Recorded Version of the webinar "How Well Do You Know Your Molecule? Application of Advanced Mass Spectrometry for Complex Disulfide and In Vivo CQA Mapping" 21th Jan. 2021

The focus is on two specific applications of advanced Mass Spectrometry (MS) for the development of complex biologics. These applications include mapping of disulfide linkages of complex biologics and the application of advanced MS for Critical Quality Attribute (CQA) mapping of a biologic in vivo.

Higher order structure (HOS) is a CQA because it reflects both CMC/process consistency and functional integrity of the biologic drug product. Most biologic therapeutics contain Cys and disulfide bonds (DSBs) and are known to play critical roles in the structural stability and efficacy of protein biopharmaceuticals. The accurate characterization of disulfide linkages is therefore critical in ensuring consistent structural, stability and efficacy profiles of a biopharmaceutical throughout its clinical development. Confirmation of DSB integrity/similarity in vivo can support regulatory filings and approval while evaluating potential clinical impact (safety and efficacy). 

In Vivo CQA Mapping is a second approach that can be used to understand the relationship between specific drug structures and clinical parameters to accelerate and de-risk advanced biologic drug development programs. Complex and engineered biologics can benefit from detailed characterization to better understand the molecule/platform. The presenters will discuss the importance of characterizing and monitoring cysteine and disulfide bonds in biologic drug products which can be used to guide strategic thinking about development of the biologic based on specific composition.