Building and operating a plasma splitting facility is a very complex task, especially in countries that do not yet have mastered this technology. Even the decision to carry out such a facility is complex and is criticized, sometimes in a rather virulent way, political, economic and technological. In accordance with Decree-Law No. 261 of 20 December 2007, the Ministry of Health, in agreement with the autonomous regions and provinces, defines, on the basis of information provided by the Italian National Blood Centre, a programme to ensure both the development of plasma collection and the promotion of rational and appropriate use of PPIs. The ministerial decree of 2 December 2016 contains the first programme ever published in Italy to monitor national self-sufficiency in plasma and PDMP. It sets out the strategic principles and objectives at the national and regional levels to be achieved over the 2016-2020 period. Industrial yields for albumin and IVIG are approximately 25.2 and 3.6 grams (g) per kg of plasma, respectively, regardless of plasma category. On the contrary, yields for pdFVIII, pdFIX, PCCs and AT are strongly influenced by the quality of plasma sent for splitting by each regional blood transfusion service. In addition, it is important to highlight the risk associated with the increase in the share of the toll fraction against market share. Potential PMPs suppliers would be discouraged from remaining in the market and there could be a reduction or even a complete lack of product availability in the event of a shortage. In addition, the national plasma comes from voluntary, regular, responsible, anonymous and free-to-do donations2. Autonomous regions and provinces (therefore referred to as „regions“) send plasma collected by blood establishments (BE) individually or in association with Kedrion Biopharma (Kedrion SpA, Castelvecchio Pascoli, Lucca, Italy), which is currently the only producer authorized under a toll splitting agreement. The latter has the ability to produce at least the following PMPs: human albumin solution (albumin), multipurpose immunoglobulin (for intravascular administration, IVIG), plasma-derived factor VIII concentrates (pdFVIII), plasma-derived factor IX concentrates (pdFIX), prothrombin (PC) and antithrombin complexes (AT).

However, the regions still own plasma sent for splitting, PMPs produced and residual raw materials, including releases. National Plasma and PDPS Systems Regions, individually or in a consortium, make available to manufacturers covered in the ministerial decree of 5 December 2014 the plasma collected in blood establishments and collection centres. Regions recover finished products on the basis of specific toll-splitting agreements and contracts. Technology transfer is always a very difficult and tense process; However, we still believe that this is the easiest and fastest way to maintain plasma splitting technology. The coupling of the implementation of the plasma splitting facility with a fractionation of tolls, necessarily with the same foreign company, is an option that can greatly facilitate the development of the project. This strategy allows the team to stay in the dough very quickly and to launch several activities much earlier (10). The way forward should be the requirement for bioequivalence studies for technology transfer situations.