Quality Assessment of Biologics Drugs

Unlike small molecule drugs, biologics are produced in living systems and have, not only primary, but secondary, tertiary and possibly quaternary structures. Determination of a biologic drug's higher order structure is critical to ensure efficacy, stability and safety.

NMR is perfectly suited to evaluate protein structures and to assess whether critical changes have occurred in a biotherapeutic drug during development and manufacturing. Because of its intrinsically high information content, NMR is proving to be a uniquely valuable tool for the evaluation of HOS, reducing the number of techniques needed to characterize biotherapeutic drugs. Recent advances in data acquisition and analysis have ensured that it is now possible to study intact materials (including monoclonal antibodies) at natural abundance, under conditions that are physiologically relevant. The new BiologicsHOS software offers a tool box of 1D and 2D method to evaluate higher order structure of biotherapeutic drugs. Additionally, the assessment of similarity between a biosimilar drug and its reference material is now fast and easy, allowing rapid pass / fail evaluations to be made.

Finally, due to the quantitative nature of magnetic resonance and its selectivity, potency determination,1 impurity profiling2 and degradation studies (e.g. polysorbates) are performed directly enabling fast and easy testing without the need of response factor calculations, or the method redevelopment activities required by traditional LC methods, thereby saving time and reducing costs.

1. Bradley S. A., Jackson W. C., Mahoney P. P., Anal Chem. 91(3):1962-1967 (2019)

2. Skidmore K, Hewitt D, Kao YH., Biotechnol Prog. 28(6):1526-33 (2012)