Place of nanofiltration for assuring viral safety of biologicals

Viruses are nanometer size organisms (range from 18 to 250 nm) that can potentially contaminate the feedstocks from animal or human origins used to manufacture biopharmaceutical products. Various measures are taken to ensure the optimal viral safety of this class of products. Selection and screening of starting materials play an important role in safeguarding from the introduction of viruses into the downstream processing but they have limits in specificity and sensitivity. Purification methods of protein biopharmaceutical products may also contribute to viral reduction, but since viruses exhibit a wide range of biochemical characteristics and resistance to physico-chemical treatments, complete elimination of infectious agents is not guaranteed. Therefore, the viral safety of animal derived biopharmaceutical products is well recognized to rely largely upon the use of deliberately introduced and validated viral inactivation and/or removal steps. A major progress in viral safety has been made recently by the development and availability of biocompatible viral filtration (also known as nanofiltration) systems using membranes of a pore size as small as 15 nm; these systems are specifically designed to allow, depending upon membrane used, typically over 4 to 6 logs of virus removal under conditions ensuring good protein permeability and recovery. Validation studies and production experience throughout the world have demonstrated that viral nanofiltration is a robust and reliable viral reduction technique that can be applied to essentially all biological products. This review analyzes the virus risks of biopharmaceutical products (human plasma derivatives, horse and sheep plasma-derived products, recombinant proteins and monoclonal antibodies), the various viral inactivation methods used at present, and the increasing role that viral nanofiltration is playing in assuring the safety of biopharmaceutical products.