Suggestion for a

Strategy for the ESBES-Working Group

M³C

Motivations for the M³C White Paper

In order to establish a set of clear and well-defined strategies for the Modelling Measurement Monitoring and Control (M³C) working group, it is necessary to define the context in which M³C exists.

Firstly, the importance of maintaining the “open framework” in which this group operates should be emphasized. M³C is more of a “club” open to all active professionals across Europe rather than a formal organisation where a number of positions, a defined set of aims, and one uniting vision are established (see the separate organisational discussion put forward by Carl-Fredrik Mandenius).

Secondly, in order for M³C to be recognised as a key player within the Biochemical Engineering section of the European Federation of Biotechnology, it is necessary that the other working groups (Bioreactor Performance, Downstream processing and Biotransformations) recognize the M³C section as THE working group for “Measurement, Monitoring, Modelling and Control – M³C”. Models are preferentially used for monitoring, control and chemometrics. In practice this means that M³C is the natural contact point for in-depth knowledge transfer on M³C issues and a strong partner for the other working groups in organising sessions with common interests.

Measurement, monitoring, modelling and control have very broad definitions and it is very likely that an overlap exists between the different working groups. It is thus necessary to establish what these words means from an M³C perspective. The following definitions are proposed:

Measurement

The action of obtaining physical, chemical or biological data from physical, chemical or biological phenomena, independent of the time scale or integration with the processes from which the data are collected.

Monitoring

The action of obtaining on-line and/or at-line measurements that yield information about the physical, chemical or biological phenomena under study within a comparatively short time. Information obtained is used to follow the evolution of one or more biotransformations.

Modelling

Establish a formal mathematical description of the physical and/or chemical and/or biological phenomena based on the physical and/or chemical and/or biological measurements obtained as well as on the signals monitored, with the purpose of understanding and controling the bioprocesses and biotransformations involved.

Control

Bring the state of a process, i.e. one or more process measurements or monitored process signals to the desired value and maintain them at the desired value or trajectory for the duration of the bioprocess. It is important to notice that the choice of the desired value is the solution of a specific optimisation problem.

Based on these concepts, the M³C working group that met in Lyngby on October 2002 decided to foster the research, development, and diffusion of the following activities:

• The development and/or adaptation of novel measurement techniques. These should be used for monitoring and fault detection of bioprocesses. In defining what to measure we look into where monitoring is needed from up-stream to downstream. This is a subject in which a close collaboration with the downstream processing and the bioreactor performance working groups can be established. Extended uses for monitoring measures can be forseen if the collected samples fall outside the general “process scheme oriented designs”, e.g. in the measurement of difficult parameters in biological fluids in general. We do not include e.g. bioanalytical systems in health care / “point of care” situations within the Core of the defined M³C issues, but it is thought useful to bridge in between these areas of application of measurements.

• The development of numerical methods to extract information from the vast amount of experimental data collected in the experimental or industrial plant. One of the most important issues to study is on how to contribute in “finding out what to measure, how to measure it and the relevance of the obtained measurements”.

• The use of measurements and numerical methods to monitor the physiological signals of interest. This information should be used to derive and/or improve models describing the performance of the cells.

• To exploit this knowledge in order to define an optimal strategy to maximize a defined process objective. Novel control methodologies should be explored which guarantee that the desired optimum can be achieved.

October 2002, revised and approved August 2003

Gunnar Hörnsten, Sergio Valentinotti and Berhard Sonnleitner.