TIDEs (therapeutic peptides, oligonucleotides, and related molecules) represent a rapidly expanding market that has gained significant momentum due to the recent success of Glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of obesity, diabetes and as cardiovascular and kidney diseases. Chemical synthesis remains the dominant manufacturing route for candidates containing approximately 10–40 amino acids and includes non-proteinogenic amino acids. Consequently, various combinations of solid-phase peptide synthesis (SPPS), liquid-phase peptide synthesis (LPPS), hybrid approaches, or tag-assisted peptide synthesis (TAPS) can be applied to achieve full-sequence assembly. However, identifying the most eco-efficient pathway through experimental trials alone is impractical because of the vast number of possible process combinations and the growing variety of green solvent alternatives. Therefore, process simulation studies—widely established in chemical engineering—must be adapted to the specific physicochemical characteristics of these large, multi-component molecules. This paper provides an overview of the current state of research and illustrates potential process improvements enabled by digital twin technologies as exemplified for the first manufacturing steps of tirzepatide.
Uhl et al. (Tue,) studied this question.