Improving DNA Removal from Bioprocess Purification Processes

Many new biological drug products produced using recombinant DNA technology, such as monoclonal antibodies, are produced in cell culture. The host cell produces the therapeutic proteins that are often secreted outside the cell into the surrounding culture medium. Purification of the therapeutic proteins requires separation of the host cell mass from the extracellularly secreted proteins followed by an extensive series of downstream purification steps. Production of these therapeutic proteins is regulated by the Food and Drug Administration (FDA) Center for Biologics Evaluation and Research (CBER). CBER provides guidelines for biologically produced drugs including suggested limitations on final product impurities. Because therapeutic proteins such as monoclonal antibodies are produced in cell culture, impurities can result from the host cells, or cell substrates. Examples of these impurities are host cell protein and host cell DNA. In, Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use, February 28, 1997, CBER states that “It is suggested that, wherever possible, the final product contain no more than 100 pg cellular DNA per dose.”

In any purification process it is desirable to remove impurities as early in the process as possible. This 3M Purification Application Brief addresses removal of DNA using cellulosic depth filters. Depth filtration is often employed for the first purification step, separation of cell mass from therapeutic proteins.