Inactivation efficacy of INTERCEPT for a broad spectrum of viruses and parasites

Despite the diligent implementation of strategies to minimize the risk of transfusion-transmitted infections, blood recipients, who are often vulnerable due to massive bleeding or immunosuppressive treatments are still at risk.

Current mitigation strategies have limitations, and the constant emergence of new pathogens result in a persistent threat to blood safety and availability. This could be mitigated by the use of robust pathogen inactivation¹.

Pathogen inactivation, a proactive approach, addresses a broad spectrum of pathogens, reduce the need for new testing, and maintain blood continuity and availability for sustained pandemic preparedness².

Log reduction factors of ≥4.0 log are generally considered the minimum requirement for viruses and parasites based on regulatory standards per the Committee for Human Medicinal Products³. Moreover, clinically relevant levels of infectivity are difficult to define, and the wide variation in immune responses in healthy people and patients may be highly variable depending on disease, therapy, and underlying conditions. Thus, it seems best to assume that there is no safe level of contamination.

Pathogen inactivation systems with high log reduction enable blood product continuity and sustainability during emerging infectious diseases outbreaks, when no licensed screening tests are available⁴.

Inactivation studies are designed to investigate a system's ability to inactivate the highest infectivity levels to ensure maximum safety margins^5,6,7.

“Inactivation of a broad spectrum of viruses and parasites by photochemical treatment of plasma and platelets using amotosalen and ultraviolet A light”⁸ is a review article recently published in Transfusion. This review is a compendium of previously published or unpublished data that have been obtained to date and together demonstrate the performance of the INTERCEPT^TM Blood System ("INTERCEPT") to inactivate viruses and parasites.

Twenty-five enveloped viruses, six non-enveloped viruses and four parasites species were evaluated⁸:

• Twenty-five enveloped viruses, two non-enveloped viruses and four parasites species were sensitive to amotosalen and ultraviolet A light⁸.
• Log reduction factors of ≥4.0 log were reported for⁸:
  • 28 pathogens in platelet components in platelet additive solution
  • 19 pathogens in plasma
  • 14 pathogens in platelet components in 100% plasma

This review confirms INTERCEPT's ability to reduce transfusion-transmitted infectious risk from a broad range of viruses and parasites which may contaminate plasma and platelet components.

While this review is focused on the inactivation of viruses and parasites, INTERCEPT has proven efficacy to prevent transfusion-associated graft-versus-host disease and bacterial TTIs⁹, the most significant infectious risk in transfusion today^10,11.

References:
¹Marks PW, Epstein JS, Borio LL. Maintaining a safe blood supply in an era of emerging pathogens. J Infect Dis 2016;213: 1676-7.
²Domanovic D, Ushiro-Lumb I, Compernolle V, et al. Pathogen reduction of blood components during outbreaks of infectious diseases in the European Union: an expert opinion from the European Centre for Disease Prevention and Control consultation meeting. Blood Transfus 2019;17:433-48.
³European Medicine Agency, Committee for Proprietary Medicinal Products, Document CPMP/BWP/268/95, 1996.
⁴Rasongles P, Angelini-Tibert MF, Simon P, et al. Transfusion of platelet components prepared with photochemical pathogen inactivation treatment during a Chikungunya virus epidemic in Ile de La Reunion. Transfusion 2009;49:1083-91.
⁵Goodrich RP, Custer B, Keil S, et al. Defining "adequate" pathogen reduction performance for transfused blood components. Transfusion 2010;50:1827-37.
⁶McCullough J, Alter HJ, Ness PM. Interpretation of pathogen load in relationship to infectivity and pathogen reduction efficacy. Transfusion 2019;59:1132-46.
⁷Klasse PJ. Molecular determinants of the ratio of inert to infectious virus particles. Prog Mol Biol Transl Sci 2015;129:285-326.
⁸Lanteri M, Santa-Maria F, Laughhunn A, et all. Inactivation of a broad spectrum of viruses and parasites by photochemical treatment of plasma and platelets using amotosalen and ultraviolet A light. Transfusion 2020;00;1–13
⁹Benjamin RJ, Braschler T, Weingand T, et al. Hemovigilance monitoring of platelet septic reactions with effective bacterial protection systems. Transfusion 2017;57:2946-57.
¹⁰Castro G, Merkel PA, Giclas HE, et al. Amotosalen/UVA treatment inactivates T cells more effectively than the recommended gamma dose for prevention of transfusion-associated graft-versus-host disease. Transfusion 2018;58:1506-15.
¹¹Kleinman S, Stassinopoulos A. Transfusion-associated graft versus-host disease reexamined: potential for improved prevention using a universally applied intervention. Transfusion 2018;58:2545-63.