Dr Michael Levis and Bernhard Burger of Siegfried share the combination of the real and digital worlds in chemical process development
Figure 1 - Prerequisites for a predictive model toolbox
Toolboxes for process development
Chemical transformations to the desired molecule are mostly well understood in classical process development . Scale-up follows well-established procedures . It starts with lab development followed by piloting and then to manufacturingscale equipment . However , scale-up still carries some risks . With the trend to shorten development time for new pharmaceutical entities , it has become necessary to reduce these risks in order to facilitate direct scaleup to manufacturing or validation of the first pilot batches . Smart solutions are needed for this task .
Challenges in scale-up
Scale-up surprises are found mostly in ' simple ' work-up procedures and physical-chemical transformations like phase separations , crystallisation or drying . Looking closer , it is obvious that most scale-up problems cluster either around heterogeneous multiphase systems or kinetic controlled reactions . So these are definitely of high interest . 1 However , these process steps are standardised in unit operations and can be described well by physicalmathematical equations . Software tools like Matlab , Aspen , ChemCad or Dynochem assist the chemical engineer to design the process and equipment for scale-up . Fluid dynamics in reactors are described by software like VisiMix . Statistical methods like Design of Experiment ( DoE ) approaches are also well established . So , why are these operations still so challenging ? How can we improve scale-up success from lab direct to manufacturing ? One explanation may be that the approaches described above are based on significant amounts of integer data from lab experiments , the manufacturing plant and a detailed , in-depth process understanding . The collaboration and expertise of subject matter experts from different departments is needed . Therefore , the ' activation energy ' needed to study these alleged simple operations in detail is quite high .
‘ Siegfried toolbox ’ approach
Siegfried has established a series of toolboxes to control these chemical
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