Lopez, John, Gallou, Fabrice, Kekessie, Ivy, Wegner, Katarzyna, Martinez, Isamir, Kopach, Michael E., White, Timothy D, Tom, Janine, Koenig, Stefan, Payne, Philippa, Eissler, Stefan, Mukherjee, Subha, Isidro-Llobet, Albert, Ludemann, Olivier, Richardson, Paul, Sejer Pedersen, Daniel and Vandenbos, Leendert (2024) Process Mass Intensity (PMI): A holistic analysis in current peptide manufacturing processes, informing sustainability in peptide synthesis. The Journal of Organic Chemistry, 89 (7). pp. 4261-4282. ISSN 0022-32631520-6904

Abstract

Small molecule therapeutics represent the majority of FDA-approved drugs. Yet, many attractive targets are poorly tractable by small molecules, generating a need for new therapeutic modalities. Due to their biocompatibility profile and structural versatility, peptide-based therapeutics are potentially a possible solution. Additionally, in the past two decades, advances in peptide design, delivery, formulation and devices have occurred making therapeutic peptides an attractive modality. However, peptide manufacturing is often limited to Solid Phase Peptide Synthesis (SPPS), liquid phase peptide synthesis (LPPS) and to a lesser extent hybrid SPPS/LPPS, with SPPS emerging as a common platform technology for peptide synthesis. SPPS involves the use of excess solvents and reagents which have negative impact on the environment, thus highlighting the need for newer technologies for reduction of environmental footprint.
Herein, twelve American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable (ACS GCIPR) member companies with peptide-based therapeutics in their portfolio, have compiled Process Mass Intensity (PMI) metrics to help inform the sustainability efforts in peptide synthesis. This includes PMI assessment on 40 synthetic peptide processes at various development stages in pharma, classified according to development phase. This is the most comprehensive synthetic peptide assessment of environmental metrics. The synthetic peptide manufacturing process was divided into stages (synthesis, purification, isolation) to determine their respective PMI. On average, the synthetic peptide SPPS (PMI ~ 13,000) does not compare favourably with other modalities such as small molecules (PMI median 168−308) and biopharmaceuticals (PMI ∼8300). Revealing that the high PMI for peptide synthesis warrants more environmentally friendly processes in peptide manufacturing.

Item Type:	Article
Date Deposited:	04 Aug 2024 00:46
Last Modified:	04 Aug 2024 00:46
URI:	https://oak.novartis.com/id/eprint/49304