Host cell proteins (HCPs) are considered a critical quality attribute and are linked to safety and efficacy of biotherapeutic products. Researchers have identified 10 HCPs in Chinese hamster ovary (CHO) that exhibit common characteristics of product association, coelution, and age‐dependent expression and therefore are “difficult to remove” during downstream purification. These include cathepsin D, clusterin, galectin‐3‐binding protein, G‐protein coupled receptor 56, lipoprotein lipase, metalloproteinase inhibitor, nidogen‐1 secreted protein acidic and rich in cysteine (SPARC), sulfated glycoprotein, and insulin‐like growth factor‐2 RNA‐binding protein. While the levels of HCPs in the investigated biosimilars were within the acceptable range of <100 ppm, certain “difficult to remove” HCPs were found in the biosimilar samples. This article aims to elucidate the underlying interactions between these “difficult to remove” HCPs and the mAb product. Surface study of rituximab exhibited unstable discontinuous patches of residues on the protein surface that have high propensity to get buried and lower the solvent exposed area. The higher order structure and the receptor binding were not affected, except for one of the biosimilars, owing to extremely low‐HCP levels in its final drug product. Finally, based on the combined experimental and computational data from this study, a probable mechanism of retention for the 10 HCPs is proposed. The results presented here can guide downstream process design or avenues for protein engineering during product discovery to achieve more effective removal of the impurities.

Many remote communities around the world cannot be physically or economically connected to an electrical grid. The main objective of the study of designing an inverter control that attains a lower distortion level in the voltage as well as current waveforms by incorporating an optimization algorithm. The controller should reduce the spikes at the transient loading point when the system is subjected to sudden load changes at the power generating units. And the system is to be integrated with the fuel system also to obtain energy efficiency. The fuel system would be connected in parallel to the DC voltage output of the solar/wind hybrid system. The final hybrid system with fuel cell integration was studied for the total harmonic distortion in the voltage and current waveform. The distortion level in the voltage waveform was found to be 0.25% and that in the current waveform was 1.84%. It is under the IEEE acceptable limits.