Development of a lyophilized formulation of interleukin-2.

Native human interleukin-2 (IL-2) comprises a group of glycoproteins of MW 13,000-17,500. Recombinant human IL-2 (rhIL-2) (Cetus) is derived from E. coli and is not glycosylated. We have evaluated several processes for manufacturing rhIL-2, based on different chaotropic agents for solubilization of insoluble protein pastes. Formulation work carried out with material purified by one of these processes is reported here. Our studies have indicated that the presence of a stabilizer in the form of an amorphous excipient, such as amino acids, a non-ionic surfactant (polysorbate 80), hydroxypropyl-beta-cyclodextrin or human serum albumin was essential for preservation of rhIL-2 during lyophilization. Each of these formulations exhibited its own unique problems. We have overcome these problems through a systematic formulation development program and have been successful in developing several lyophilized formulations of rhIL-2 with optimum properties and performance.