Evaluation of processing characteristics of photochemically treated pooled platelets: target requirements for the INTERCEPT Blood System comply with routine use after process optimization

Abstract

To ensure good performance of pathogen inactivation with the INTERCEPT blood system, specific target requirements must be met for platelet dose, volume, plasma content and residual red blood cells (RBCs) prior to photochemical treatment (PCT). A two-arm in vitro study was conducted to compare quality parameters of pooled platelet concentrates (PCs), either treated (test units) or nontreated (control units). PCs meeting European requirements were evaluated with reference to their compliance with INTERCEPT guard bands. Of 50 PCs (25 tests and 25 controls) meeting European quality requirements, 24% (three test and three controls units) did not reach INTERCEPT requirements, particularly in terms of sufficient volumes and RBC contamination. The buffy-coat optimization procedure assessed prior to this study ensured plasma contents well within target limits of 30 to 45%. Due to PCT-related in-process loss of 11% in volume (34.38 +/- 3.94) and in platelet dose (0.41 +/- 0.14), the mean platelet dose was significantly (P < 0.001) lower in test units: 3.1 +/- 0.3 versus 3.6 +/- 0.4 x 10(11). After treatment, six of the overall 25 test units (25%) would not have met the European guideline for platelet dose (3.0 x 10(11)). Before implementation of techniques for pathogen reduction, each centre should optimize processing steps during a validation procedure to ensure PC complying with INTERCEPT targets before and European targets after treatment. Besides buffy-coat optimization for sufficient plasma reduction, centrifugation profiles need to be optimized as well to prevent PC with low volumes and, in particular, with higher than acceptable RBC contamination.

Bacterial risk reduction by improved donor arm disinfection, diversion and bacterial screening

“…The Intercept system requires product standardization and the use of PAS. An 11% loss of platelets has been reported with the process (Picker et al , 2004). Removal of residual psoralen is required.…”

In vitro quality of single‐donor platelets treated with riboflavin and ultraviolet light and stored in platelet storage medium for up to 8 days

“…Exposure to ultraviolet (UV) radiation in the presence of the synthetic psoralen amotosalen (Intercept System, Cerus Corp., Concord, CA) was the first such technology to be licensed in Europe. Intercept treatment causes increased PLT activation and metabolism in vitro 1,2 and a reduction in the recovery and survival of PLTs after reinfusion to healthy subjects 3 . In two large multicenter clinical studies in stable patients, there was a reduction in PLT count increments after transfusion of amotosalen‐treated PLTs, mainly attributable to their lower dose 4,5 .…”

A flow cytometric method for detection and enumeration of low‐level, residual red blood cells in platelets and mononuclear cell products

“…The manufacturers and users of these devices are interested in having a measurement method sensitive enough to allow determination of device performance and process capability even if the level of cross‐cellular contamination is well below the regulatory recommendations. For example, Picker’s groups reported there are tight limits on the allowable rRBCs in blood products before pathogen inactivation owing to the unique nature of chemical and light treatments 12 . Their study demonstrated a need to modify existing blood product manufacturing processes to meet these tighter requirements that were outside of the range for standard hematology analyzers.…”

“…For example, Picker's groups reported there are tight limits on the allowable rRBCs in blood products before pathogen inactivation owing to the unique nature of chemical and light treatments. 12 Their study demonstrated a need to modify existing blood product manufacturing processes to meet these tighter requirements that were outside of the range for standard hematology analyzers. To measure the rRBCs, Picker used a flow cytometry (FC) method.…”