Stability of lyophilized and reconstituted plasma/albumin-free recombinant human factor VIII (ADVATE rAHF-PFM)

Haemophilia. 2005 Sep;11(5):492-6. doi: 10.1111/j.1365-2516.2005.01128.x.

Abstract

Traditionally the serum protein albumin has been used to stabilize lyophilized recombinant factor VIII (rFVIII) products. Advanced rFVIII products have now been developed that employ other stabilizers. ADVATE antihaemophilic factor (recombinant), plasma/albumin-free method (rAHF-PFM) utilizes trehalose and mannitol as stabilizers in the lyophilized preparation. An extensive in vitro evaluation was conducted on the stability of rAHF-PFM as measured by retained activity over time. Both lyophilized and reconstituted rAHF-PFM were analysed, and the full range of available potencies were tested under varying temperature conditions. Lyophilized rAHF-PFM exhibited a high degree of stability under a range of conditions. The mean retained activity of 15 rAHF-PFM lots (ranging from low to maximal potency) at 5 degrees C for 30 months was 91.6% (95% CI, 88.9-94.3%) of initial potency. rAHF-PFM also remained highly stable after storage at room temperature for 18 months, with 82.0% (95% CI, 79.2-84.9%) of initial activity retained at 25 degrees C and 79.1% (95% CI, 76.2-81.9%) at 30 degrees C. All other parameters, including moisture, appearance, solubility, pH and aggregation remained within the established product specifications. The mean retained activity after 1 month of storage at 40 degrees C was 94.0% (95% CI, 92.4-95.6%). A high temperature excursion to 40 degrees C for 2 weeks did not compromise subsequent stability of the lyophilized powder either under refrigeration or at room temperature. Reconstituted samples from 11 rAHF-PFM lots retained an average of 92.0% (95% CI, 89.8-94.3%) activity after 24 h. The present study provides evidence of good stability at differing temperatures of an albumin-free formulated rFVIII product.

MeSH terms

  • Chemistry, Pharmaceutical
  • Drug Stability
  • Factor VIII / chemistry*
  • Freeze Drying
  • Humans
  • Preservatives, Pharmaceutical
  • Recombinant Proteins / chemistry
  • Serum Albumin
  • Temperature

Substances

  • Preservatives, Pharmaceutical
  • Recombinant Proteins
  • Serum Albumin
  • F8 protein, human
  • Factor VIII