Future Work

Biotechnology simulation is a rapidly advancing tool for biopharmaceutical manufacture. It allows the rapid assessment of a large number of options to be made when development goes beyond the level of initial laboratory studies. The decision- support tool developed in this thesis could evolve into a powerful tool for assisting decision-making. The framework established lays a strong foundation for exploring further work that can be used to address key issues in the industry. There are clearly many potential areas available for improving and extending the functionalities of the tool. The future work proposed in this section would be essential to enhance further

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the capabilities and robustness of the tool to aid the process of decision-making.

Several examples are pointed out and discussed below.

• Improving coding efficiency o f the tool

As discussed in Chapter 6, the simulation of each Monte Carlo run required a substantial amount of time. The computational speed of the tool could be improved by to coding the mass balance calculations in Excel. This would greatly reduce the number of blocks required to configure each unit operation and less computational time would be needed to initialise and process these blocks during the simulation. In addition, simple calculations of the process yields for each unit operation would be sufficient instead of using the rigorous mass balance calculations adopted in this thesis.

• Customisation o f new unit operations

The construction of the tool in a modular and extensible manner has facilitated the development of applications and allowed the developer to extend new features with ease. Such customisation should enable the impact of new manufacturing technologies to be assessed based on running costs and manufacturing performance.

The ability of the tool to build and customise new unit operations is demonstrated in a parallel study carried out at UCL (Mustafa et al., 2004). In this work, techniques such as expanded bed adsorption (EBA) chromatography are explored and developed in the software package. A case study is set up to compare the process and business benefits of a conventional process route employing packed chromatography beds and an alternative that uses EBA. The next phase of the study aims to investigate the potential feasibility of an EBA retrofit within a conventional packed-bed based process.

• Modelling o f explicit manufacturing tasks

In order to simplify the tool implementation process, material preparation steps were omitted from the modelling process. For instance, media and buffer are assumed to arrive pre-made in disposable bags. In future work, these activities could be modelled explicitly to achieve a more complete analysis. The incorporation of such preparation steps is essential to an examination of the impact on the resultant cost of goods and demand on resources, such as operator and materials. The modelling of

these ancillary tasks could be achieved by communication with the finance and manufacturing departments of the companies so as to determine the relevant costs and typical raw materials demand.

• Integration with drug development pathway

In addition to the work presented in this thesis, parallel work (Rajapakse et al., 2004) has focused on simulating the activities for portfolio management during biopharmaceutical drug development from drug discovery to market launch. Linking such a framework with the model of biopharmaceutical manufacture, as described in this thesis, would allow the impact of manufacturing decisions to be evaluated based on development timescales and costs, as well as manufacturing performance such as resource utilisation and cost of goods.

• Linkage to a sophisticated database

The data for populating the model was obtained from an existing UCL database and verified through discussions with industrial experts and biopharmaceutical vendors.

Microsoft Excel has been employed as the database providing a transparent interface to the Extend platform. A more sophisticated database (e.g. SQL, Oracle) could enhance the performance of the simulation tool. These databases offer more powerful capacities for organizing, managing and retrieving data. This needs to incorporate manufacturing data for different production processes for the various types of products.

The future work discussed in this section would be essential to capture pertinent features relating to biomanufacture and to enhance the capabilities the tool. In addition to improving the features of the decision-support tool, the tool could be used to investigate other industrially-related case studies. The case studies presented in this thesis have illustrated the application of the decision-support tool to assess the viability of manufacturing options in terms of process and economic aspects. The tool could be used to investigate novel manufacturing techniques so as to gain insights into real manufacturing situations. For instance, production of antibody- based proteins in transgenic goats, chickens and various plant varieties has been recently developed to achieve high yields at a potential lower cost of goods and

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-Chapter 7. Conclusions and Future Work

capital investment. A detailed analysis of transgenic production is essential to provide a clear perception of these new process options.

Further simulation studies using the tool could be applied to the ultra scale-down project currently undertaken at UCL (Titchener-Hooker et al., 2001). The ultra scale-down mimics methodology allows the rapid prediction of the best way in which to produce complex biopharmaceuticals during the early stages of biopharmaceutical development pathway and where only small volumes of material are available for study. Such methods alone are inadequate to predict completely the production performance. The decision-support tool could be employed to supplement the scale-down and ultra scale-down strategies by allowing a capacity to ask “what i f ’ questions and to link the different scales of operation.

In conclusion, the tool developed in this thesis has generated new areas for further investigation. The development of more sophisticated simulation capabilities would increase the functionalities of the tool and enable more complex and rigorous modelling to be accomplished. The application of industrial-related case studies provides insights into real manufacturing situations and aids the evaluation of process scenarios. The simulation tool possesses great potential for growth as a computer-based decisional system to address strategic needs for the successful commercialisation of biopharmaceuticals. Such bioprocess simulators could become significant engineering tools for process design and development over the next decade.

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