In vitro stability of two formulations of recombinant activated factor viia reconstituted in inappropriate solvents or at inappropriate volumes

Current difficulties and recent advances in bypass therapy for the management of hemophilia with inhibitors: a new and practical formulation of recombinant factor VIIa

“…Another study demonstrated that rFVIIa-RT remained physically and chemically stable at 25°C (77°F) for 6 hours after reconstitution with sterile water for injection, physiologic saline, or histidine diluent (Table 1). 46 In this study, rFVIIa-RT was also shown to be stable at 5°C (41°F) for up to 24 hours when reconstituted with inappropriate diluents (sterile water for injection or physiologic saline) or the recommended histidine diluent. This is of interest to note in urgent or critical situations where only sterile saline or water for injection may be available for reconstitution.…”

“…This is of interest to note in urgent or critical situations where only sterile saline or water for injection may be available for reconstitution. rFVIIa-RT stability is also maintained with various “incorrect” volumes of diluent 46. Reconstitution in double or half of the histidine solvent does not adversely affect stability; however, there is still a potential for dosing errors because the target final dose cannot be achieved if the correct diluent volume is not used 46…”

“…Histidine, a naturally occurring amino acid, is used as a buffering agent in other marketed factor replacement products and thus has a history of safe use in this patient population 45,46…”

“…This article was published in Clinical Therapeutics, Petersson et al46 Copyright © 2008, Elsevier. Abbreviation: rFVIIa-RT, room temperature stable activated recombinant factor VII.…”

Optimizing on‐demand treatment with NovoSeven® room temperature stable

“…Samples were also shown to be stable after 5 days of daily alternation between storage at 5°C (refrigerated) and 30°C (high room temperature) [14]. Finally, the reconstituted product retained activity for 6 h and 24 h when stored at 25°C and 5°C, respectively [14] – a finding confirmed by another in vitro study in which the product remained chemically and physically stable for ≤6 h of storage at 25°C and for ≤24 h at 5°C, even if an inappropriate type or volume of solvent was used [15].…”