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Characterization of a Liquid Presentation of the Alpha-1-Proteinase Inhibitor Prolastin-C®
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A1757 - Characterization of a Liquid Presentation of the Alpha-1-Proteinase Inhibitor Prolastin-C®
Author Block: M. Cruz, J. Lang, K. Merritt, K. Wee, T. Willis; Grifols, Research Triangle Park, NC, United States.
Rationale: Alpha-1-antitrypsin deficiency (AATD) is a genetic condition characterized by low serum AAT levels and increased risk of emphysema. PROLASTIN®-C is an approved human-plasma derived lyophilized formulation of alpha1-PI used for chronic augmentation therapy in AATD. Grifols has recently obtained FDA approval for an alanine stabilized 5% liquid formulation as an alternate dosage form to the currently licensed lyophilized Prolastin-C. The liquid presentation retains the same desirable product quality characteristics as the lyophilized presentation, but eliminates the need for reconstitution and shortens preparation time. We report the results of an evaluation of the characterization of the 5% liquid formulation of the alpha1-proteinase inhibitor PROLASTIN-C. Methods: The objective of this study was to determine the biochemical characteristics of the Liquid Formulation of Alpha-1 Proteinase Inhibitor (Liquid A1PI) including potency, purity, protein composition, and molecular mass distribution profiles. Liquid A1PI was characterized using a panel of analytical methods consisting of antineutrophil elastase capacity, immunonephelometry, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), capillary gel electrophoresis (CGE), capillary zone electrophoresis (CZE), Western blotting, isoelectric focusing (IEF), size exclusion high-performance liquid chromatography (SEC), and mass spectrometry. Four lots of Liquid A1PI were characterized and compared to the lyophilized product. Results: Liquid A1PI had a mean functional activity of 56 mg/ml, electrophoretic purity of 97% and monomeric content of 88%. All protein levels and purity profiles, as measured by SEC, CZE and CGE and specific activity, were comparable to the lyophilized Alpha1-PI batches. Purity profiles of both the liquid and lyophilized final container materials were comparable with no additional protein impurities detected in the Liquid A1PI Lots. Soluble aggregates in liquid and lyophilized Alpha1-PI were characterized and compared for size, composition and content with comparable profiles. Conclusion: The analytical results presented serve to define the structural and functional characteristics of the 5% Liquid A1PI product with a high functional activity and high specific activity. The biochemical characterization data demonstrate that the new alanine stabilized liquid formulation contains comparable product characteristics to the lyophilized formulation of Alpha1-PI.
Author Block: M. Cruz, J. Lang, K. Merritt, K. Wee, T. Willis; Grifols, Research Triangle Park, NC, United States.
Rationale: Alpha-1-antitrypsin deficiency (AATD) is a genetic condition characterized by low serum AAT levels and increased risk of emphysema. PROLASTIN®-C is an approved human-plasma derived lyophilized formulation of alpha1-PI used for chronic augmentation therapy in AATD. Grifols has recently obtained FDA approval for an alanine stabilized 5% liquid formulation as an alternate dosage form to the currently licensed lyophilized Prolastin-C. The liquid presentation retains the same desirable product quality characteristics as the lyophilized presentation, but eliminates the need for reconstitution and shortens preparation time. We report the results of an evaluation of the characterization of the 5% liquid formulation of the alpha1-proteinase inhibitor PROLASTIN-C. Methods: The objective of this study was to determine the biochemical characteristics of the Liquid Formulation of Alpha-1 Proteinase Inhibitor (Liquid A1PI) including potency, purity, protein composition, and molecular mass distribution profiles. Liquid A1PI was characterized using a panel of analytical methods consisting of antineutrophil elastase capacity, immunonephelometry, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), capillary gel electrophoresis (CGE), capillary zone electrophoresis (CZE), Western blotting, isoelectric focusing (IEF), size exclusion high-performance liquid chromatography (SEC), and mass spectrometry. Four lots of Liquid A1PI were characterized and compared to the lyophilized product. Results: Liquid A1PI had a mean functional activity of 56 mg/ml, electrophoretic purity of 97% and monomeric content of 88%. All protein levels and purity profiles, as measured by SEC, CZE and CGE and specific activity, were comparable to the lyophilized Alpha1-PI batches. Purity profiles of both the liquid and lyophilized final container materials were comparable with no additional protein impurities detected in the Liquid A1PI Lots. Soluble aggregates in liquid and lyophilized Alpha1-PI were characterized and compared for size, composition and content with comparable profiles. Conclusion: The analytical results presented serve to define the structural and functional characteristics of the 5% Liquid A1PI product with a high functional activity and high specific activity. The biochemical characterization data demonstrate that the new alanine stabilized liquid formulation contains comparable product characteristics to the lyophilized formulation of Alpha1-PI.
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