Determination of the Limit for Cell Age for Production Sample Clauses

Determination of the Limit for Cell Age for Production. This is a requirement by ICH5B as well as a pertinent study performed to ensure that the cell line will carry the plasmid through to the age required for the production fermentor. The limit for in vitro cell age for production will be derived from production cells expanded under pilot-scale conditions to mimic the production in vitro cell age or beyond. This will be accomplished by expanding the cell line from vial to shake flask to 30L fermentor and again to the 30L fermentor (using equivalent inoculum) to mimic the future production age in the 500 L fermentor. This study has also been referred to as a plasmid stability test. At this point the production cells will be examined using different dilutions on both selective and non-selective agars to determine the purity and plasmid retention of the production cells at this stage. Viability can also be determined at this point. It is recommended to expand the cell age past the planned production age to justify expansion of cell line to a later age (i.e. larger scale) that might be required in the future of the L-DOS47 development. The expression construct of the production cells at this cell age will also be analyzed at this point. The protein coding sequence of the expression construct in the production cells will be verified by nucleic acid testing or analysis of the final protein product. This will provide assurance that at the next planned production scale (500L) the cell line has the ability to produce comparable results as those established at the 20L scale (or age). Through this study, BioVectra will be able to establish an acceptable level of plasmid loss or protein titer that can be applied as an acceptance specification for later development batches. Site cGMP API Facility Fermentor Shake flasks, 30L - 30 L (22L) Time 2 weeks Documentation Protocol for the study Deliverables Report for Cell Age Determination for Production Cells and Laboratory notebook references
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