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Biochemical comparison of four commercially available C 1 esterase inhibitor concentrates for treatment of hereditary angioedema
Author(s) -
Feussner Annette,
Kalina Uwe,
Hofmann Peter,
Machnig Thomas,
Henkel Georg
Publication year - 2014
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12678
Subject(s) - hereditary angioedema , chemistry , chromatography , nephelometry , angioedema , esterase , enzyme , antibody , biochemistry , immunology , medicine
Background For safe and efficacious treatment of hereditary angioedema, C 1 esterase inhibitor ( C 1‐ INH ) concentrates should have high purity and high amounts of functional protein. As no pharmacopoeia requirements exist for C 1‐ INH concentrate lot release, biochemical characteristics as declared by the manufacturers may not be compared directly. This study compared the characteristics and purity profiles of four commercially available C 1‐ INH concentrates. Study Design and Methods The analysis included one transgenic ( R uconest) and three plasma‐derived ( B erinert, C etor, C inryze) C 1‐ INH concentrates. C 1‐ INH antigen concentration was determined by nephelometry, total protein (specific activity) with a B radford assay, purity by size‐exclusion chromatography and gel electrophoresis, and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry was performed. Results Functionality (inversely proportional to antigen‐to‐activity ratio) was lowest for R uconest (1.67), followed by C etor (1.42), B erinert (1.24), and C inryze (1.22). Specific activity (U/mg) and purity (%) were highest in R uconest (12.13; 98.6) and B erinert (11.57; 97.0), followed by C inryze (10.41; 89.5) and C etor (9.01; 88.6). Main protein bands were found for all plasma‐derived products at approximately 105 kDa, and for R uconest, at approximately 98 kDa. Additional bands in the plasma‐derived products were α1‐antichymotrypsin, ceruloplasmin, F actor C 3 ( C inryze/ C etor), and immunoglobulin heavy constant mu ( B erinert). Conclusion R uconest has a very high purity profile but is not identical to the human C 1‐ INH protein. Of the plasma‐derived products, Berinert has the highest purity profile. The impact of the nontherapeutic proteins identified has not yet been evaluated. For harmonization of the analysis for drug release, we recommend the establishment of regulatory requirements for purity determination and the implementation of threshold levels in C 1‐ INH concentrates.