Case Study: Development and GMP Manufacture of a Polymeric Conjugate Including a Potent, Controlled Substance

Challenge

Transfer and optimize a multistep synthesis for a novel API based on the introduction of a polymeric conjugate to a potent, controlled substance and generate sufficient material for both pre-clinical and clinical trials within a very aggressive timeframe and budget.

Accomplishment

Cedarburg Hauser successfully developed, optimized, scaled and manufactured a potent, controlled substance polymeric conjugate API. Working closely with our client we were able to meet their aggressive timeline and generate 1.3 kg of the target API conjugate under GMP conditions for their clinical trials. The material was high purity and the final optimized process produced an overall yield of 52%.

Why Cedarburg Hauser was Selected

Cedarburg Hauser’s prior experience working with potent and controlled substances, our flexibility and our ability to meet tight timelines made us the right partner for this project. Our experience brought several important advantages to the project including

• The scientific expertise related to conjugating potent and controlled substances to polymeric compounds.
• The scientific expertise with potent and controlled substances required to successfully complete the challenging process chemistry, optimization and scale-up.
• The proper controls were already in place for handling, monitoring and storage of the controlled materials.
• The appropriate training and laboratory controls for safe handling of the potent materials.

Details

The API, along with several of the intermediates, was a potent and controlled substance requiring special handling and documentation. Cedarburg Hauser’s chemists were able modify the chemistry from the client’s original gram scale synthesis to make it amenable to scaling (> 1 kg) by reducing reaction volumes and replacing expensive solvents.

The final product was originally a tacky, waxy solid that was difficult to handle. Through process development, Cedarburg Hauser’s chemists were able to develop an isolation procedure that produced the API as an easily filterable solid that was also simple to handle.

Additionally, Cedarburg Hauser’s analytical team developed and qualified methods to monitor both reaction progress and intermediates, ensuring a high purity for the final API, which exceeded the customer’s expectations.

Working closely with the customer we were able to meet their aggressive timeline to generate 1.3 kg of the target API under GMP conditions in high purity with an overall yield of 52% for 5 steps.

Contributing Scientists

Learn more (educational background, work history, past projects, patents and publications) about the scientists at Cedarburg Hauser that led this project.

Cathy Smith, PhD – Senior Scientist