The Challenge

Our client approached us with a project where they required API for toxicology and phase 1 clinical studies. The product had not been manufactured at scale previously; however, there was literature precedent for a three step process to prepare the compound. The proposed process had two main scale-up liabilities.

  1. The first synthetic intermediate was highly toxic, susceptible to polymerization, had a low boiling point (59-60℃) and was prepared using a hazardous oxidant, chromium trioxide.
  2. The second process intermediate was unstable in the reaction mixture, and required immediate isolation to avoid decomposition.

The Solution

To ensure the development of a safe and robust process, our PR&D team proactively resolved the process liabilities to support toxicology and phase 1 clinical supplies. Using STA's expertise in flow processing, a continuous stirred tank reactor-like (CSTR-like) process was developed. Chromium trioxide was successfully replaced with an alternative, environmentally-friendly oxidant. The Step 1 filtrate was telescoped directly into Step 2 and the second process intermediate was isolated promptly by filtration. As the stability of the isolated second process intermediate was acceptable, several batches were produced and combined to support the downstream chemistry requirements.

The Outcome

Our team developed a continuous processing solution to overcome inherent process liabilities and support production of > 100 kg of this key intermediate for our client.

responsive icon Reactor Range

Flexible state-of-the-art manufacturing assets consisting of 79 reactors ranging from 5 L to 5000 L, support projects from pre-clinical to pre-launch campaigns.

committed icon Experience

Our FDA approved kilo labs and pilot plants are well equipped and experienced to scale up all types of reactions producing grams to hundreds of kilograms of advanced intermediates and APIs.

managed icon 24/7 Operation

All of STA's manufacturing sites operate 24/7, with on-site process chemistry, engineering, quality and analytical support.

Innovate icon Fit for purpose

Our successful "Fit-for-purpose" process development philosophy reflects our appreciation of your needs at every stage of clinical development delivering optimal value and shortest lead times.

Building on the foundations of the WuXi business, we understand from personal experience what you need and expect from a service provider.

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