Putative Phospholipase B-like 2 (PLBD2) is not responsible for
polysorbate degradation in monoclonal antibody drug products
Abstract
Polysorbates (PS) are surfactants commonly added in a therapeutic
protein drug product as excipients to protect proteins from denaturation
and aggregation during storage, transportation, and delivery.
Significant degradation of PS in drug products could lead to shortened
drug shelf lives and PS-degrading activity in drug products must be
minimized. Identification of lipases that degrade PS could lead to
better process control in drug manufacturing. In 2016, phospholipase
B-like 2 (PLBD2) was proposed as a residual host cell protein
responsible for degrading PS20 in a drug formulation. We have carried
out a series of studies to verify the role of PLBD2 in degrading
polysorbates in drug products purified from recombinant Chinese Hamster
Ovary (CHO) cells. Genetic knock-out and immuno-depletion results showed
that when PLBD2 was removed or depleted, the degradation of PS20 or PS80
was neither diminished nor reduced. In addition, a quantitative analysis
of PLBD2 and PS20 degradation in multiple formulated mAb products did
not establish a correlation between the amount of PLBD2 and the level of
PS20 degradation. Collectively these results suggest that PLBD2 is not
the primary cause of polysorbate degradation in formulated drug products
purified using standard Protein A and ion exchange chromatography.