IntroductionPegaspargase, a pegylated asparaginase, is a core component in the treatment of acute lymphoblastic leukemia. Pegaspargase in liquid form has a limited shelf life of 8 months due to depegylation, leading to changes in purity and potency over time. Lyophilization is an approach that can improve the stability of biological drug conjugates.MethodsHere we describe the development of a lyophilized formulation of pegaspargase and present results of a series of tests demonstrating that the lyophilized form has comparable physicochemical properties to the liquid form.ResultsStability tests of critical quality attributes, including purity, potency, aggregates and total free polyethylene glycol, demonstrate that lyophilized pegaspargase remains stable for at least 3 years, with optimum stability achieved with storage under refrigerated conditions (2–8 °C).ConclusionsLyophilization improved the stability of pegaspargase without altering other physicochemical properties, permitting a prolonged shelf life of at least 2 years when stored at 2–8 °C. This may enable greater storage flexibility and allow for better management of pegaspargase.FundingStudy Sponsor: Baxalta (now part of Takeda). Publication Sponsor: Servier Affaires Médicales.Electronic supplementary materialThe online version of this article (10.1007/s12325-019-00988-5) contains supplementary material, which is available to authorized users.