ABSTRACT
Peptic cleavage of horse plasma IgG is a common procedure for the preparation of F(ab)(2) products for human use, such as antivenin and antitoxin. The removal of the Fc fragment from the IgG molecule by enzymatic cleavage at low pH, ensures fewer side-effects of the F(ab)(2) product for passive immunotherapy compared with the whole IgG molecule. Since the starting material may be contaminated by zoonotic horse viruses, it is necessary to demonstrate the removal or inactivation of possible viral contaminants. Guidelines for performing such studies were published by the Commission for Plasma-Derived Medical Products (CPMP), and updated by the Committee for Proprietary Medical Products. It is recommended that viral clearance studies be performed on scaled down production processes that have been identified as possibly contributing to virus clearance and spiking of a model virus to the starting material. The model virus should be non-pathogenic but closely related to the potential infective virus. By quantifying the amount of virus in the product before and after the production process, the amount of virus cleared can be determined. Log(10) reductions of the order of 4 logs or more, and a biphasic inactivation curve (fast initial phase followed by a slower phase), are indicative of a clearance effect with a particular test virus under investigation.
