We have submitted the following abstract to BOPA for this year’s symposium.
Title Monoclonal antibodies: Functional activity improvements at SPC shelf life limits
Introduction Monoclonal antibody (mAb) therapeutics are one of the fastest growing sectors in the pharmaceutical industry and have already established themselves as frontline therapies in oncology. These drugs are often assigned short shelf lives once prepared for administration, typically 24 to 48 hours, however SPC’s for several of these drugs recommend they be used immediately following preparation.
Aims The aim of our research was to evaluate the physical, chemical and functional stability of several mAb therapeutics used in oncology, comparing their characteristics immediately after preparation with that at the limit of their SPC shelf life.
Methods Physical/Chemical analysis of each antibody was performed using SE-HPLC, circular dichroism (VT-CD), SDS-page, pH, visual inspection, dynamic light scattering (DLS), Flowcam imaging and LC-mass spectroscopy (LCMS). Functional activity was measured using cell based assays that were specific for each antibody. Each antibody was evaluated immediately following preparation as well as at its SPC designated shelf life.
Discussion Analysis of the stability data generated from SE-HPLC, VT-CD, pH, visual inspection, SDS-page, LC-MS and DLS techniques, revealed that no significant differences could be detected between freshly prepared samples and those tested at the limit of their assigned SPC shelf-life. However, Flowcam imaging of samples did demonstrate significant differences in the number of sub-visible particles (>1um) present. Surprisingly, samples tested at the limit of their shelf-life consistently contained fewer protein aggregates than freshly prepared samples. In addition, results from cell based functional activity tests demonstrated, consistently, that samples tested at the limit of their shelf-life had equivalent, or greater, functional activity than freshly prepared samples.
Conclusion Differences have been observed between the characteristics of several mAb therapeutics tested immediately after preparation and at the limit of their shelf-life. Surprising, we found the mAb’s at the limit of their shelf-life to be of equivalent, or better, functional activity with fewer aggregates.