PEG–protein conjugates; regulatory requirements for characterization

PEGylated protein conjugates submitted as therapeutic products qualify for Biologics License Applications as new chemical entities or new molecular entities. Even an improved version of an existing product must still undergo regulatory consideration as a new product. This chapter reviews historical and current regulatory guidelines specific to PEGylated proteins illustrated by examples from currently marketed products. As analytical techniques improve, regulatory authorities expect characterization methodologies of biological products undergoing regulatory review to embody current state-of-the-art capabilities. Biosimilars of existing polyethylene glycol (PEG)–protein conjugates are also subject to regulatory scrutiny, particularly with reference to the development of antidrug antibodies. This chapter highlights various regulatory considerations required for characterization, but each product will have its own unique challenges based on the combination of the specific protein and the specific PEGylation strategy.