Humoral immunodeficiency patients require immunoglobulin replacement to prevent infection. Traditional intravenous immunoglobulin manufacturing methods have had the potential for containing impurities caused by physical, chemical and thermal stressors that alter proteins. Two intravenous immunoglobulin products, BIVIGAM® and ASCENIV™, are manufactured by a modified Cohn-Oncley fractionation method followed by chromatographic purification. These products have undergone a systematic quality by design optimization to identify critical manufacturing processes to produce the highest quality product. This data driven, small-scale approach has led to manufacturing enhancements that have yielded consistent product improvements. The systematic approach to optimizing manufacturing has guided process changes, in-process, procedural and engineering controls that have reduced protein shearing and aggregation, and improved purity resulting in products with lot-to-lot consistency.
Keywords: ADMA; ASCENIV; BIVIGAM; IVIG; PIDD; RI-002; immunoglobulin; manufacture; optimization; primary immune deficiency disease.