A modified caprylic acid method for manufacturing immunoglobulin G from human plasma with high yield and efficient virus clearance
Article first published online: 20 DEC 2005
Volume 90, Issue 2, pages 97–104, February 2006
How to Cite
Parkkinen, J., Rahola, A., von Bonsdorff, L., Tölö, H. and Törmä, E. (2006), A modified caprylic acid method for manufacturing immunoglobulin G from human plasma with high yield and efficient virus clearance. Vox Sanguinis, 90: 97–104. doi: 10.1111/j.1423-0410.2005.00731.x
- Issue published online: 20 JAN 2006
- Article first published online: 20 DEC 2005
- Received: 23 August 2005, revised 28 September 2005, accepted 21 October 2005
- caprylic acid;
- intravenous immunoglobulin;
- polyethylene glycol
Background and Objectives The increasing demand for intravenous immunoglobulin (IVIG) necessitates the development of improved plasma fractionation methods, providing higher immunoglobulin G (IgG) recovery. Here, we describe a new IVIG production process resulting in a high yield of IgG and effective reduction of physico-chemically resistant viruses.
Materials and Methods IgG was purified from Cohn fraction II+III by caprylic acid treatment, polyethylene glycol precipitation, anion-exchange chromatography, nanofiltration and ultrafiltration. Stability of the purified IgG was studied in different formulations. Virus reduction was studied with two viruses: bovine viral diarrhoea virus, assessed by an infectivity assay; and human parvovirus B19, assessed by polymerase chain reaction.
Results The combination of caprylic acid treatment with polyethylene glycol precipitation and a single anion-exchange chromatography yielded polymer-free, pure IgG. The purified IgG could be filtered through a small pore-size virus filter (Millipore V-NFP) with high throughput and excellent yield. The formulated product was stable as a 100 g/l IgG solution. Bovine viral diarrhoea virus was effectively inactivated by the caprylic acid treatment, and parvovirus B19 was effectively removed in the polyethylene glycol precipitation and nanofiltration stages, the total reduction of parvovirus being ≈ 14 log10.
Conclusions The new process gives pure and stable IgG solution with an average yield of 4·8 g of IgG per kg of recovered plasma and has a very high capacity to remove even physico-chemically resistant viruses.