In January 2023, when news arrived that patient enrollment for the Phase I clinical trial of Suraxavir Marboxil Tablets had been completed ahead of schedule, Director He, the head of synthesis at the Hangzhou Drug R&D Center, felt both excitement and pressure. At that moment, it was as if he had crouched at the track, only to have the baton suddenly passed into his hands—filling him with both excitement and nervousness.
He stared at the calendar on his desk, circling key dates repeatedly with a pen."One, two, three... Only 145 days left until the deadline for completing the process validation of the active pharmaceutical ingredient (API)!"
Time hung like a gleaming sword overhead, yet the challenge of altering the synthesis route for the starting material still loomed large before the synthesis team.
One early morning in the lab, an anomaly occurred during a crystallization step—suspected isomer precipitation threatened to compromise product quality. "Upon receiving the alert, I rushed to the scene immediately. By monitoring and analyzing real-time in-process control data, we halted the reaction in time. We worked until daybreak and ultimately resolved the issue through slurry refining," Director He recalled this vividly.
The path of R&D is fraught with challenges. The change in the starting material completely overturned the established production process. Under the GMP framework, zero errors were mandatory to keep the project on track—a monumental challenge.
Skilled and decisive, drawing on rich experience accumulated from dozens of API industrialization process developments, the project team made a bold call: skip the process confirmation batches and move directly from lab-scale-up to formal process validation.
Faced with multiple challenges including an extended process route, an extremely tight schedule and high difficulty in process control, the synthesis team never flinched. Through repeated discussions, they immediately established a comprehensive in‑process control system, covering four HPLC reaction monitors and five intermediate drying checks, enabling precise monitoring and regulation of every production step and ensuring process stability and reproducibility.
“We can afford to take bigger steps, but every step must be taken with full focus and solid execution,” Director He remarked.
To save time and mitigate risks, the project team boldly adopted a batching production mode. Director He recalled that from April to June 2023, six to seven researchers from the Hangzhou synthesis team stayed on-site in Ganzhou until the completion of process validation.
When the final batch of API passed inspection and the QC report clearly stated “all indicators meet predetermined specifications”, they exchanged relieved smiles. That smile was one of weary relief—a medal of victory earned through countless days and nights of hard work.
Process optimization and research sample preparation run through the entire drug development lifecycle: from Phase I clinical trials, chronic toxicity studies, reproductive toxicity tests, and Phase II clinical trials, through extended process route research, Phase III clinical trials and process validation batches, to new formulation development and eventual product launch. Ongoing efforts to reduce costs and improve efficiency through process refinement will continue.