Control of Viruses in Pharmaceutical Products

CONTROL OF VIRUSES IN PHARMACEUTICAL PRODUCTS

The presence of certain viruses needs to be controlled in pharmaceutical products derived from human and animal origin. This includes blood products such as human plasma for fractionation intended for the manufacture of human antithrombin III, human coagulation factor VII, VIII, IX, XI, dried prothrombin complex, dried fibrinogen, normal immunoglobulin, human α₁proteinase inhibitor, and human von Willebrand factor, for which tests for the presence of antibodies against HIV1 and HIV2, hepatitis B surface antigen (HBsAg), and antibodies against hepatitis C virus are required. For the urine-derived urofollitropin (obtained from postmenopausal women), tests for hepatitis virus antigens and HIV antigen are needed.

The risk of a pharmaceutical product being contaminated by viruses depends mainly on the origin of the product component (e.g. species, organ, tissue), the history of the donor, the amount of material used, the manufacturing process and its capacity to remove/ destroy any contaminants. In addition, the infectivity and pathogenicity of possible viral contaminants must be taken into consideration, notably when considering the route of administration of the medicinal product (i.e. transdermal delivery would carry less risk than an injection). A risk assessment is generally carried out for these products containing a component from human or animal origin, which takes into consideration factors affecting the potential level of infectious particles and those related to the use of the product.

Thus stringent controls are applied to the raw materials, in process samples and to the final product. In addition, one or more validated procedures to remove or destroy viruses can be applied. The type of inactivation measures used must be validated against a range of representative viruses (i.e. enveloped, nonenveloped, DNA, and RNA viruses) with different degrees of resistance to that type of treatment. Furthermore, early inactivation limits the extent of contamination. For the preparation of vaccines, the inactivation process must ensure that it does not affect the antigenicity while killing the virus and other potential contaminants such as mycoplasmas; for example for the preparation of influenza vaccine, the inactivation process chosen must cause minimum alteration of the haemagglutinin and neuraminidase antigens.