Mammalian cells (particularly Chinese hamster ovary) have become the dominant system for the production of IgG based therapeutic antibodies due to their ability to produce properly folded and assembled heterologous proteins as well as their capability for post translational modifications. A prerequisite for the function of such IgG antibodies is their correct assembly into defined quaternary structures, composed of two heavy chain (HC) and two light chain (LC) polypeptides that form disulphide bonded HC2LC2 molecules. Folding, assembly and post-translational modifications occur within the ER where the molecule is subjected to rigorous quality control before being transported to the Golgi. IgG polypeptides sequentially interact with a range of molecular chaperones, foldases and oxioreductases present within the ER complex. The LC polypeptide can be secreted as both monomer and disulphide bonded dimer. Conversely, HC polypeptide secretion requires the presence of LC for secretion, the absence of which results in the HC polypeptide being retained in an unfolded state within the ER before being trafficked to the proteasome for degradation. Biochemical and physiological stimuli have been reported to impose stress on the ER and lead to the accumulation of unfolded or misfolded proteins within the cell. There is thus a need to understand the relationship between changes in physiochemical parameters in the bioreactor and the cellular molecular mechanisms allowing the secretion of misfolded/unfolded/cleaved proteins from the ER and the influence of cell culture supernatant on the structure and stability of fully secreted antibody and protein products.