Dr. Sharadsrikar Venkatesan Kotturi, chief scientific officer of Neuland Labs overviews the challenges and opportunities of sustainable industrial manufacture of peptide APIs

Nonetheless, the environmental and economic sustainability of industrial peptide manufacturing remains a critical bottleneck. Traditional solid-phase peptide synthesis( SPPS) methods are energy- and solvent-intensive, yielding high E-factors( 100 – 10,000 kg waste / kg API) and carbon intensities that exceed those of most small molecule APIs.

This paper evaluates the scientific and industrial transition toward sustainable peptide API production, integrating innovations across three converging domains: process optimisation in chemical synthesis, green chemistry and solvent minimisation, and biotechnological routes, including chemo-enzymatic and microbial methods. Drawing from recent advances by industry leaders and academia, it outlines how sustainability is being embedded into the entire lifecycle of peptide APIs, from raw material sourcing to downstream purification.

Market & industrial context

Peptide APIs now serve diverse therapeutic areas, including endocrinology( GLP-1 analogues, insulin derivatives), oncology, cardiovascular diseases and

No. Industrial Case / Source Key Sustainability Outcome

1 Isidro-Llobet et al., 2019, J. Org. Chem.

Multi-company initiative( GSK, Novartis et al.): identified peptide APIs as top green-chemistry priority; initiated benchmarking of solvent & reagent intensity

5 Sadatshojaei et al., 2021, Elsevier Book Ch.

infectious diseases. Demand has accelerated following the commercial success of long-acting GLP-1 receptor agonists( e. g. semaglutide and liraglutide) and the advent of peptide-drug conjugates.

However, the current manufacturing paradigm relies largely on legacy SPPS processes using large quantities of hazardous reagents, such as piperidine and N, N- dimethylformamide( DMF). 1 These not only drive high material intensity but also pose occupational and environmental hazards.

Industry consortia like the ACS Green Chemistry Institute’ s Pharmaceutical Roundtable( GCI PR) identified green peptide API manufacture as a top unmet sustainability need. In response, pharmaceutical companies

Enzyme-based antibiotic peptide synthesis; low-toxicity solvents; emerging use of supercritical CO₂ for purification

Table 1 – Comparative sustainability metrics in industrial case studies of peptide manufacture

have initiated the collaborative benchmarking of solvent usage, atom economy and E-factors, catalysing a systemic shift toward circular chemistry principles and biocatalytic integration.

Chemical synthesis process optimisation

SPPS remains the industrial standard for manufacturing short- to mediumlength peptides. First introduced in the 1960, this methodology enables automation and scalability but suffers from inefficiencies at large scale due to repetitive coupling, washing, and deprotection cycles.

Recent optimisations focus on reagent stoichiometry control, real-time reaction monitoring, and resin engineering. Novo Nordisk researchers have highlighted

24 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981