Course Description:
Polysorbates (mainly PS20 and PS80) are critical excipients in (bio-)pharmaceutical formulations that protect the contained therapeutic proteins from interfacial stress. The polysorbates are complex in composition due to their synthetic scheme, applying mixtures of starting materials, harsh synthetic conditions and only rudimentary purification of intermediates and the final products. The complexity increases due to the presence of susceptible chemical structural features that are prone to oxidative and hydrolytic degradation, such as ether and ester linkages, as well as sites of unsaturation in esterified fatty acids. It is therefore of utmost importance to control the quality of polysorbates in the raw material, and in the drug product formulation. The presentation will focus on the application of control strategies through proper analytics. Routine analytics that can be applied in a cGMP environment (FMA, ELSD, CAD, free fatty acid analysis, peroxide assay, etc.), as well as special analytics focusing on root cause elucidations in case of issues with polysorbate quality (particle analysis by spectroscopy and MS, fatty acid profiles, Lonza proprietary assay for detecting lipolytic activity in Biologics drug substance), are discussed. A further focus is on the control of polysorbate stability towards oxidative degradation by addition of antioxidants to the polysorbate raw materials. We show – by application of the above discussed analytics – that the end points of polysorbate oxidation, e.g. reduction in micellar concentration, peroxide formation, free fatty acid formation, and the formation of previously unreported – toxic and reactive – oxidation products, can be prevented in the raw materials, as well as in Biologics drug products containing stabilized polysorbate.
The live version of this recording took place on April 14, 2021 and features
a presentation by Michael Jahn, Ph.D.
Who should participate:
- Analytical chemists
- QA/QC analysts
- R&D scientists, managers
- Team members in CMC development projects
- Manufacturing scientists, managers
- Regulatory affairs specialists
- Contract research organizations
- Contract manufacturing organizations
Access Duration:Access to this course expires 60 days from the date of registration or until you mark the course ‘Complete’ – whichever occurs first.