The increasing occurrence of metabolic diseases has prompted a growing demand for peptides. Olivier Ludemann-Hombourger, Global Director of Innovation & Technology at the PolyPeptide Group, discussed how to scale up existing technology to manufacture peptides in a sustainable and cost-effective manner.
PolyPeptide, a CDMO specialising in peptide manufacturing, has developed several initiatives to achieve this scale-up. The company relies on modular manufacturing lines, which use optimally sized reactors instead of single large-scale reactors. This approach enhances flexibility, reduces risk, and shortens implementation time.
To enhance sustainability, Ludemann-Hombourger proposed a green agenda centred on the four concepts of reduce, recycle, replace, and avoid. On average, PolyPeptide successfully recycles over 90% of acetonitrile waste at its Belgium site and is developing DMF recycling methods, tackling challenges like impurities and nitrosamine content. These efforts saved over 500 cubic meters of DMF in 2023 and reduced relative solvent usage by 23.5% compared to the previous year.
The majority of the solvent is consumed during the SPPS (Solid Phase Peptide Synthesis) process in the washing steps between the coupling and protection steps. Solvent usage during SPPS was cut by 50% using a percolation washing method developed through computational modelling, pilot testing, and industrial implementation.
Furthermore, PolyPeptide is exploring greener solvent alternatives such as DMSO and NBP-ethyl acetate mixtures. Ludemaan-Hombourger emphasised that PolyPeptide are active in this sustainable space, he said: “Several publications have been made in the past by PolyPeptide. In order to support this this research programme, the goal is to search for solvent alternative, which is as good as DMF and remains cost efficient as well.”
Ludemann- Hombourger also examined how resin branching techniques maximise peptide output without increasing reactor volume. Introducing branching techniques led to promising results; this strategy led to higher peptide yields while maintaining or decreasing the resin’s final volume. Ludemann-Hombourger described the implications of these results: “It (resin branching) has great potential to debottleneck the throughput of the SPPS reactor, not only by increasing the volume or multiplying the reactor but getting more peptide out of a certain reactor capacity.”
Modular reactor designs play an important role in shaping sustainable practices, and innovative SPPS techniques to meet large-scale peptide demand. In 2023, 12.5% of PolyPeptide’s development programs incorporated green solvents, illustrating progress toward greener, more efficient peptide manufacturing.
