Protein purification: aspects of processes for pharmaceutical products.

The concept of purity is addressed for proteins as drugs. In addition to a short description of general techniques, emphasis is given to a discussion of special protein impurities and contaminants from the host cell of process additives. This includes the host homologue to the product and biologically active molecules and the quantitation of host cell proteins. Of special concern are closely related non functional proteins from the gene for the protein product itself. They pose the question of how a 'pure' protein can be defined, and to what extent potential heterogeneities caused by the purification method represent a risk. Most relevant are 'invisible' contaminants such as potential virus including the BSE agent. Critical aspects will be discussed of the current rationale for a strategy to arrive at safe biological products. The limitations of current virus enumeration methods are discussed in relation to technical limitations to prove the efficiency of virus removal steps. Another limitation is the nature of the protein product and its individual resistance to denaturing conditions in virus inactivation steps. This is amply demonstrated by the lack of methods for inactivation of the BSE agent maintaining the native state of proteins. As a general recommendation it is proposed to base risk assessment on scientific data and come to scientifically defined criteria of acceptance in both the global and national communities. This will facilitate bringing new biopharmaceuticals to the benefit of patients in the shortest period of time.