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The primary measures regarding pathogen safety are selection of healthy donors donating in centers with appropriate epidemiologic data for the main blood\u2010transmissible viruses, screening donations for the absence of relevant infectious blood\u2010borne viruses, and release of plasma pools for further processing only if they are nonreactive for serologic markers and nucleic acids for these viruses. Despite this testing, pathogen inactivation and\/or removal during the manufacturing process of plasma\u2010derived clotting factor concentrates is required to ensure prevention of transmission of infectious agents. Historically, hepatitis viruses and human immunodeficiency virus have posed the greatest threat to patients receiving plasma\u2010derived therapy for treatment of hemophilia or von Willebrand disease. Over the past 30 years, dedicated virus inactivation and removal steps have been integrated into factor concentrate production processes, essentially eliminating transmission of these viruses. Manufacturing steps used in the purification of factor concentrates have also proved to be successful in reducing potential prion infectivity. In this review, current techniques for inactivation and removal of pathogens from factor concentrates are discussed. Ideally, production processes should involve a combination of complementary steps for pathogen inactivation and\/or removal to ensure product safety. Finally, potential batch\u2010to\u2010batch contamination is avoided by stringent cleaning and sanitization methods as part of the manufacturing process.<\/jats:p>","DOI":"10.1111\/trf.12423","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T01:10:28Z","timestamp":1381540228000},"page":"1406-1417","source":"Crossref","is-referenced-by-count":44,"title":["Pathogen inactivation and removal methods for plasma\u2010derived clotting factor concentrates"],"prefix":"10.1111","volume":"54","author":[{"given":"Robert","family":"Klamroth","sequence":"first","affiliation":[{"name":"Center for Vascular Medicine Vivantes Klinikum im Friedrichshain  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albrecht","family":"Gr\u00f6ner","sequence":"additional","affiliation":[{"name":"Preclinical Research and Development, Pathogen Safety CSL Behring  Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toby L.","family":"Simon","sequence":"additional","affiliation":[{"name":"Plasma Research and Development\/CSL Plasma CSL Behring  King of Prussia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,9,30]]},"reference":[{"key":"e_1_2_15_2_1","unstructured":"Kcentra\u2122 (Prothombin Complex Concentrate [Human]). 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