The US Food and Drug Administration (FDA) has approved the INTERCEPT Blood System for plasma, the first pathogen inactivation system for the preparation of plasma to reduce the risk of transfusion-transmitted infections.

The system inactivates pathogens through a photochemical process involving controlled exposure to ultraviolet light and the chemical amotosalen. The plasma is then purified to remove the chemical and its byproducts.

The INTERCEPT Blood System for plasma can be used to reduce pathogens in plasma derived from whole blood and plasma obtained by apheresis.

The system has proven effective in reducing a broad spectrum of viruses, bacteria, spirochetes, and parasites. However, there is no pathogen inactivation process that has been shown to eliminate all pathogens. Certain viruses (eg, human parvovirus B19) and spores formed by certain bacteria are known to be resistant to the INTERCEPT process.

“The approval of devices like the INTERCEPT Blood System allows blood establishments to prepare plasma that carries a lower risk of transmitting infectious pathogens through transfusion,” said Karen Midthun, MD, director of the FDA’s Center for Biologics Evaluation and Research.

The INTERCEPT Blood System for plasma, which is marketed by Cerus Corporation, has been approved in Europe since 2006 and was recently made available in the US under an Investigational Device Exemption study. The system is being used to prepare Ebola convalescent plasma for transfusion into acutely infected patients.

Clinical studies

Researchers investigated the safety and effectiveness of plasma prepared with the INTERCEPT Blood System in 6 clinical studies and 2 post-marketing studies.

The research showed no significant difference in coagulation factor activity between INTERCEPT-processed plasma and unprocessed fresh-frozen plasma (FFP) in healthy subjects.

There was no significant difference in prothrombin time or activated partial thromboplastin time between INTERCEPT-processed plasma and FFP in patients with coagulation factor deficiencies or in patients with liver disease.

In patients who underwent liver transplant, there was no significant difference in plasma use, hepatic artery thrombosis, or mortality whether patients received INTERCEPT-process plasma or FFP.

In a prospective, phase 3 trial and a retrospective study of patients with thrombotic thrombocytopenic purpura (TTP), there was no significant difference in the percentage of patients who achieved remission with INTERCEPT-treated plasma or FFP.

Adverse events

In a post-marketing study*, researchers analyzed acute transfusion reactions (ATRs) after 57,171 INTERCEPT-processed plasma components were transfused to 9669 patients. Thirty-two subjects (0.3%) experienced an ATR after 41 transfusion episodes (0.2%), including 5 subjects (0.05%) who experienced an ATR after more than 1 transfusion.

Six ATRs were considered serious and possibly or probably related to transfusion. There were 3 instances of allergic reaction or symptoms of allergic reaction (eg, rash, tachycardia, hypotension, respiratory symptoms, and chills), 2 cases of fluid overload, and 1 report of respiratory distress.

In another hemovigilance study, researchers compared the frequency of adverse events due to any of the 4 types of FFP prepared and delivered by the French Blood Establishment over a 10-year period—methylene blue, amotosalen, quarantine, and solvent-detergent.

The study showed that all types of FFP were associated with a low rate of adverse events. Per 10,000 deliveries, there were 7.14 events in the quarantine group, 4.86 in the solvent-detergent group, 4.16 in the amotosalen group, and 1.05 in the methylene blue group.

The package insert of the INTERCEPT Blood System for plasma warns that amotosalen-treated plasma has been associated with cardiac events.

In the aforementioned prospective trial of the system in patients with TTP, 5 patients treated with INTERCEPT-processed plasma and none with conventional plasma had adverse events in the cardiac system organ class.

This included angina pectoris (n=3), cardiac arrest (n=1), bradycardia (n=1), tachycardia (n=1), and sinus arrhythmia (n=1). None of the events resulted in documented myocardial infarction or death.

*Results have been updated since publication.

FDA approves pathogen inactivation system for plasma