Intravenous Immunoglobulin (IVIG) is a complex blood product derived from human plasma. This therapy, composed of concentrated antibodies, provides support for individuals with compromised immune systems or certain autoimmune conditions. Its manufacturing involves carefully controlled steps, transforming donated plasma into a highly purified therapeutic agent.
Understanding IVIG
Intravenous Immunoglobulin (IVIG) is a preparation of pooled and purified antibodies, primarily immunoglobulin G (IgG), sourced from the plasma of thousands of healthy human donors. These antibodies are a part of the body’s immune system, identifying and neutralizing foreign invaders like bacteria and viruses. IVIG therapy treats immune deficiencies, where the body cannot produce enough antibodies, and autoimmune disorders where the immune system attacks healthy tissues. Its application stems from its ability to modulate immune responses, replace missing antibodies, and offer protection against infections while reducing inflammation.
Sourcing and Initial Plasma Preparation
The journey of IVIG begins with rigorous plasma donation from thousands of healthy individuals. Donors undergo comprehensive screening, including health checks, medical history review, and testing for transmissible viruses like HIV and hepatitis. Donors must meet specific age and weight requirements. Plasma is collected through plasmapheresis, where whole blood is drawn, plasma is separated, and remaining blood components are returned to the donor. Individual donations are then pooled and tested before entering the manufacturing stream.
Fractionation and Purification Steps
The core of IVIG manufacturing involves separating and purifying immunoglobulin G from the pooled plasma. This process commonly employs Cohn cold ethanol fractionation. This method leverages varying solubility of plasma proteins at different ethanol concentrations and temperatures to precipitate specific protein fractions. The goal is to isolate Fraction II, rich in IgG, while removing other plasma proteins.
Following initial fractionation, additional purification steps enhance IgG purity and concentration. Chromatography, particularly ion-exchange chromatography, plays a role in this stage. This technique separates proteins based on their charge, effectively removing impurities such as immunoglobulin A (IgA), immunoglobulin M (IgM), and pro-coagulant factors. Some modern processes also utilize affinity chromatography, which can directly capture IgG or recover it from side fractions, streamlining purification and improving yield. These steps ensure the final product contains over 95% unmodified IgG for its therapeutic function.
Ensuring Product Safety and Quality
Manufacturers incorporate multiple viral inactivation and removal steps to eliminate potential viral contaminants. Common methods include solvent/detergent (S/D) treatment, which disrupts viral lipid envelopes, and pasteurization, involving heat treatment at 60°C for 10 hours, to inactivate viruses. Low pH incubation, often at a pH around 4, effectively inactivates enveloped and some non-enveloped viruses by altering their structure. Nanofiltration provides a physical barrier, using membranes with pores as small as 20 to 35 nanometers to remove viruses based on size, allowing smaller IgG molecules to pass through while retaining larger viral particles. Throughout the entire manufacturing process, extensive quality control testing is performed at various stages, including checks for purity, potency, and sterility, to ensure the final IVIG product meets stringent regulatory standards.
Finalizing and Distributing IVIG
After purification and safety measures, IVIG undergoes final formulation, involving the addition of stabilizers to maintain protein integrity and extend shelf life. The IVIG solution is then aseptically filled into vials or bottles, ensuring a sterile environment to prevent contamination. These containers are packaged, labeled with information, and prepared for distribution. Storage conditions vary by brand, with some formulations requiring refrigeration (2-8°C) and others stable at room temperature (up to 25°C). The completed IVIG products are then distributed to healthcare providers globally for patient administration.