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

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 non-enveloped 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 High Purity Ig purity: 99.37% ± 0.26 (n= 220 consecutive lots)

Flebogamma® 5%: Pure Confidence High Purity Monomers + Dimers content: > 99.9% (n= 220 consecutive lots)

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

Flebogamma® 5%: Pure Confidence High Tolerability IgA content: 0.011 ± 0.003 mg/ml (n= 220 consecutive lots)

Flebogamma® 5%: Pure Confidence High Tolerability Anticomplementary Activity: 0.27 ± 0.06 CH50/mgIg (n= 220 consecutive lots)

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

Flebogamma® 5%: Pure Confidence Physiologic Isotonic solution: 328.6 ± 0.26 mOsm/Kg (n= 220 consecutive lots)

Flebogamma® 5%: Pure Confidence Physiologic Normal pH: 5.60 ± 0.07 (n= 220 consecutive lots)