Original zyxwvu Papers zyxwv Vox Sang 1989;57:4-9 zyxwvutsrqpo 0 1989 S. Karger AG. Basel W42-9CO7/89/05714Jl4 $2.75/0 Effects of Plasma Collection Systems zyx and Processing Parameters on the Quality of Factor IX Concentrate' zyxw A. Farrugia, D . Spiers, I. Young, A. Oates, R. Herrington, E Damianos Blood Products Development Group, Blood Products Division, Commonwealth Serum Laboratories, Parkville, Victoria, Australia Abstract. Using pilot-scale production of our present factor IX (I1 and X) concentrate, we have studied the effects of starting plasma source and processing parameter on two in-vitro indicators of product quality zyx - yield and thrombogenic potential. Plasma source did not affect factor IX yield but had a marked effect on thrombogenic potential. Factor IX concentrates produced from plasma derived through centrifugation-based technology showed significantly higher throm- bogenic potential than products derived from plasma derived through a filtration-based system. Removal of Cohn fraction I prior to ion-exchange chromatography resulted in a drop in factor IX yield and thrombogenic potential, as did heat treatment to 80°C for 72 h. We conclude that a membrane-filtration-based plasmapheresis system may be the preferred method of plasma procurement for factor IX concentrate production. Introduction The collection of source plasma for coagulation factor concentrate production may be expected to grow in the near future, as the need to manufacture purer and safer products results in an increasing demand for raw material. The main driving force behind this developement is bound to be factor VIII, where severe sterilization protocols to inactivate contaminating viruses may impose a severe yield penalty. Recent findings suggest that (low-yielding) ultra- purification methods may result in less immunosuppressive products [l] but may also be expected to increase the de- mand for starting plasma. This continuing demand for coagulation factor concen- trates is leading volunteer-based blood transfusion services to examine plasmapheresis as a means of obtaining source material. Although plasma recovered through red cell har- vesting has traditionally been the main source material supplied by these services to their fractionation facilities, several developments, e.g. the need to subject products to yield-reducing viral sterilization procedures, have led to plasmapheresis becoming the only means to collect suffi- cient plasma if overcollection and wastage of red cells is to ' The data published in this paper were presented in part at the Congress of the International Society for Blood Transfusion, London, July 1988. be avoided [2]. A number of studies [3-51 have described technical aspects of plasma production using different plas- mapheresis systems, but published information on the qual- ity of the resulting coagulation factor products is scanty and mostly limited to factor VIII [6,7]. However, one report [8] describes the use of a centrifugal plasmapheresis system in deriving a factor IX concentrate; concern was expressed because the product exhibited high in vitro thrombogenic- ity, a recognized hazard in these products [9]. The possibility that source material derived by automat- ed plasmapheresis would result in unsatisfactory factor IX concentrate was of concern to our laboratories, where large amounts of this product are produced for a variety of in- dications. We therefore prepared factor IX concentrates from different types of starting plasma and studied these to show whether source type affected the quality of the prod- uct. We also took the opportunity to examine whether elimination of our current practice of removing Cohn frac- tion I was possible without affecting the quality of our product and whether heat treatment to 80°C could be in- corporated into our present process. Materials and Methods Plasma was supplied to our department by the Blood Processing Department of the Red Cross Blood Bank, South Melbourne, Victoria. We studied material derived from 3 sources: