India Pharma Outlook Team | Monday, 29 September 2025
Syngene International has achieved a successful scale-up of the synthesis of a new active pharmaceutical ingredient for vascular calcification inhibition, progressing from lab-scale proof-of-concept to commercial-scale good manufacturing practice (GMP) production.
This accomplishment reinforces Syngene's ability to work with complex molecules and provide consistent, high-quality support for clinical development.
Initially, at the request of a global pharmaceutical partner, Syngene developed 50g of the target molecule at lab scale. Following improvements in the process, the company performed a 10kg manufacturing run at non-GMP scale, attaining 98 percent purity.
Also Read: Why Global Pharma Expects CDMOs to Be Ready for Joint Inspections
The work on the project has now progressed to GMP manufacture with 50kg manufactured for supply to clinical studies. A further 90kg GMP reload campaign is scheduled for Q2 2024, according to company updates.
This project and its successful development ensure that Syngene maintains its technical capability and capacity to support chemical development and manufacturing at commercial scale for clinical trials. The team has implemented a detailed mechanistic investigation to support scalable and safe manufacture, consistent with SELEC criteria (Safety, Environment, Law, Economics, Control, and Throughput).
Main challenges included the isolation of unstable intermediates, the management of the phosphorylation of the hydroxyl groups, and also the mild deprotection methods for purification purposes. A key step was the oxidation of the phosphorous using hydrogen peroxide, which presented safety factors, with a laboratory scale adiabatic temperature rise potential of 200°C. Syngene successfully optimized this step to allow for a safe first-time-right process with high-grade toxicology material delivered on time.
By demonstrating a capable and scalable 8-step synthesis, Syngene has established itself as a reliable partner in moving this life-saving small molecule into first-in-human clinical trials.
