Mettler Toledo recently published a white paper entitled ‘Process Analytical Technology (PAT) for Biotech: A Review of Recently Reported Applications in Fermentation and Bioprocessing.’ The paper explores how Process Analytical Technologies, or PATs, help optimise fermentation and bioprocess actions critical to pharmaceutical, specialty chemical, commodity chemical, and bulk fuel development and manufacturing.
‘PAT instrumentation, with applications from the laboratory to production scale, helps ensure bioprocesses are performing as designed to maximise batch yield and productivity,’ said Terry Redman, Product Manager at Mettler Toledo and principal author of the white paper.
Effective screening and optimisation for bioprocess development requires accurate monitoring and tight control of operating conditions. The Mettler Toledo literature review determined that PATs such as in situ monitoring are being used effectively to optimise bioprocesses in a manner unachievable by traditional methods of offline sampling.
‘In our analysis, it became clear that for complex cell systems, where flocculation and aggregation alter biomass concentration, simplistic measurements such as turbidity and optical density do not capture the entire picture. Systematically applied PATs, on the other hand, enhance process controls for better consistency,’ Redman explained.
‘Measurements such as Focused Beam Reflectance Measurement® (FBRM) provide precise particle population measurements sensitive to changes in cell count, dimension and shape, each of which has been directly correlated to biomass. Morphologic change mechanisms and their kinetics are better quantified, which allows for real-time cell population control,’ he added.
Benefits were found across all processes reviewed, including fermentation, biocatalysis, peptide synthesis, and protein and peptide crystallisation. Crystallisation – whether protein or small molecule – requires consideration of process parameters that affect crystal nucleation, growth, and agglomeration. Real-time particle characterisation has become standard PAT from early solubility curve determination to critical process optimization, ensuring consistency in scale-up.
Advanced PATs help identify relevant parameters for optimising chemical synthesis as well. Study results explored the relative influence of temperature and reagent concentrations on yield and selectivity while avoiding the cost and time delay involved in withdrawing, preparing, and analysing samples on an ongoing basis.
‘Across multiple processes and industries, PATs are being used to help ensure fermentation and bioprocessing exercises yield desired outcomes. The result is fewer pre-process experiments and more effective scale-up,’ concluded Redman.
Mettler Toledo specialists Urs Groth, Fabio Visentin, Dominique Hebrault, Ben Smith, Des O’Grady, and Brian O’Sullivan assisted Redman in the white paper’s creation.
To download a complete copy of “A Review of Recently Reported Applications in Fermentation and BioProcessing” for free, visit http://us.mt.com/us/en/home/supportive_content/White_Papers.pat-biotech.oneColEd.html.
Mettler Toledo’s global network of technology and application consultants possess extensive research and industry experience supporting bioprocess development and scale-up. Visit www.mt.com/autochem for information on our products/services and an extensive list of upcoming and on-demand webinars.