Local tolerance and stability up to 24 months of a new 20% proline-stabilized polyclonal immunoglobulin for subcutaneous administration.
Subcutaneous administration of human IgG is an alternative to intravenous replacement therapy that is associated with more stable serum IgG levels and fewer systemic adverse events. Highly concentrated IgG solutions are most convenient to minimize infusion volume, but their preparation and stability presents substantial technical difficulties. We report on the stability and local tolerance of IgPro20, an l-proline-stabilized, 20% polyvalent human IgG developed for subcutaneous administration. Stability was tested according to ICH guidelines. Local tolerance and vasoactivity were examined in rabbit and rat models, respectively. The presence of l-proline in IgPro20 reduced viscosity and addition of Polysorbate 80 and inert gassing improved the appearance of the solution. After storage at 25 °C for 24 months, monomer + dimer content, aggregates, and fragments were within specification (≥ 90.0%, ≤ 4.0%, and ≤ 10.0%, respectively), and Fc function and antibody activities were maintained. In rats, intravenous injection of IgPro20 produced mild and transient hypotension comparable to that seen with intravenous IgG products. Local tolerance of IgPro20 in rabbits was comparable to that of a marketed subcutaneous IgG, Beriglobin P. Functionality and quality of IgPro20 are maintained during storage at 25 °C for at least 24 months. The product is well tolerated as assessed in animal models.
CSL Behring AG, Wankdorfstrasse 10, 3000 Berne 22, Switzerland. werner.maeder@cslbehring.com
Werner
W
Maeder
Patricia
P
Lieby
Andrea
A
Sebald
Martin
M
Spycher
Renzo
R
Pedrussio
Reinhard
R
Bolli
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004487:Edema / Q000139:chemically induced; D004890:Erythema / Q000139:chemically induced; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007124:Immunoenzyme Techniques; D007141:Immunoglobulin Fc Fragments / Q000032:analysis; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D010146:Pain / Q000139:chemically induced; D011392:Proline / Q000737:chemistry*; D055503:Protein Multimerization; D011817:Rabbits; D051381:Rats; D013053:Spectrophotometry; D013696:Temperature; D013997:Time Factors
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011392:Proline