Stability of ADVATE, Antihemophilic Factor (Recombinant) Plasma/Albumin-Free Method, during simulated continuous infusion

Abstract

Continuous infusion of factor VIII (FVIII) concentrates during surgical procedures offers the potential for improved hemostatic control and reduced FVIII consumption, but requires stable FVIII concentrates. The stability of ADVATE, Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method (rAHF-PFM), was examined using various simulated conditions. Experiments performed with a multi-therapy 6060 pump showed FVIII recoveries of 95% or more after 48 h for multiple lots of high-potency and mid-potency rAHF-PFM, with or without heparin. Non-infused controls maintained at the same temperature showed similar FVIII recovery, demonstrating that the infusion system did not cause loss of FVIII activity. Supportive data generated using single lots of mid-potency or high-potency rAHF-PFM infused through a MEDEX or HARVARD syringe pump, or a CADD Pump-1, demonstrated FVIII recoveries of 83% or more at 24 or 48 h under all conditions tested. Additionally, rAHF-PFM was stable immediately after dilution in saline or saline/dextrose solutions, and after a 10-h exposure to ultraviolet and visible light. Taken together, these data demonstrate that rAHF-PFM is stable under conditions typically encountered during continuous infusion, and suggest that rAHF-PFM should be safe and effective when used for FVIII replacement by continuous infusion in patients with hemophilia A.

In vitro and in vivo stability of diluted recombinant factor VIII for continuous infusion use in haemophilia A

“…In the single‐pump system at a flow rate of 1 mL h −1 , loss of diluted KG‐FS (to ∼75%) was most marked in the first 2 h compared with undiluted KG‐FS, after which time a gradual increase of levels occurred to ∼100% at 24 h. In the double‐pump, Y‐infusion system, in which 0.9% saline was ‘infused’ at 10 mL h −1 along with the KG‐FS at 1 mL h −1 , there were greater losses because of the infusion of the 10‐fold larger volume of saline concomitantly with the rFVIII concentrate. With undiluted KG‐FS, the initial loss to ∼75% recovered to 84% by 12 h, and with diluted KG‐FS, the recovery at 1 h was only 35%, increasing gradually to 80% by 24 h. The initial loss of rFVIII under flow systems, observed by others as well [19], is likely because of the adsorption of the protein to the surface of the tubing.…”

Continuous infusion of simoctocog alfa in haemophilia A patients undergoing surgeries

“…Stability studies performed in the early 1990s showed that most concentrates were stable after reconstitution at room temperature for 3 days or more . The newer recombinant products have shown extended stability over 24‐48 hours . However, for safety reasons it is advisable to test the stability of each concentrate intended for use with the particular infusion set to be used.…”

FVIII administration in surgery

“…Although not an approved indication in the US or EU, stability studies under simulated conditions of continuous infusion have demonstrated that Advate was stable under all conditions tested [5]. In addition, we have recently investigated the stability of Advate under the conditions described by Takedani (personal communication) and have found Advate to be compatible.…”