Speciality Chemicals Magazine SEPT / OCT 2022 | Page 14

Dr Michael Levis and Bernhard Burger of Siegfried share the combination of the real and digital worlds in chemical process development

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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