Flebogamma 5 Human Normal Immunoglobulin for Intravenous Administration

® Flebogamma 5% Human Normal Immunoglobulin for Intravenous Administration Pure Confidence Flebogamma® 5% Pure Confidence

Flebogamma® 5%: Plasma Safety • Grifols monitors the entire plasma production process from start to finish. All Grifols products are subjected to rigorous donor screening, testing and viral elimination (inactivation and removal) processes to enhance their quality and safety. • Grifols has been awarded the Quality Standards of Excellence Assurance and Leadership (QSEAL) by the Plasma Protein Therapeutics Association (PPTA). Flebogamma® 5% Pure Confidence

Flebogamma® 5%: Processing plasma • More than 10 years of experience and know-how 4 1 2 5 3 8 6 7 15 10 9 11 12 13 14 16 17 18 19 20 21 1 - Frozen Plasma 7 - Fraction II + III Precipitate 14 - Centrifugation & Filtration 2 – Thawing & Centrifugation 8 - Supernatant 15 - Supernatant 9 - Centrifugation & Filtration 16 – DEAE - Sephadex Chromatography 3 - Cryoprecipitate 4 – Cryoprecipitate-Poor Plasma 5 - Cold Ethanol Fractionation 6 - Centrifugation & *Viral elimination methods Filtration Flebogamma® 5% 10 -Precipitate 11 - Stabilization with DSorbitol 17 - Concentration and p. H Adjustment 12 - Pasteurization (60 o. C, 10 hours)* 18 - Centrifugation & Filtration 13 - PEG Precipitation* 20 - QC Testing Quarantine 19 - Sterile Filtrations 21 - Flebogamma® 5% Pure Confidence

Flebogamma® 5%: Viral Safety Flebogamma® 5% was one of the first liquid immune globulins products to incorporate pasteurization as a viral inactivation method. Pasteurization has been validated to achieve significant inactivation of both enveloped and nonenveloped viruses. Grifols developed a method of pasteurization (heat treatment at 60ºC 10 h) using sorbitol as a stabilizer, which avoids denaturalization of proteins and preserves antibody activity. Flebogamma® 5% Pure Confidence

Flebogamma® 5%: Pure Confidence High Purity Ig purity: 99. 37% ± 0. 26 (n= 220 consecutive lots) Flebogamma® 5% Pure Confidence

Flebogamma® 5%: Pure Confidence High Purity Monomers + Dimers content: > 99. 9% (n= 220 consecutive lots) Flebogamma® 5% Pure Confidence

Flebogamma® 5%: Pure Confidence High Purity Fragments: Not detectable (n= 220 consecutive lots) Flebogamma® 5% Pure Confidence

Flebogamma® 5%: Pure Confidence High Tolerability Ig. A content: 0. 011 ± 0. 003 mg/ml (n= 220 consecutive lots) Flebogamma® 5% Pure Confidence

Flebogamma® 5%: Pure Confidence High Tolerability Anticomplementary Activity: 0. 27 ± 0. 06 CH 50/mg. Ig (n= 220 consecutive lots) Flebogamma® 5% Pure Confidence

Flebogamma® 5%: Pure Confidence High Tolerability Pre-kallikrein Activator: <2 I. U. (n= 220 consecutive lots) Flebogamma® 5% Pure Confidence

Flebogamma® 5%: Pure Confidence Physiologic Isotonic solution: 328. 6 ± 0. 26 m. Osm/Kg (n= 220 consecutive lots) Flebogamma® 5% Pure Confidence

Flebogamma® 5%: Pure Confidence Physiologic Normal p. H: 5. 60 ± 0. 07 (n= 220 consecutive lots) Flebogamma® 5% Pure Confidence