Development of a Lyophilization Formulation that Preserves the Biological Activity of the Platelet-inducing Cytokine Interleukin-11 at Low Concentrations

Recombinant human interleukin‐11 (rhIL‐11) is a licensed biological therapeutic product in at least one country and is used to combat thrombocytopenia during chemotherapeutic regimens, as well as undergoing clinical trials for a range of other disorders. Following attempts to lyophilize IL‐11 at low concentrations, it was clear that a significant loss of recoverable biological activity occurred. Investigation of a variety of factors, including the type of container in which the rhIL‐11 was lyophilized, revealed that surface adsorption to glass was a major factor resulting in loss of activity of rhIL‐11 in solution (> 40% reduction after 3 h at room temperature), in addition to losses of activity post‐lyophilization. To overcome this problem, different formulations containing combinations of human serum albumin (HSA), trehalose and Tween‐20 have been investigated. Two formulations were successful in entirely preserving the biological activity of rhIL‐11 through lyophilization and subsequent reconstitution (potency estimates of formulated relative to original material being ≥0.97). Accelerated degradation studies, performed at intervals over a six‐month period, demonstrated the stability of freeze‐dried rhIL‐11 using these formulations (predicted annual reduction in potency after storage at −20°C ≤1.4%). In conclusion, we have developed a working combination of excipients (0.5% HSA, 0.1% trehalose and 0.02% Tween‐20 in potassium phosphate buffer (pH 7.4)) to formulate a stable rhIL‐11 freeze‐dried product in glass containers, with no loss in potency. These findings should facilitate development of low dose rhIL‐11 products and be an indicator of caution to those using this and other material with similar physical properties, without taking appropriate precautions to avoid losses through adsorption.