Analytical monitoring of critical quality attributes (CQAs) of a rapidly growing pipeline of new-format NBE candidates has become an increasing challenge for the pharmaceutical industry for both throughput and specificity. Traditional protein analytical methods such as liquid chromatography or electrophoresis are often limited in their ability to provide sufficient information on the CQA situation of development candidates. Moreover, in-depth analysis of development candidates, which delivers an understanding of the structure-function relationship, has traditionally been applied only during extended characterization in later development stages – typically phase 3 clinical trials. As a result of this back-loaded analytical strategy, pitfalls associated with CMC, such as amino acid variants or site-specific modifications directly compromising the modes of action (MOA), occasionally go undetected until very late stages and impede the regulatory approval process.
There has recently been a paradigm shift in the analytical strategy of the biopharmaceutical industry to overcome these challenges. This new approach, in which CQAs are elucidated at much earlier phases, typically in the form of development feasibility assessments in late research, delivers a solid foundation of knowledge on structure and function, which then serves as a basis for producing and controlling high-quality biologics. The core technology of this in-depth analytical strategy is mass spectrometry, which, because it delivers concise information on multiple characteristics, is also known as the multi-attribute method (MAM).
Here, we provide an overview of the use and advantages of mass spectrometry, in particular of intact mass analysis for CQA evaluation of biologics.