ABSTRACT
This paper describes gamma irradiation of a biotherapeutic product under conditions (the Clearant Process") that protect proteins and foster inactivation of viruses and other pathogens. The treated product was immunoglobulin paste from cold ethanol fractionation of human plasma, a process intermediate in the production of intravenous immunoglobulin (IGIV). The frozen paste was irradiated on dry ice to 45 kGy, conditions that inactivate > or = 4 log10 of non-enveloped viruses and > or = 6 log10 of enveloped viruses. When IGIV purified from the irradiated paste was characterized, no protein aggregation, fragmentation, oxidation or denaturation was detected and Fab functionality remained intact.
Subject(s)
Immunoglobulins, Intravenous/radiation effects , Virus Inactivation/radiation effects , Chromatography, High Pressure Liquid , Circular Dichroism , Electrophoresis, Polyacrylamide Gel , Gamma Rays , Humans , Immunoglobulins, Intravenous/chemistry , Immunoglobulins, Intravenous/isolation & purification , In Vitro Techniques , Protein Conformation/radiation effects , Viruses/radiation effectsABSTRACT
A comparison of ultraviolet (UV) irradiation of two wavelength ranges UVB (280-320 nm) and UVC (lower than 280 nm) showed that UVC in particular could very effectively inactivate, in intravenous immunoglobulin (IVIG) and albumin preparations, non-enveloped and non-acid labile model viruses (i.e., Polio 2 and T4 phage) and dry heat-resistant viruses (vaccinia and T4 phage). This effective virucidal treatment (5 min, 5,000 J/m2 dose) was achieved before an unacceptable level of IVIG aggregates occurred. The use of UV irradiation to inactivate infectious agents could add safety and supplement current methods, e.g. solvent/detergent, low pH, which do not inactivate non-enveloped, non-acid labile or dry-heat-resistant viruses at present.
