Can the pharmaceutical substance Tirzepatide be efficiently manufactured using green solvents?

Purpose and goal:

PolyPeptide (PPL) in Limhamn, Malmö, and Red Glead Discovery (RGD) in Lund will explore the feasibility for developing a significantly more sustainable manufacturing of peptides. The global demand for the drugs Mounjaro and Zepbound, which is used to treat diabetes and obesity, is huge. A limiting factor in the supply is efficient manufacturing of the peptide-based active ingredient, tirzepatide.

PPL and RGD will therefore together evaluate the scope of developing an effective manufacturing process for tirzepatide, without using the toxic solvent N,N-dimethylformamide (DMF). Expected results and effects:

This project applied on a relatively large and complex peptide can significantly push the chemistry boundaries of green sustainable manufacturing processes of peptides forward. Furthermore, the project has the potential to accentuate Sweden at a global level as a natural arena for sustainable innovation, development and manufacturing of peptide-based molecules used for pharmaceuticals and other type of products.

Approach and implementation:

This feasibility project will be performed applying stepwise experimental work and in close collaboration and with knowledge transferring between RGD and PPL. It involves investigations at laboratory scale of the synthesis of tirzepatide using Solid-Phase Peptide Synthesis (SPPS) including optimization of suitable solvents for most efficient synthesis.

Then a scale-up of the developed laboratory protocol is to be performed, to get a DMF-free process that can be transferred for further development suitable for a commercial manufacturing process at PPL.