A Novel MATLAB®-Algorithm-Based Video Analysis to Quantitatively Determine Solution Creeping in Intact Pharmaceutical Glass Vials

During the filling process of a biopharmaceutical drug product (DP), a liquid DP film might creep up the inner vial wall which is barely discernible, appears as milky-white haze after lyophilisation and is known as fogging. Creeping and fogging are mainly dependent on the primary packaging material surface and its hydration, vial preparation process as well as DP composition. The occurrence of both can impede visual inspection and might lead to DP rejection. Hence, our studies focused on the early detection of liquid solution and glass vial surface interaction directly after filling. For a fast and highly sensitive evaluation a novel video-based analysis was used. To our knowledge, this is the first time a MATLAB®-algorithm-based video analysis was applied to quantitatively determine creeping time-resolved. Furthermore, creeping in dependence of vial processing sites, surfactant type and concentration, filling temperature, and vial format were investigated. The results were verified using orthogonal conventional methods such as surface tension, wetting behaviour, and contact angle measurements, as well as ToF-SIMS, ICP-MS, and SEM. Additionally, the methods applied were assessed regarding their cross-validation capability. The observations indicate that the vial preparation process can have a pronounced impact on alteration of the glass vial surface and related creeping behaviour of the filled solution

Data of rational process optimization for the production of a full IgG and its Fab fragment from hybridoma cells

This data article focuses on the production of monoclonal antibodies (mAb) and their fragments Fab and F(ab′)2. Here, we present the data of an optimization protocol to improve the product yield of a hybridoma cell process using a Design of Experiment (DoE) strategy. Furthermore, the data of the evaluated conditions were used to test feeding strategies in shake flasks. They were verified in controlled 2 L fed-batch bioreactor processes. Supplementing the culture medium with human insulin-like growth factor-I (IGF-I) and Pluronic F-68, as well as a nutrient rich additive for fed-batch, resulted in improved cell growth correlating with a 7 day elongated process time and a 4.5 fold higher product titer. Finally, a rapid Fab generation protocol and the respective data are presented using different papain digestion and a camelid anti-kappa light chain VHH affinity ligand. Keywords: Design of Experiment, Hybridoma, Papain, Production, Fab, F(ab′)2, Bioproces