Preparation of commercial quantities of a hyperimmune human intravenous immunoglobulin preparation against an emerging infectious disease: the example of pandemic H1N1 influenza

BACKGROUND: The recent H1N1 pandemic provided an opportunity to conceptually assess the possibility of rapidly providing a hyperimmune human immunoglobulin (H-IVIG) to an emerging infectious disease, in useful quantities with respect to public health. Commercial-scale H-IVIG production from plasma collected from donors convalescent from or vaccinated against pandemic influenza A (H1N1) virus is described. STUDY DESIGN AND METHODS: A special protocol was implemented for the collection, processing, and shipment of plasma from previously qualified source plasma donors, self-identifying as convalescent from or vaccinated against H1N1 influenza. A licensed IVIG manufacturing process was utilized for the preparation of two commercial lots of approximately 50 kg 10% human IVIG preparation in total. The H1N1 hemagglutination inhibition and neutralization antibody titers of the resulting H-IVIG preparations were determined and compared with standard preparations. RESULTS: Twenty-six plasma collection centers participated in the protocol. Donor enrollment exceeded 300 donors per week and within 30 days of protocol deployment plasma was being collected at a rate of more than 2000 L/week. Manufacture of both H-IVIG lots was unremarkable and both lots met the requirements for commercial release and the bulk of the product was distributed in normal commercial channels. Examination of plasma pools and final IVIG product confirmed pandemic H1N1 antibody titers substantially higher than those collected before the emergence of the pandemic H1N1 virus. CONCLUSIONS: This work demonstrates the feasibility of producing a H-IVIG preparation at large scale relatively rapidly, with a significant enrichment in antibodies to the H1N1 influenza, achieved by donor self-identification.