Intravenous Immunoglobulin Production: From Plasma to Life-Saving Therapy
IVIG production transforms human plasma into concentrated therapeutic products through a sophisticated, multi-stage process. This essential therapy depends on rigorous quality standards and advanced bioprocessing technologies to ensure safety and efficacy for patients worldwide.
Plasma Collection: The Foundation of IVIG
Donor Screening
Rigorous health checks ensure donor eligibility and screen for infectious diseases like HIV and hepatitis per FDA/EMA regulations.
Plasmapheresis
Blood is drawn, plasma separated, and cellular components returned to donors in a 45-90 minute process.
Plasma Pooling
Contributions from 1,000-10,000 donors are combined to create a diverse antibody profile, enhancing therapeutic effectiveness.
Fractionation: Separating Plasma Components
Cold Processing
Plasma is chilled to specific temperatures during processing to maintain protein integrity.
Cohn Process
Varying concentrations of ethanol, pH levels, and temperatures precipitate different protein fractions.
Fraction Isolation
Fraction II, containing the bulk of IgG antibodies, is carefully isolated for IVIG production.
Collection
Other fractions are preserved for separate therapeutic products like albumin.
Advanced Purification Techniques
Ion-Exchange Chromatography
Separates proteins based on electrical charge, allowing for precise IgG isolation and concentration while removing impurities.
Affinity Chromatography
Uses specifically designed ligands to bind target immunoglobulins, enabling isolation of particular IgG subtypes for enhanced therapeutic properties.
Ultra/Nanofiltration
Multi-stage filtration systems remove residual contaminants, lipids, and protein aggregates through progressively finer membrane systems.
Pathogen Inactivation: Ensuring Product Safety
Solvent/Detergent Treatment
Chemicals like tri-n-butyl phosphate disrupt lipid-enveloped viruses such as HIV and hepatitis C.
Heat Pasteurization
Controlled heating at 60°C for 10 hours inactivates non-enveloped viruses like hepatitis A.
Low pH Incubation
Maintaining solution at pH 4-4.5 for several hours neutralizes additional pathogens.
Nanofiltration
Removes particles as small as 15-20 nanometers, capturing remaining viruses or prions.
Formulation and Stabilization
Concentration
Purified IgG concentrated to 5-10% (50-100 g/L)
Stabilization
Addition of glycine, maltose, or other excipients
pH Adjustment
Optimized to pH 4.5-7 for stability and tolerability
Sterile Filtration
Final microbial removal before packaging
Quality Control and Packaging
Every IVIG batch undergoes extensive testing for potency, purity, and safety before distribution. Products are aseptically filled into sterile containers, labeled with batch information and expiration dates, and typically stored at 2-8°C with a 2-3 year shelf life.
Industry Leaders and Future Innovations
Leading manufacturers continue to innovate with proprietary technologies for higher yields and safety profiles. Future developments include continuous processing systems, recombinant IgG production, and enhanced purification methods to address plasma supply challenges and reduce production costs.