Polysorbate Degradation and Particle Formation in a High Concentration mAb: Formulation Strategies to Minimize Effect of Enzymatic Polysorbate Degradation

The measurement and control of high-risk host cell proteins for polysorbate degradation in biologics formulation

“…The defining characteristic of SH superfamily members is the presence of a nucleophilic serine in their active site. Although not every lipase/esterase is from the SH superfamily, chemical probes against SHs have been demonstrated to block PS degradation in a time- and dose-dependent manner [ 10 ], which was also confirmed by other studies using similar chemical probes or SH inhibitors [ 15 , 43 ]. Our previous study also indicated that chemical probes against SHs with different mechanisms of action may provide synergistic or complementary information for inhibition or enrichment of various classes of lipases/esterases [ 10 ].…”

“…For example, there are six groups of PLA2 enzymes, out of which four groups are considered as SHs, and the other two subtypes of PLA2 utilize His as the active site [ 47 ]. Interestingly, various chemical probes or inhibitors against SHs have been shown to almost completely block PS degradation [ 10 , 15 , 43 ], which indicates those lipases/esterases, which are not in the SH family, may not be expressed by CHO, or not secreted as HCPs. Second, not all SHs identified by ABPP have activities on PS degradation.…”

“…To explore other formulation options for PS degradation, Roy et al. investigated a batch of high concentration (>100 mg/mL) mAb DP where subvisible particles formed abruptly after prolonged storage at 5 °C [ 43 ]. The work summarized the effectiveness of different formulation strategies for managing HCPs and FA particles and found that the concentration of FA composition of PSs was significant factors in particle development [ 43 ].…”

“…investigated a batch of high concentration (>100 mg/mL) mAb DP where subvisible particles formed abruptly after prolonged storage at 5 °C [ 43 ]. The work summarized the effectiveness of different formulation strategies for managing HCPs and FA particles and found that the concentration of FA composition of PSs was significant factors in particle development [ 43 ]. Solubilizers, such as Brij L23 and cyclodextrin (HPβCD), and alternative surfactants, such as poloxamer 188, were all shown to be effective means of preventing particle formation [ 43 ].…”

“…The work summarized the effectiveness of different formulation strategies for managing HCPs and FA particles and found that the concentration of FA composition of PSs was significant factors in particle development [ 43 ]. Solubilizers, such as Brij L23 and cyclodextrin (HPβCD), and alternative surfactants, such as poloxamer 188, were all shown to be effective means of preventing particle formation [ 43 ]. Lipase inhibitor, AA26–9 as a broad spectrum SH inhibitor, proved to be a simple means to prevent PS degradation.…”