Funded by CSL Behring.
Pathogen inactivation and removal methods for plasma-derived clotting factor concentrates
Article first published online: 30 SEP 2013
© 2013 American Association of Blood Banks
Volume 54, Issue 5, pages 1406–1417, May 2014
How to Cite
Klamroth, R., Gröner, A. and Simon, T. L. (2014), Pathogen inactivation and removal methods for plasma-derived clotting factor concentrates. Transfusion, 54: 1406–1417. doi: 10.1111/trf.12423
- Issue published online: 12 MAY 2014
- Article first published online: 30 SEP 2013
- Manuscript Accepted: 1 AUG 2013
- Manuscript Revised: 26 JUL 2013
- Manuscript Received: 6 JUN 2013
- CSL Behring
Pathogen safety is crucial for plasma-derived clotting factor concentrates used in the treatment of bleeding disorders. Plasma, the starting material for these products, is collected by plasmapheresis (source plasma) or derived from whole blood donations (recovered plasma). The primary measures regarding pathogen safety are selection of healthy donors donating in centers with appropriate epidemiologic data for the main blood-transmissible viruses, screening donations for the absence of relevant infectious blood-borne 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-derived 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-derived 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-to-batch contamination is avoided by stringent cleaning and sanitization methods as part of the manufacturing process.