially
important for cases such as contract manufacturers where batches from different
customers need to fit in around one another), operating expenditure (direct and
indirect) and the final manufactured product mass
• Batch level, e.g. the number of batches, batch time and cost, productivity and
failure rates
• Unit operation level, e.g. the time taken to complete a task/sub-task, the
expenditure associated with those specific tasks and resource requirements for
those tasks