The past, present and future of blood plasma fractionation

The lead author, John Curling, was inspired by a visit to Kabi (now Octapharma) in Stockholm in early 1970 to engage himself in the development of plasma fractionation technology. He formed a small process development group at Pharmacia (now Cytiva) in Sweden to explore chromatographic alternatives to Cohn fractionation. After pilot plant studies were conducted in Helsinki in collaboration with the Finnish Red Cross Fractionation Centre, first results of alcohol-free, chromatographic fractionation were presented at an NIH meeting in 1977. A method for albumin production was adopted by Transfusion Centres in Europe and elsewhere and early in 1990 the technology was adopted by CSL Behring and extended to IgG at full industrial scale confirming the applicability in commercial fractionation and foretelling the ubiquitous use of chromatographic unit operations in plasma product purification. In 1989, he was the lead for the Swedish Government supported establishment of the National Plasma Fractionation Centre in India and was a Temporary WHO advisor to Nepal and Myanamar.

John Curling

After consulting on the purification of plasma proteins expressed in caprine milk he became involved in the development of affinity methods of fractionation using synthetic ligands. He has been chairman of the Recovery of Biological Products Conference Series (ACS-BIOT) and a frequent chair/speaker at plasma conferences. He is the co-editor/author of Methods of Plasma Protein Fractionation (Academic Press 1980) and Production of Plasma Proteins for Therapeutic Use (Wiley 2013). After more than 50 years immersed in plasma fractionation and extensive travel, his interest and contribution to the field continues. He enjoys art and music and spends time at his retreat on the Baltic coast but could not refuse the proposal from Albert Farrugia to, again, write about the technological development of blood plasma fractionation and opportunities presented by new innovations.

“When considering content of the article, I thought that both national bodies looking to increase access to PDMPs potentially by local fractionation and established fractionators needing to increase capacity face difficult decisions on the choice of production technology. It is a long and risky road from concept to approved product using a disruptive and unproven technology and a significant time frame for a new build. So, which technology? There is not a simple answer. Cohn’s work is superbly researched and he learnt from Nobel Laureates as did the pioneers of chromatographic purification much later. I felt that this, often poorly understood, intensely scientific basis of plasma fractionation that spans eight decades, deserved fresh commentary and acknowledgement, providing insight for researchers, process engineers and decision makers and enthusiasm for further innovation. I trust we have achieved our goals.”

The initiator and driver behind this article is Prof. Albert Farrugia. During his forty-five year career in the blood and plasma sector, Albert has contributed to product development, regulatory affairs and strategic policy in blood and plasma collection agencies, government bodies and commercial organisations globally. He has served on a wide range of international bodies, including the US and European Pharmacopeia Commissions, the World Health Organisation, the World Federation of Haemophilia, the American Association of Blood Banks and the International Society for Blood Transfusion. He has held a number of academic positions and is currently adjunct Professor in the Faculty of Health and Medical Sciences in the University of Western Australia. He has authored or co-authored ca 200 contributions to the international medical and scientific literature, including 160 listings in PubMed, the internationally recognized data base for the peer-reviewed medical literature. He is a passionate advocate for the community of patients with rare disorders, of which he is also a member, and serves on the advisory board of three patient organisations on a voluntary basis.

Prof. Albert Farrugia

As he eases himself into retirement, Albert enjoys painting, literature and music, has co-published two books of Haiku poetry, and is a renowned philatelist with successful contributions to international competitions. He divides his time between the Apennine mountains of Northern Tuscany and St Kilda in Melbourne. In 2009, he was awarded the Ruth Sanger Oration Medal by the Australia and New Zealand Society for Blood Transfusion.

“I developed an interest in generating this project after a long period of hearing the founders of plasma fractionation industry being denigrated by a number of ambitious adventurers who frequently refer to Cohn fractionation as “bucket chemistry ” with no innovative effort since its inception, in order to tout alternatives which have foundered before seeing the light of day. I suspect that members of the IPFA Board may have had similar experiences. In addition, I wanted to elicit the thoughts and harness the expertise of the two other authors on this paper, whose experience and knowledge in the field of fractionation are vast and should be shared in an accessible fashion. In this paper, the industry’s history is reviewed, alternative technologies are assessed, and areas such as disruptive therapies and pathogen reduction are discussed. We believe that our aim in sharing our experience has been met, and we encourage dissemination of this work as a route to a higher understanding of this complex sector.”

Dr. Leni von Bonsdorff is since 2020 the Executive Director of the International Plasma and Fractionation Association (IPFA). She has over 30 years’ experience of plasma-derived medicinal products and has held executive positions at Sanquin in Finland and worked within R&D at the Finnish Red Cross Blood Service.

Her experience ranges from R&D, production, and clinical use to marketing and sales of plasma products, including arrangements for product tender agreements and reimbursements within the Finnish health care system. She has published several articles in the field, and her PhD studies were related to a method to produce and study clinically a novel plasma product apotransferrin for iron binding therapy. In recent years she was the chairman of the Swedish Academy of Engineering Sciences in Finland and board member at the Technology Academy Finland that awards technological innovations for a better life with the Millennium Technology Prize. She balances her passion for plasma products with family life and a growing number of grandchildren and will enjoy her summer vacation in the Finnish archipelago in her garden with a good book and a knitting project close by.

Dr. Leni von Bonsdorff

“I express my deep gratitude to both John and Albert for their hard work and willingness to share their knowledge in this way, and for the very rewarding collaboration during the writing process. Since IPFA was founded in 1990, our association has been involved in the science of plasma fractionation and safety of plasma derived medicines for 35 years of the over 80 year journey. We are extremely proud to be contributing to this area with a new updated oversight.

My personal experience in this field encompasses the same period as IPFA has existed, and when I started, there were those who said plasma products will be replaced by recombinants. As we know now, this is clearly not the case, instead the need for the products is still growing with new indications and inclusion of more patients. The plasma fractionation and the plasma products therapies deserve to be in focus for scientists, and all involved in developing better processes and new or better products for patients worldwide. I hope this article will be seen as a useful resource for that purpose.”