LETTERS TO THE EDITOR Pathogen inactivation or pathogen reduction: proposal for standardization of nomenclature A look back over the table of contents of several recent issues of TRANSFUSION (e.g., May and September 2014) demonstrates an inconsistency in terminology that we believe should be addressed as more countries implement use of blood components treated to reduce the risk of blood-borne pathogen transmission. Historically the first blood derivatives that underwent some kind of treatment to decrease the risk of transmission of infectious diseases were plasma derivatives. In the early 1980s the recognition of the transmission of viral hepatitis and human immunodeficiency virus infections to patients treated with coagulation factor concentrates obtained from pooled human plasma led to the initial introduction of measures by manufacturers to inactivate the viruses potentially present in such products.1 Additional technologies were subsequently introduced; these technologies were divided into two groups: one group, called inactivation methods, destroyed the capacity of the viruses to infect the recipient using some physical or chemical techniques. The other group reduced viral infectivity through the removal of virus by nanofiltration.2 Nowadays we are facing a similar confusing situation with nomenclature related to technologies applied to labile blood components. There are several already approved in Europe for reducing pathogen infectivity of plasma (e.g., methylene blue and light, solvent/detergent, amotosalen and UVA, and riboflavin and UV) and platelets (PLTs; e.g., amotosalen and riboflavin), and there is another one being developed for PLTs (UVC and strong agitation).3 The US Food and Drug Administration is currently evaluating some of those methods.* All of them are aimed at the destruction of pathogen infectivity, at least to the level of detection with current assays, by damaging the nucleic acid of the pathogens. So in our opinion, those methods fall strictly into what can be defined as pathogen inactivation methods. However, not all the manufacturers are using that terminology, and some refer to their method as a pathogen reduction method. In our opinion, the differences in the terminology are provoking some misunderstandings and lack of standardization in the transfusion medicine community.

To avoid that, we propose to group those technologies aimed at damaging the infectious capacity of the pathogens into what can be referred to as “pathogen inactivation methods,” as has been the practice in the case of plasma derivatives and as was recently used in a review in TRANSFUSION.4 However, since none of the currently available methods can guarantee the complete sterility of the treated blood components, we suggest using the term “pathogen-reduced blood component” to refer to the treated unit itself. CONFLICT OF INTEREST ML has received research grants and lecture fees from Cerus Corp. and Terumo BCT. JC has received lecture fees from Cerus Corp. and Terumo BCT. JM has received research grant from Cerus and currently serves on advisory board of Fresenius Kabi. CP, HK, and JPA have disclosed no conflicts of interest.

Miguel Lozano, MD, PhD1 e-mail: [email protected] Joan Cid, MD, PhD1 Chris Prowse, MA, DPhil, FRCPathol2 Jeffrey McCullough, MD, PhD3 Harvey G. Klein, MD4 James P. Aubuchon, MD, PhD5 1 Department of Hemotherapy and Hemostasis University Clinic Hospital Barcelona, Spain 2 Faculty of Medicine University of Edinburgh Edinburgh, UK 3 Department of Laboratory Medicine and Pathology University of Minnesota Minneapolis, MN 4 Department of Transfusion Medicine Clinical Center National Institutes of Health Bethesda, MD 5 Puget Sound Blood Center Seattle, WA

REFERENCES 1. Horowitz B. Inactivation of viruses found with plasma proteins. Biotechnology 1991;19:417-30. 2. Burnouf T, Radosevich M. Reducing the risk of infection from plasma products: specific preventative strategies.

*Note added in proofs. US Food and Drug Administration approved amotosalen system for plasma and platelets in December 16 and 19, 2014, respectively. http://www.fda.gov/ NewsEvents/Newsroom/PressAnnouncements/ucm427111.htm http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ ucm427500.htm C 2015 AABB V

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Blood Rev 2000;14:94-110. 3. Lozano M, Cid J. Pathogen inactivation: coming of age. Curr Opin Hematol 2013;20:540-5. € ner A, Simon TL. Pathogen inactivation 4. Klamroth R, Gro and removal methods for plasma-derived clotting factor concentrates. Transfusion 2014;54:1406-17.