The concept of intensified design of experiments allows a faster screening of the given design space with the risk to introduce an irreversible impact of previous parameter settings on the cells. The main objective of this study was to investigate the individual impacts of mild and rigorous intra-experimental key parameter shifts on the culture performance and cell metabolism of an antibody producing CHO cell line. To elucidate such possible effects, we performed semi-continuous CHO perfusion processes in 10 mL spin tubes for 21 days in steady state. Herein, we introduced parameter shifts in pH, glucose concentration in the medium, osmolality, and medium blending ratio, and calculated cell specific cell rates. Our results indicated significant changes in cell growth, metabolism, and productivity due to intra-experimental parameter shifts. Increasing the pH to 7.4 for example, led to constrained cell growth but increased glucose consumption and lactate production. Increasing the osmolality in the culture media mainly increased the cell diameter and in return the specific antibody productivity. Increasing the glucose concentration in the medium impacted cell growth and metabolic parameters, namely qGlc, qLac, qAsp, and qGlu. While some parameter shifts did not even induce a significant rate change, others did, but the shift back to control settings also allowed for a corresponding readjustment of rates. However, if the conditions within an experiment are changed, the experiments must be designed to avoid rigorous shifts. In this aspect, we could show that cells irreversibly change their behavior when media blending experiments are performed.