Mammalian cell culture process is widely being used in the biopharmaceutical industry to produce various therapeutics and diagnostics across the globe. The article sheds light onto the major unit operations employed in the industry for primary recovery of the protein. The clarification efficiency, protein recovery and the economics play the major role in deciding which unit operation to be used for clarifying the cell mass from the product. Centrifugation and depth filtration are the most popular ways of extracting the product initially, post-bioreactor stage. The trials and scale up calculations at the developmental stage based on the cell removal efficiency, processing time, contaminant reduction, and overall cost enables the drug manufacturer to select the optimal unit operation.