The Food and Drug Administration (FDA) first approved PEGylated product in 1990, since then PEGylation, as a modification procedure for enhancing biomedical efficiency and physicochemical properties of therapeutic proteins has been extensively used. Recombinant proteins are prone to rapid degradation due to proteolysis or may have a brief circulating half-life due to low renal filtration. These limitations can be overcome by PEGylation, where polyethylene glycol chains are linked to peptides and protein molecules. The quality by design (QbD) paradigm helps to develop a process design spaces which describes the interactions and multidimensional effects of method variables on critical quality attributes of therapeutic proteins. The complexities involved in manufacturing processes have led to the development of strategies to establish a design space, ensuring reliable and reproducible outcomes. QbD approach in process optimization allows simultaneous screening of process variables, thus reducing the number of tests conducted as compared to the traditional approach based on a trial and error method. An approach to QbD using the design of experiments (DOE), has been used to establish a design space for PEGylation of recombinant proteins. The aim of this paper is to provide a systematic approach for implementing quality by design for development of a protein PEGylation process.
Key words: Polyethylene glycol (PEG), quality by design (QbD), critical quality attributes (CQAs), critical process parameters (CPPs), design of experiments (DOE) and design space.
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