Prion removal effect of a specific affinity ligand introduced into the manufacturing process of the pharmaceutical quality solvent/detergent (S/D)‐treated plasma OctaplasLG®

Background and Objectives A new chromatographic step for the selective binding of abnormal prion protein (PrP Sc ) was developed, and optimization for PrP Sc capture was achieved by binding to an affinity ligand attached to synthetic resin particles. This step was implemented into the manufacturing process of the solvent/detergent (S/D)‐treated biopharmaceutical quality plasma Octaplas ® to further improve the safety margin in terms of risk for variant Creutzfeldt–Jakob disease (vCJD) transmission. Materials and Methods Intermediates and Octaplas ® final container material, spiked with hamster brain‐derived PrP Sc ‐containing fractions, were used for experiments to establish the feasibility of introducing this novel chromatography step. The binding capacity per millilitre of ligand gel was determined under the selected manufacturing conditions. In addition, the specificity of the ligand gel to bind PrP Sc from human sources was investigated. A validated Western blot test was used for the identification and quantification of PrP Sc . Results A reduction factor of ≥ 3·0 log 10 could be demonstrated by Western blotting, utilizing the relevant Octaplas ® matrix from manufacturing. In this particular cell‐free plasma solution, the PrP Sc binding capacity of the selected gel was very high (≥ 6 log 10 ID 50 /ml, equivalent to roughly 10 log 10 ID 50 /column at manufacturing scale). The gel binds specifically PrP Sc from both animal (hamster and mouse) and human (sporadic and variant CJD) sources. Conclusion This new single‐use, disposable PrP Sc ‐harvesting gel ensures a very high capacity in terms of removing the pathogenic agent causing vCJD from the new generation OctaplasLG ® , in the event that prions can be found in plasma from donors incubating the disease and thereby contaminating the raw material plasma used for manufacturing.