Speciality Chemicals Magazine MAR / APR 2026 | Seite 26

PEPTIDES & PROTEINS

Although product heterogeneity and downstream purification challenges persist, these bioprocesses use water as solvent, dramatically lowering E-factors. 3 Emerging cell-free peptide synthesis platforms combine enzymatic amino-acid activation with ribosomal or non-ribosomal assembly, potentially providing a sustainable alternative for complex or cyclic peptides.

Industrial biocatalysis benefits from enzyme immobilisation( on silica, polymer or magnetic supports) to improve turnover numbers and reusability. Directed evolution has enhanced enzyme thermostability, allowing reaction integration into hybrid SPPS – CEPS workflows. Novo Nordisk and GlyTech are advancing immobilised ligase systems for insulin analogues and GLP-1 derivatives, targeting complete biocatalytic pathways by 2030.

Tables 1 and 2 show some comparative sustainability metrics and metrics of green performance respectively for some of the aforementioned studies. Such metrics demonstrate tangible industrial progress toward UN Sustainable Development Goal 12( Responsible Consumption & Production) while maintaining economic viability.

Challenges & future perspectives

While CEPS and enzymatic routes have proven conceptually sustainable, enzyme cost and turnover stability remain limitations. Industrial processes require turnover numbers > 106 mol product / mol enzyme to compete with purely chemical methods. Continuous flow biocatalysis may bridge this gap.

Purification and isolation of peptide APIs account for up to 50 % of total manufacturing cost and environmental impact. Chromatography solvents like acetonitrile and methanol and highpressure energy demands challenge sustainability. Efforts toward aqueous two-phase extraction, membrane separations and supercritical CO 2 chromatography are promising alternatives. 5

Regulatory agencies still require full analytical equivalence between green-manufactured and conventional APIs. The implementation of new solvents or biocatalytic steps thus demands extensive validation under GMP. Collaborative industry consortia, such as the PEP-GCI Network, are developing pre-competitive data packages to ease regulatory adoption.

Finally, artificial intelligence and machine learning are being applied to optimise solvent selection, coupling efficiency and process energy profiles. Digital twins of SPPS reactors allow for predictive simulation of solvent flows and waste outputs, supporting closed-loop production strategies aligned with the circular economy.

Toward a green peptide economy

By 2030, the peptide API sector is projected to surpass $ 35 billion / year, with sustainability serving as both a regulatory and market imperative. The integration of green chemistry, biocatalysis and digitalisation will define competitiveness.

Future-ready manufacturers will operate modular solvent-recycling plants, capable of switching between SPPS, CEPS and enzymatic routes based on cost-to-sustainability tradeoffs. Cross-industry collaboration is expected to accelerate development of bio-based reagents, renewable

solvent systems, and carbon-neutral peptide plants.

Conclusion

The industrial manufacture of peptide APIs is undergoing a profound transformation driven by environmental accountability and technological innovation. Through chemical process optimisation, the adoption of green chemistry and biotechnological integration, companies are simultaneously reducing solvent use, carbon intensity and cost.

Case studies from solvent-free SPPS to chemo-enzymatic exenatide demonstrate that sustainable peptide manufacturing is both technically feasible and economically advantageous. The convergence of enzymology, green process engineering and digital analytics positions the sector at the forefront of the green pharmaceutical transition. Continued collaboration between academia, industry and regulatory bodies will be essential to achieving a fully sustainable peptide economy where therapeutic innovation aligns with planetary stewardship. ●

26 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981