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.
