This eBook explores the growing analytical challenges of managing host cell protein (HCP) impurities in biopharmaceutical manufacturing, with particular focus on complex biologics such as gene therapies and CHO-derived products. It examines the evolution of HCP analytics from early ELISA and Western blot methods to advanced orthogonal approaches combining Antibody Affinity Extraction (AAE™) with mass spectrometry, which enable more precise identification, coverage analysis, and absolute quantification of high-risk HCPs. A featured study demonstrates the utility of a parallel reaction monitoring (PRM) assay using stable isotope-labeled peptides to quantify six CHO HCP lipases at sub-ppm detection levels.