PB1327 - Bioequivalence of a Generic Version of rFVIIa (Aryoseven) as Compared to the Branded Version of rFVIIa (Novoseven).

Background: Recombinant activated factor VIIa (rFVIIa) (Novoseven) was first approved by European Medicine Agency for treatment of patients with auto and allo-antibodies against factor VIII and IX. A generic version of factor VIIa namely Aryoseven is available in south-east Asian countries and used as a prohemostatic agent.

Aims: This study is focused on the comparison of several batches of currently available Novoseven and multiple batches of Aryoseven in standardized laboratory methods to demonstrate the equalance.

Methods: Four batches of Novoseven were obtain from commercial vendors. Four batches of Aryoseven were made available by UGA (Munich, Germany). These agents were reconstituted in sterile saline to obtain a working concentration of 100 mcg/ml to test their coagulant activity. Normal plasma samples, factor VII deficient plasma samples, plasma samples from various patient groups including liver disease and those on oral anticoagulant drugs were used to measure the effect of FVIIa on their clotting profile. Thrombin generation studies were carried out using the fluorogenic substrate method. The levels of FVIIa in various batches of both generic and branded versions of FVIIa were measured utilizing ELISa methods. The procoagulant actions of both types of FVIIa were also studied using thrombin generation marker measurements including F1.2 and TAT in various plasma systems.

Results: The results of the various tests comparing the two versions of recombinant Factor VIIa are shown in table 1. The two FVIIa preparations also produced comparable effects in the plasma samples with elevated PT and aPTT. The FVII antigen levels was comparable in both preparations. Thrombin generation markers such as F1.2 and TAT were generated at equivalent level by both agents in normal and pathologic plasma samples.

Conclusion(s): These studies demonstrate that the two versions of FVIIa are comparable. Furthermore these results warrant additional validation in animal models and clinical trials.