Dr. Marius Schmid is highly experienced in all aspects of biophysical analysis, previously as a senior scientist and Head of Analytical Ultracentrifugation (AUC) and AF4 at Coriolis Pharma. In 2019, he co-founded and became CEO of the Heidelberg-based Zentriforce Pharma Research GmbH, a CRO specializing in hydrodynamic analysis techniques for biopharmaceuticals and gene therapy products.
MS: The increasing interest in using AUC and asymmetrical flow field-flow fraction (AF4) as tools during biosimilar and gene therapy development was the main stimulus to found ZentriForce in 2019. Since then, we have extended our portfolio of analytical services, but AUC and AF4 remain our core techniques.
MS: Yes- definitely. We observe a steady increase in requests from the FDA and other authorities for the verification for purity assays by orthogonal techniques. These requests also result in a heightened awareness of the importance of orthogonal measurements among CMC experts. One example of this is verification of aggregate content determination via size exclusion chromatography by orthogonal methods as AF4 or AUC.
MS: We tackle a variety of challenges during comparative biosimilar analyses. Most stem from issues due to the formulation of the drug product or the nature of the molecules. Examples for challenging excipients are phenol and other aromatic solvents, for example meta-cresol, and sugars. API related challenges may be the small size of the API, for example peptides, glatiramer acetate and others, or modifications such as PEGylation. In all cases, it helps to have extensive experience working with a wide range of challenging APIs and formulations. I believe expertise is important for reliable method and experiment design.
MS: We have successfully analyzed a variety of viruses during the last few years, including AAVs, adenoviruses and phages. The aim of the analysis of Gene Therapy products is different than antibodies, for example. It can still be considered a purity analysis, but there are more dimensions of purity that must be addressed in gene therapy products in comparison to biosimilars.
While biosimilars, such as antibodies, mostly contain impurities like fragments or aggregates, AAV products additionally contain empty or partially loaded capsids. Thus, in order to determine the purity of a Gene Therapy product, we need to consider a separation of sample components in terms payload , as well as of mass. Analytical ultracentrifugation has proven to be the most reliable method for payload determination, while asymmetrical flow field flow fractionation is the most suitable technique for aggregate content determination in Gene Therapy products, due to its large measurement range from 1 nm to 1 µm.
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