Excluding donors with high anti-A and anti-B titers has minimal impact on the finished IVIG product titers due to ABO antibody neutralization and the dilution factor in the manufacturing pool.

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.

No abstract

Human intravenous immunoglobulin (IGIV) has been in use for the past 20 years. This biological product is commonly provided in liquid or lyophilized dosage form. When the lyophilized product is rehydrated, it is usually administered within 2-3 h from time of complete dissolution. While this practice is advisable whenever possible, occasionally the patient or care-giver may need to delay the infusion. Hence, a study of the stability of lyophilized IGIV after reconstitution with water for injection was conducted. The reconstituted product was stored either in its original glass container or pooled into poly(vinyl chloride) (PVC) bags. The effect of extended storage on the active ingredient (IgG), excipients (glucose, albumin) and extractables [sodium from glass vials, and di-(2-ethyl-hexyl) phthalate and cyclohexanone from PVC bags] was evaluated. The stability of the active ingredient was evaluated by physico-chemical tests (molecularsize distribution, pH, appearance, total protein), monitoring titres of a specific antibody (hepatitis B surface antigen) and an antibody functional test (bacterial opsonization). To evaluate the risk of microbial contamination during reconstitution and pooling procedures, sterility, pyrogen and animal-safety tests were included in the protocol. The potential of IgG polymerizing in solution during storage and subsequent complement activation was evaluated by assaying for non-specific binding of complement (anti-complement activity). Results show that aseptically reconstituted IGIV is stable and remains sterile up to 48 h at 5 degrees C. The reconstituted product was also found to be stable at room temperature (25 degrees C) up to 12 h.