Recent Scientific Case Studies
Despite substantial efforts utilizing a diverse set of biologic evaluation and high-throughput techniques to select candidates with the best chance of success in preclinical development, the vast majority of biologic drug molecules fail in clinical trials. With most biologic drugs, including gene therapies, failures are realized in late-stage development, after substantial investment has been made in a candidate. Here, we discuss the potential for improving identification of potentially successful biologic drugs and de-risking CMC and clinical designs earlier through strategic application of advanced mass spectrometry, and specifically, how detailed assessment of target engagement using HDX-MS and Native-MS analyses may provide understanding to guide biologic development decisions.
Host cell proteins (HCPs) are common impurities in biologic drug products and are an obligatory critical quality attribute (CQA). The individual protein contaminants that make up the HCP profile, however, may vary significantly among individual biologic products and expression systems. As such, the HCP profile must be analyzed to identify even low levels of potentially concerning species in a biologic drug to ensure safety and efficacy. This whitepaper reviews fundamental aspects of HCPs pertaining to biologic drug development and current and emerging approaches to HCP analysis.
Historically, only general biologic drug PK levels have been assessed in clinical subjects, while related drug sub-structures and post translational modifications (PTMs) have rarely been examined in vivo. Recent advances in mass spectrometry and related sample preparations are enabling detailed characterization of biologic drugs extracted from biologic tissues including serum and plasma PK samples. This letter highlights how “In Vivo CQA Mapping” can be used to understand the relationship between specific drug structures and clinical parameters to accelerate and de-risk advanced biologic drug development programs.
Related Content: In Vivo Peer Reviewed Publications
Comparative Study of Profiling Post-Translational Modifications of a Circulating Antibody Drug in Human With Different Capture Reagents
Quantitation and Pharmacokinetic Modeling of Therapeutic Antibody Quality Attributes in Human Studies
Assessing In Vivo Dynamics of Multiple Quality Attributes from a Therapeutic IgG4 Monoclonal Antibody Circulating in Cynomolgus Monkey