Selecting Clones from the SSI Pools with Similar Product Quality for Later Stage Development
Although the materials from SSI pools have enabled the initiation of clinical material production immediately against the backdrop of pandemic outbreaks, clonal production cell lines are nevertheless required for later-stage process development and the subsequent greater-scale clinical and commercial manufacturing. With at least one batch of clinical materials generated by the Gen1 GMP campaign, the clonal production cell lines for the Gen2 GMP campaigns should particularly focus on the proximity of the product quality profiles along with the typical emphasis on productivity. For instance, there was one COVID-19 mAb molecule, whose transfectant cell pools were cloned in parallel with the Gen1 GMP production, to initiate the Gen2 development. From the clone screening results, the top clone candidates displayed a wide distribution of titer (Fig. 4A), as well as a broad kaleidoscope of glycan profiles (Fig. 4B) and charge variant profiles (Fig. 4C). Such observation of widespread variety should be largely attributed to the diversity of the transfectant cells in the SSI pool, which provides excellent flexibility and convenience for clone selection to match Gen1 materials. The candidates with both the closest product quality attributes to the GMP materials and the higher titer were considered the final clone candidates for the following Gen2 activities, to which the process and assay used for Gen1 should be mostly applicable. With the platform process, similar product quality was obtained between Gen1 and Gen2 (Fig. 4D).