Advancing A Novel Vascular Calcification Inhibitor API From Lab-Scale To Tox-Batch Manufacturing Successfully

A leading pharma company had developed a small molecule drug candidate to treat vascular calcification disorders using an 8-step synthetic process. The company decided to partner with Syngene for the chemical development of the molecule for non-GMP and GMP manufacturing.

The Syngene team recommended a thorough mechanistic investigation to satisfy Safety, Environment, Legal, Economics, Control, and Throughput (SELECT) criteria before preparing the first few kilograms of this molecule in bulk. We developed an improved and scalable method based on six factors to ensure a first-time-right manufacturing process. These included chemical yield, cycle time, number of chemical steps, isolation of all intermediates in reasonably pure form, use of higher molecular weight protecting group and reagents, and several energy-consuming operations.

Syngene went on to successfully demonstrate the effectiveness of the new process by manufacturing 10 kg technical batches of the molecule. We are now proceeding with 50kg GMP manufacturing of this novel chemical entity for its use in first-in-human clinical trials.