Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries

Abstract

Plasma-derived immunoglobulin G (IgG) is on WHO’s Essential Medicines List, yet developing countries face severe shortages of this critical treatment. Infusion of IgG prepared from locally-collected plasma provides an advantageous mix of antibodies to viral and bacterial pathogens found in the living environment, and this can reduce recurrent infections in immune-deficient patients. We developed a simple manufacturing process using disposable equipment (blood bags, hemodialyzer, and filters) to isolate immunoglobulins from minipools of 20 plasma donations. This process yields a ca. 90% pure virally-inactivated immunoglobulin fraction at 50–60% recovery. Anti-hepatitis B and anti-rubella immunoglobulins were enriched fourfold to sixfold. The product was free of in-vitro thrombogenic and proteolytic activity, confirming its expected clinical safety profile. Virus validations showed caprylic acid treatment robustly inactivated or removed infectivity of lipid-enveloped viruses, including human immunodeficiency virus (HIV) and hepatitis C virus model. This simple and cost-effective process is implemented in Egypt to prepare experimental batches for clinical evaluation. It can enhance immunoglobulin supplies to treat immunodeficient patients through passive transmission of antibodies directed against local pathogens. The method requires minimal training and reasonable infrastructure, and is a practical means to prepare convalescent hyperimmune IgG during infectious outbreaks such as the current Ebola episode.