Plasma-derived industry and plasma-derived medicinal products in the Italian National Blood Transfusion Service.

The priority objectives of the Italian Transfusion System are self-sufficiency for blood components and for plasma-derived products. Currently the collection activity guarantees self-sufficiency of blood components, including plasma for clinical use, but not for plasma-derived drugs, ie albumin and immunoglobulins in particular. The National Plasma Program of 2016-2020, issued a Ministerial Decree on December, 2, 2016, aims to achieve this goal, both by increasing the collection of plasma and therefore its transfer to plasma derivation companies, and by increasing the appropriateness of the requests. Currently, the companies Grifols SpA, Kedrion SpA, CSL Behring, and Baxter-Baxalta Srl are present on the Italian market, individually or in business associations, with which the various Italian regions have established an agreement based on the national legislation.

Trends in Plasma Toll Fractionation for Self Sufficiency of Plasma-Derived Medicinal Products in Italy.

BACKGROUND AND AIMS: In Italy, domestic plasma toll fractionation, performed until 2014 by only one company, had limited access to different technologies and products and to price competition. In 2017, four companies acted as competitive toll fractionators for 827,720 kg of plasma. Here, we evaluate the contribution of toll manufacturing and the effects of competition on national self-sufficiency. RESULTS: An increase in immunoglobulin production is granted by new fractionators (11-41%, in some regions adequate for self-sufficiency), although the rise in demand will still require market contribution. The decrease in albumin use (-2.6% in 2015 vs. 2014) is probably due to a better control of an impressively high demand (35.4 t in 2015). Factor VIII demand is still higher than production, but domestic plasma cannot serve as its unique source. New tenders enlarged the portfolio of products and a theoretical self-sufficiency is granted for Factor IX, prothrombin complex concentrates, antithrombin, fibrinogen, and alpha-1-antithrypsin. CONCLUSIONS: Competition among companies resulted in higher yields of albumin and immunoglobulin, decreasing their level of market dependence, an increase in the portfolio of medicines, and a decrease in price due to fractionation (20-30%), thus improving perspectives of the national program for self-sufficiency in plasma-derived medicinal products.

IgG Antibody Responses to the Aedes albopictus 34k2 Salivary Protein as Novel Candidate Marker of Human Exposure to the Tiger Mosquito.

Mosquitoes of the Aedes genus transmit arboviruses of great importance to human health as dengue, chikungunya, Zika and yellow fever. The tiger mosquito Aedes albopictus can play an important role as arboviral vector, especially when Aedes aegypti is absent or present at low levels. Remarkably, the rapid worldwide spreading of the tiger mosquito is expanding the risk of arboviral transmission also to temperate areas, and the autochthonous cases of chikungunya, dengue and Zika in Europe emphasize the need for improved monitoring and control. Proteomic and transcriptomic studies on blood feeding arthropod salivary proteins paved the way toward the exploitation of genus-specific mosquito salivary proteins for the development of novel tools to evaluate human exposure to mosquito bites. We previously found that the culicine-specific 34k2 salivary protein from Ae. albopictus (al34k2) evokes specific IgG responses in experimentally exposed mice, and provided preliminary evidence of its immunogenicity to humans. In this study we measured IgG responses to al34k2 and to Ae. albopictus salivary gland protein extracts (SGE) in individuals naturally exposed to the tiger mosquito. Sera were collected in two areas of Northeast Italy (Padova and Belluno) during two different time periods: at the end of the low- and shortly after the high-density mosquito seasons. Anti-SGE and anti-al34k2 IgG levels increased after the summer period of exposure to mosquito bites and were higher in Padova as compared to Belluno. An age-dependent decrease of anti-saliva IgG responses was found especially in Padova, an area with at least 25 years history of Ae. albopictus colonization. Moreover, a weak correlation between anti-saliva IgG levels and individual perception of mosquito bites by study participants was found. Finally, determination of anti-al34k2 IgG1 and IgG4 levels indicated a large predominance of IgG1 antibodies. Overall, this study provides a convincing indication that antibody responses to al34k2 may be regarded as a reliable candidate marker to detect temporal and/or spatial variation of human exposure to Ae. albopictus; a serological tool of this kind may prove useful both for epidemiological studies and to estimate the effectiveness of anti-vectorial measures.

Quality control of recovered plasma for fractionation: an extensive Italian study.

BACKGROUND: This study was aimed at obtaining significant information on the quality of whole-blood plasma (WBP) delivered to a private pharmaceutical company by the blood transfusion centers (BTCs) of 10 Italian regions. STUDY DESIGN AND METHODS: A statistical sampling plan of plasma units took into account the contribution each selected blood transfusion center, belonging to the 10 regions, made to the plasma pool annually delivered to the pharmaceutical company. A total of 1787 plasma units were selected for coagulation Factor VIII (FVIII:C) and Factor VIII antigen (FVIII:Ag) analysis. RESULTS: The FVIII:C mean value was 0.99 IU per mL; it was significantly lower in O units (0.86 IU/mL) than in non-O units (1.08 IU/mL). The mean value of FVIII:Ag was 0.90 IU per mL; it was significantly lower in O units (0.78 IU/mL) than in non-O units (0.99 IU/mL). In units with a FVIII:C level of less than 0.70 IU per mL, the FVIII:Ag mean value (0.62 IU/mL) was higher in comparison to the FVIII:C mean value (0.57 IU/mL). Instead, in the units with a FVIII:C level of at least 0.70 IU per mL, the mean level of FVIII:C (1.08 IU/mL) was higher than that of FVIII:Ag (0.96 IU/mL). CONCLUSIONS: The mean value of FVIII:C (0.99 IU/mL) in whole-blood plasma produced by the 10 Italian regions is higher than that reported in other studies. A total of 83.1 percent of units have a FVIII:C level of at least 0.70 IU per mL. The mean level of FVIII:Ag is lower than that of FVIII:C. FVIII:Ag is higher in those units with a FVIII:C level of less than 0.70 IU per mL, while it gradually decreases as FVIII:C exceeds 0.70 IU per mL, thus showing a greater resistance to handling of plasma in the production steps mostly affecting FVIII:C stability.