Review The dynamics of contract plasma fractionation Albert Farrugia a, * , Daniela Scaramuccia b a School of Surgery, QEII Medical Centre, The University of Western Australia (M509), Stirling Highway, Crawley WA 6009, Australia b Value Partners Management Consulting SpA, Via Vespri Siciliani, 9, 20146, Milan, Italy article info Article history: Received 4 December 2016 Received in revised form 19 January 2017 Accepted 12 February 2017 Available online xxx Keywords: Plasma products Plasma fractionation abstract Plasma Derived Medicinal Products (PMDPs) are an essential component of the modern therapeutic armamentarium. They are differentiated from most other medicines in several ways, particularly the unique nature of the raw material used for their manufacture. Human plasma has been fractionated to PDMPs for the past 75 years, and the economics of manufacturing requires currently that as many products are harvested from each litre as is feasible and reflective of clinical needs. PDMPs may be purchased on the open market from the various commercial and not-for-profit (NFP) manufacturers. They may also be manufactured under contract (CM) from plasma supplied by government and similar agencies as a product of blood transfusion services. Clients for CM aspire to make full use of donated plasma, hence maximizing the donors' gift after the standard components of transfusion have been harvested. Many such countries also aspire to making their national clinical needs self-sufficient in PDMPs, attempting to acquire strategic independence from the vagaries of the commercial open market. The increasing commercial imperatives operating in the PMDP sector generate a tension with such ethical aspirations which are not easily resolved. In particular, the need to harvest as many proteins as possible may generate products which are surplus to national needs, necessitating an ethical paradigm for the optimal provision of such products. In addition, traditional relationships between blood services and domestic fractionation agencies may come under stress as a result of the competitive processes underpinning such transactions, which are now subject to international norms of free trade. Blood services engaged in the supply of hospital transfusion components are detached from the pharmaceutical Good Manufacturing Practices (GMP) culture needed for the production of plasma for CM, while the generation of such plasma through extraction from whole blood donations deflects the focus from that of a dedicated raw material for CM to a byproduct of the donation process. We review the field of CM, assess the current tensions within the sector, and offer suggestions for the strategic positioning of governments and other clients to ensure optimal outcomes for all the stakeholders involved. © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved. 1. Background to plasma fractionation and Plasma Derived Medicinal Products (PDMPs) Following a career in protein chemistry which saw him pur- ifying and characterizing several plasma proteins, Edwin Cohn was commissioned by the United States Navy in early World War Two to purify a stable blood substitute to treat battlefield injury [1]. Cohn's early fractionation scheme evolved from his earlier work [2] and resulted in the purification of albumin as a stable solution, clinically effective as a blood volume expander in treating acute hemorrhage. Cohn retained a high level of control over his group's work after the war, through patents which he used, not as a source of income, but as a means of controlling the quality of products produced by the nascent fractionation in- dustry [3]. Several of the companies commissioned to produce albumin during the war left the field after its end, but the origins of the current large fractionators can be traced to the companies which remain active [4]. Over the succeeding decades, this sector has grown to a global industry estimated currently at 20 billion US $ [5], extracting a range of products from a volume of 45 million litres of plasma collected globally in 2014 [5]. The initial thrust to produce albumin retained this product as the industry's staple for the first three decades following its inception, but the potential to harvest other valuable fractions enroute to albumin was recognized in Cohn's early work, and by the late 1940s he * Corresponding author. E-mail addresses: albert.farrugia@uwa.edu.au (A. Farrugia), daniela. scaramuccia@valuepartners.com (D. Scaramuccia). Contents lists available at ScienceDirect Biologicals journal homepage: www.elsevier.com/locate/biologicals http://dx.doi.org/10.1016/j.biologicals.2017.02.007 1045-1056/© 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved. Biologicals xxx (2017) 1e9 Please cite this article in press as: Farrugia A, Scaramuccia D, The dynamics of contract plasma fractionation, Biologicals (2017), http:// dx.doi.org/10.1016/j.biologicals.2017.02.007