The studies confirmed that the affinity ligand chromatography under the developed conditions can be introduced into the Octaplas manufacturing process, as a mean to reduce potentially present PrP(Sc), without hampering the proven quality of this product.

No abstract

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.

BACKGROUND Plasma stored refrigerated for up to 5 days after thawing is common practice in many US hospitals. Therefore, clotting factor activities in fresh‐frozen plasma (FFP), plasma frozen within 24 hours (PF24), and solvent/detergent‐treated plasma (SDP), thawed and stored at 1 to 6°C for up to 5 days, were investigated. STUDY DESIGN AND METHODS Five A, B, O, and AB units of FFP, PF24, and SDP were thawed and maintained for 5 days at 1 to 6°C. The activity of factor (F)V, FVII, FVIII, protein S (PS), and ADAMTS13 was determined in each unit at baseline and every 24 hours thereafter for 5 days. RESULTS After thaw, mean values of the variables tested were within the normal range in all three plasma products although, in SDP, FVIII activity was significantly lower (p = 0.0039). After 5 days of storage all factors significantly declined except for ADAMTS13 activity, which was stable. Mean FVIII and ADAMTS13 activity was comparable in all three plasma products and within the normal range, mean FV activity was significantly lower in FFP and PF24 (p<0.0001) compared to SDP, and mean FVII activity was significantly lower in PF24 (p<0.03) than in FFP or SDP. Mean PS activity was below the normal range in all three plasma products with the lowest values in SDP (p = 0.0001). CONCLUSION Over 5 days of refrigerated storage the changes in the measured coagulation factors in FFP, PF24, and SDP are comparable. Clinical follow‐up is needed to assess whether slightly lower PS levels in SDP are clinically important.

Purpose: This study summarizes the characteristics and virus safety profile of Wilate®, a new human plasma-derived, high purity, double virus inactivated VWF/FVIII concentrate. The manufacturing process comprises two chromatographic steps, ensuring high purity and preserving the integrity and functionality of the VWF/FVIII complex. The optimised solvent/detergent treatment (S/D) and terminal dry-heat treatment (PermaHeat) of the lyophilised product provide two effective and robust virus inactivation steps for enveloped (EV) and one step for non-enveloped viruses (NEV). Methods: Functional and structural properties of the VWF/FVIII concentrate were studied utilising state-of-the-art assays. The reduction factors for a panel of model viruses were determined in down-scale experiments valid for the respective manufacturing steps. Summary of results: The integrity of the VWF/FVIII concentrate was confirmed by all tests. The ratio between VWF:RCo and FVIII:C was close to that in plasma of blood donors. The VWF multimeric profile demonstrated >10 bands in all batches and the triplet structure was very well preserved. A high specific activity, on average 122 IU FVIII:C/mg total protein, was measured in 15 batches recently produced. SE–HPLC revealed a one-peak-product, representing the VWF/FVIII-complex. All viruses tested were rapidly inactivated by at least 4 log10. The PermaHeat treatment of the lyophilised product at +100°C for 2 hours, at a specified residual moisture of 0.7–1.6%, was efficient for the inactivation of both EV and NEV. Conclusion: Wilate® is a high purity, double virus inactivated concentrate containing functional VWF and FVIII in a ratio close to plasma of healthy subjects. The product has an excellent viral safety profile. The safe and effective treatment of patients with von Willebrand disease and haemophilia A was demonstrated in multiple clinical trials.