Host cell proteins (HCPs) pose a potential safety risk for biologic or proteinaceous drug compounds. As therapeutically relevant biomolecules are often produced in a biological expression system, remnants from the host cell can be co-purified during the manufacturing process. These host-cell proteins (HCPs) can, even at low levels, negatively impact the stability and functionality of the product. Therefore, regulatory agencies demand identification and risk analysis of all residual host cell derived contaminations during the drug approval process. Even for approved drugs, HCPs need to be routinely monitored and exactly quantified in every production batch of a drug. To address the regulatory requirements, manufacturers need to optimize the production process to reduce the amount of host cell derived contaminations as much as possible and to establish a surveillance process to monitor the removal of HCPs during production. The most commonly used method to determine the amount of HCPs in pharmaceutical industry currently is ELISA. However, this method often relies on polyclonal antibodies directed against the most common HCPs or against several proteins at once. The detection and quantification of known HCPs is highly dependent on the quality of the antibodies and gives no detailed information on which proteins have been detected. Our mass spectrometry based technology enables the unbiased detection of HCPs with high sensitivity and precision without the need for antibodies. Combined with our proprietary QconCAT technology, the detected HCPs can be quantitatively determined for each production batch.