Development of a Lyophilized Formulation of Pegaspargase and Comparability Versus Liquid Pegaspargase.

INTRODUCTION

Pegaspargase, 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.

METHODS

Here 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.

RESULTS

Stability 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).

CONCLUSIONS

Lyophilization 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.

FUNDING: Study Sponsor: Baxalta (now part of Takeda). Publication Sponsor: Servier Affaires Médicales.