Stabilization of selected therapeutic protein formulations

Abstract

Depending on the polyethylene glycol reagent and chemistry used to manufacture them, pegylated products may exhibit different degradation patterns under different storage conditions. To ensure product quality, it is essential to prevent degradation, which can occur when temperatures exceed optimal levels during manufacturing, storage, and shipping. To get a better understanding of degradation patterns, research has been conducted to evaluate the stability of pegylated products under various storage conditions. newlineResearch into degradation pathways of peginterferon alfa-2b and pegaspargase suggest that drug substance needs to be immediately and continuously converted to drug product during manufacturing campaign when the material is stored in liquid form. While peginterferon alfa-2b is observed to withstand repeated freezing and thawing process in absence of cryoprotectant, pegaspargase appears to loss structural integrity. This indicates peginterferon alfa-2b can be stored under frozen condition and therefore drug product manufacturing can be decoupled from drug substance manufacturing, which is not the case with pegaspargase. When stored in liquid form or upon exposure to high temperature conditions, both the products are observed to degrade mainly through depegylation. Results also indicate impact on structural integrity of pegaspargase upon exposure to high temperature. Such variety of degradation pattern indicates selection of polyethylene glycol reagent and pegylation chemistry are very crucial steps to the development of successful pegylated drug product and necessitates development of stable formulation, preferably lyophilized formulation. newlineProtein-polymer conjugate in peginterferon alfa-2b and pegaspargase is highly susceptible to have spontaneous hydrolysis which leads to removal of polyethylene glycol from protein moiety with time during storage. With such protein-polymer conjugates, lyophilization technology can be a saviour which can provide stable formulation over a desired period of time. Therefore, to newline