Overall Structure

3.5.1.1 The Evolutionary Process

Three versions of the framework were developed. Figures 3.3, 3.5 and 3.8 show the overall structures of the different versions while figures 3.4, 3.6 and 3.7 show the timelines for the corresponding modelling case studies to which they were applied.

As figure 3.3 shows, Version 1 of the framework consisted of scope definition, model characterisation and model construction. As the timeline in Figure 3.4 shows, the model took 7 months to build at the end of which a rebuild was necessary, thus extending the timeline even further. In fact the overall duration of the BioSynT case study was approximately 9 months. Section 3.5.1.3discusses the reasons for this.

Figure 3.5 shows Version 2 of the framework which expanded on the Problem Structuring phase of Version 1 by adding a non-coded description of the system. It also added a Design Phase, a model specific description of the system, mapping the system or process elements to the model elements. As the timeline in Figure 3.6 shows, the overall mAb case study took just under 5 months, with the actual model construction phase significantly reducing from 5.5 months to only 1 month.

However, the debugging stage did take longer than expected with a duration of 3 months. Section 3.5.1.3discusses the reasons for this.

Figure 3.8 shows Version 3 (final version) of the framework, which is very similar to Version 2 with the only difference being the addition of the templates. The library of templates were created to reduce not only the model build time but also the debugging time, by providing building blocks which could easily be used and debugged due to their standard nature. Figure 3.7 shows the projected timeline if the mAb case study were to be carried out again using the framework Version 3, showing that the overall duration would significantly reduce by 65%.

Figure 3.3 Proposed methodology for the different stages of model design and construct as part of the Standard Framework Version 1

Figure 3.4 Stages of BioSynT model build (Case study for Standard Framework Version 1).

Where

1. Given remit with a series of Gantt charts. No direct contact with client

2. Independent review of possible capacity management questions that could be asked

3. Began design of model based on predetermined standards and guidelines such as decomposition, resource modelling and data management

4. Began model construct based on standards and limited information given with remit.

5. Structure of model put into place. Initial elements added such as activities, database for data management, resources and cycle times.

6. First contact with client. Scope increased but no further information given.

7. Increased levels of complexity added to account for increased scope, largely based on assumptions. A few rules on resource usage added based on discussions

8. Second meeting with client. Some data provided - new information suggests that model contains too much unnecessary/redundant complexity based on previous assumptions. Decision point on how to proceed: revisions will mean more code, more rules and more data to manage, resulting in high levels of hidden and visual complexity. Model rebuild will mean more time dedicated to model construct however expected increase in model efficiency with new knowledge.

9. Model REBUILD

Figure 3.5 Proposed methodology for the different stages of model design and construct as part of the Standard Framework Version 2

Figure 3.6 Stages of mAb model build (Case study for Standard Framework Version 2)

  Where

1. Problem Structuring Phase I (2 days) 2. Problem Structuring Phase II (14 days) 3. Design (4 days)

4. Build (30 days) – including early version templates construct 5. Debugging (90 days)

(Validation occurred throughput the project with the help of system experts)

Figure 3.7 Projected Stages of mAb model build (Standard Framework Version 3)

Where

1. Problem Structuring Phase I (2 days) 2. Problem Structuring Phase II (14 days) 3. Design (4 days)

4. Build (15 days) 5. Debugging (15 days)

(Validation occurred throughput the project with the help of system experts)

- 81 -

+ Templates

What are the questions that need answering / the remit What are the desired results/outputs?

What data is available?

Metrics to measure against e.g. throughput, completion time

Model Characterisation Scope

Process Elements

Non-coded description of process using process terminology Text based

Diagrams Spreadsheets

Using the predefined list of questions based on Standard Version 1

Model Elements

Build Model Problem Structuring I

Problem Structuring II

Design

Construct

Model specific description of process using model terminology

Coded description of process Extend Model

Figure 3.8 Proposed methodology for the different stages of model design and construct as part of the Standard Framework Version 3

3.5.1.2 The Standard Framework Final Version

Since developed as part of an evolutionary process, Version 3 bares a similar resemblance to the first two versions, but with additional features such a more comprehensive methodology and a library of template blocks. Furthermore, a significant finding of this work is that in order to minimise the degree of customisation required the standard, and in particular the templates, should be created with a certain degree of inbuilt customisation. This move away from a completely generic framework inherently limits the number of systems for which the templates can be applied. As such, although the modelling methodology is a universal one and can be applied to any modelling activity of any system, the majority of the templates will be limited to the specific domain of biopharmaceutical manufacture. The following describes the key features of the standard framework Version 3.

The final version of the standard framework consists of three major parts:

(1) Methodology for model development (2) Standard templates for model construct (3) Standard set of questions to ask the client