Purpose: The CIS43LS monoclonal antibody is currently in development at the Vaccine Research Center (NIH) for prophylactic and/or therapeutic treatment of malaria. The goal of this project is to optimize solution conditions towards the development of a stable liquid/frozen formulation at a concentration of ≥100mg/mL
In this study, data for physico-chemical properties and stability aspects of CIS43LS mAb were evaluated by Differential Scanning Calorimetry (DSC), SEC-HPLC, Micro-flow Imaging (MFI), Capillary Electrophoresis (CE), Spectroscopy and Dynamic Light Scattering (DLS).
An initial buffer DoE evaluated the effects of 3 buffer salts (Acetate-Phosphate, Citrate Phosphate and Histidine Phosphate) on the conformational and colloidal stability of CIS43LS at various NaCl concentrations and pH values between 5.5 and 7.2. It was observed that CIS43LS stability is dependent on pH, buffer component and salt concentration, with greater relative stability observed in Acetate Phosphate buffers A subsequent study evaluated the solubility of CIS43LS in lead formulations derived from the buffer DoE. CIS43LS was soluble and stable at approximately 100mg/mL. Excipient screening and optimization revealed that Sorbitol, Sucrose and Na Citrate provide increased stability in conjunction with an Acetate-phosphate based buffer. CIS43LS mAb was then formulated in three lead formulation buffers and stability is currently being monitored under proposed clinical storage and accelerated temperature stress conditions over 12 weeks.
An optimal combination of pH, ionic strength and buffer salts was identified to improve the conformation and colloidal stability of anti-malarial antibody CIS43LS. Stabilizing excipients were identified, and three candidate formulations were developed, all of which are potentially suitable for formulation of CIS43LS at ≥100 mg/mL under liquid and/or frozen conditions. The stability of CIS43LS in these buffers is currently being evaluated proposed clinical storage and accelerated temperature stress conditions for GMP buffer selection.
Lisa Kueltzo– Director, Formulation and Stabilization Sciences, Vaccine Production Program, National Institutes of Health (NIH), Gaithersburg, Maryland