Comprehensive Assessment of Pharmacokinetics, Pharmacodynamics, and Tolerability of Ligelizumab in Healthy Volunteers and Patients with Chronic Spontaneous Urticaria to Optimize Its Subcutaneous Delivery System.

Ligelizumab is a highly potent, humanized IgG1, anti-IgE monoclonal antibody. To explore its optimal subcutaneous delivery, the pharmacokinetics (PK), pharmacodynamics (PD), and tolerability of ligelizumab from two Phase 1 studies in healthy volunteers (HVs) and four Phase 2 and 3 studies in patients with chronic spontaneous urticaria (CSU) were assessed. Using different injection volumes or durations of a liquid-in-vial (LIVI) formulation or different formulations (LIVI vs. prefilled syringe (PFS)), single-dose ligelizumab showed comparable PK exposure in HVs. Steady-state exposure of ligelizumab was also comparable between LIVI and PFS following multiple dosing in CSU patients. The total IgE level (a PD marker) and tolerability were similar between the two formulations in both HVs and patients. Furthermore, the PK, total IgE, and tolerability were comparable for PFS administered either by patients or healthcare providers (HCPs). Collective evidence demonstrated that the injection duration or volume, formulation, or administrator had no apparent impact on the PK, PD, and tolerability of ligelizumab, supporting no clinically relevant difference between LIVI and PFS, and that PFS can be administered by patients or HCPs. This report provides a comprehensive assessment based on data of multiple clinical endpoints from both HVs and patients to inform formulation development and commercial use of a monoclonal antibody.

Oxygen transfer in a laboratory stirred tank bioreactor during Mammalian cell culture cultivation.

The influence of power consumption on the volumetric mass transfer coefficient was studied in a 5 liter stirred tank bioreactor during cultivation of a recombinant Chinese Hamster Ovary (CHO) cell line, which requires low aeration and mixing intensity. Under these conditions and at high cell concentrations, oxygen mass transfer coefficient and consequently volumetric oxygen mass transfer rate was not sufficient for the oxygen requirements. This problem was successfully solved by introducing pure oxygen into the bioreactor and the oxygen mass balance was studied. For that purpose, respiration rate as a function of cell concentration, as well as volumetric oxygen mass transfer rate at different operating conditions were measured. Graphical presentation of the results show the process control possibilities and the role of mixing intensity necessary to ensure that there is sufficient oxygen supply for a given cell concentration and respiration rate.