Although E. Coli has proven itself an important, if not vital, player in the production of biopharmaceuticals, its use in upstream fermentation does not come without challenges and costs for downstream purification. At the start of purification, clarified cell lysate may have an endotoxin level greater than 1 billion EU/mL. By the time the material becomes a final formulated drug product, its endotoxin level must be reduced many orders of magnitude to meet the FDA standard of 5 EU/kg. However, due to the small size of individual endotoxin molecules, the ability to micellize into aggregates with molecular weights as high as 1 MDa and interact with other molecules at higher concentrations, and its pH and heat resistance, the challenges of endotoxin removal are well known. Here, we test the endotoxin reduction capabilities of several processes, namely anion exchange membranes, surfactant-based protocols, and spin columns. We also evaluate cleaning procedures for their effectiveness at depyrogenation and quantify the endotoxin level of a process development lab environment where bacterial fermentations are regularly performed to mitigate endotoxin cross contamination in the process development lab.