Pathogen inactivation of RBCs: PEN110 reproductive toxicology studies.

Background: The novel PEN110 chemistry (INACTINE, V.I. Technologies) process for the purification of blood for transfusions involves treating WBC-reduced RBCs with PEN110 to inactivate a wide spectrum of pathogens. The washed RBC preparation has a residual PEN110 level of less than 0.00005 mg per mL. It is important to verify that the trace amounts of residual PEN110 in blood prepared for transfusions will not produce adverse effects on reproduction, fertility, or fetal development.

Study Design And Methods: A fertility and early embryonic development study was conducted in male and female Sprague-Dawley rats at IV doses of up to 0.5 mg PEN110 per kg of body weight following standard regulatory protocols. A fetal developmental study was conducted in Hra:(NZW)SPF pregnant rabbits at IV doses of up to 1.0 mg per kg of body weight following standard regulatory protocols. In both cases the highest dose was shown to be a maximum tolerated dose in pregnant animals based on body weight gain during pregnancy.

Results: In the fertility and early embryonic development study, no treatment-related effects were noted on estrous cycles, pregnancy rate, implantation sites, corpora lutea, number of resorptions, and live embryos in female rats or sperm motility, sperm morphology, and sperm counts in male rats. In the fetal developmental study, PEN110 had no effect on embryofetal viability and growth. This is consistent with other data indicating that PEN110 is rapidly cleared by urinary excretion. On a mg per kg of body weight dose basis, the no-observed-effect level doses for rats in the fertility study and rabbits in the developmental study were 2,000 and 4,000 (320 and 1,300 scaled to dose per unit body surface area [DBSA]) times that which a person would receive given 1 unit of treated blood. Considering the cumulative animal dosages, the safety factor values increase to 48,000- and 60,000-fold (7,700 and 19,400 scaled to dose per unit body surface area).

Conclusion: These results indicate that the trace amount of residual PEN110 in the purified blood component is well below the level that could present a risk of reproductive toxicity to the patient.