Impact of photo-oxidation on long term storage of affinity chromatography media used in multi-specific antibody manufacturing processes.

Large scale manufacture of complex biotherapeutic formats such as multi-specific antibodies can require development of custom biomanufacturing platforms, particularly for purification processes. Substantial advances in affinity chromatography media have allowed monoclonal antibody-like processes for these formats, and simplified process development to enable fast speed to the clinic. Thorough assessment of chromatography media performance and stability is critical to ensure robust operation and consistent product quality over repeated cycles throughout its lifetime.

Leveraging light chain binding avidity for control of mispaired byproducts during production of asymmetric bispecific antibodies.

Many biotherapeutic formats leverage antibody light chain affinity chromatography to enable robust manufacturing processes and to streamline process development. These include multi-specific antibody and antibody fragment platforms which are often designed for specific capture purification methods that can provide efficient removal of commonly expressed product-related impurities. Recently, several accounts of product-related impurity separation by leveraging binding avidity during affinity chromatography have been described in the literature.

Identification of compendial nonionic detergents for the replacement of Triton X-100 in bioprocessing.

We have systematically investigated six compendial nonionic detergents as potential replacements for Triton ×-100 in bioprocessing applications. Use of compendial raw materials in cGMP bioprocessing is advantageous for a variety of reasons including material specifications developed to meet stringent pharmaceutical product quality requirements, regulatory familiarity and comfort, and availability from vendors experienced supplying the biopharmaceutical industry. We first examine material properties of the detergents themselves including melting point and viscosity.

Development and scale-up of a commercial fed batch refolding process for an anti-CD22 two chain immunotoxin.

We describe the development and scale-up of a novel two chain immunotoxin refolding process. This work provides a case study comparing a clinical manufacturing process and the commercial process developed to replace it. While the clinical process produced high quality material, it suffered from low yield and high yield variability.

Recovering corn germ enriched in recombinant protein by wet-fractionation.

Corn wet-fractionation processes (quick-germ fractionation and traditional wet milling) were evaluated as means of recovering fractions rich in recombinant collagen-related proteins that were targeted for expression in the germ (embryo) of transgenic corn. Transgenic corn lines accumulating a recombinant full-length human collagen type-I-alpha-1 (full-length rCIalpha1) or a 44-kDa rCIalpha1 fragment targeted for seed expression with an embryo-specific promoter were used. Factors to consider in efficient recovery processes are the distribution of the peptides among botanical parts and process recovery efficiency.