In the course of product manufacturing, a number of chemicals are typically added upstream as part of the bioprocess to improve on product expression and recovery. These chemicals are almost entirely removed during the downstream purification process; however, residual levels of these agents may be left within the bulk drug substance and drug product. To ensure that the level of these agents is within safe amounts, highly sensitive analytical methods need to be used for detection and quantification of such residuals.
Along with process residuals, there is also the possibility for product-related impurities to be carried through the manufacturing and purification process. These impurities, including host cell proteins, host cell DNA, N-terminal truncations and other potential modifications, may cause adverse reactions in animals and humans, and therefore, assays must be employed to ensure that any impurities present are below pre-determined acceptable levels.
- IPTG (isopropylthio-beta-D-galactoside)
- PEI (polyethylenimine)
- Triton X-100
- Polysorbate (Tween) 20/80
- Protein A
- Growth Factors
- CHO/E. coli HCP
- N-Terminal Truncations
- Oxidation/Deamidation (PTMs)
- Disulfide Bridge Scrambling (misfolding)
- C-Terminal Integrity/Multiple Lysines