Sylvia Van Dorpe, Mathieu Verbeken, Evelien Wynendaele and Bart De Spiegeleer
The quality of a peptide drug mainly depends on its impurity profile, with the emphasis on the related impurities. These impurities may be biomedically active, alter the desired efficacy or induce unwanted toxicity, an aspect which is termed the “functional quality” of the peptide drug. Therefore, regulatory authorities have set up guidances or have legally established specification limits to assure a consistent purity of these peptide drugs. For the active pharmaceutical ingredients (APIs), the pharmacopoeial monographs are legally binding. Additional information can be found in regional and international guidelines. For the finished pharmaceutical drug products (FDPs) containing peptide active ingredients, only general guidelines are available. The construction of a complete related-impurity profile is very challenging due to the wide availability of different protecting groups, coupling agents and additives that may be used during peptide synthesis. In addition, chemical degradation, occurring during synthesis, formulation or at storage, may occur as well, including not only so-called pure chemical degradation but interaction with excipients as well. This review provides an update of the regulatory and scientific rationales behind the related impurities in peptide drugs.
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