How do you design a safe and scalable synthetic route for your drug substance? | Quotient Sciences

During candidate selection, a chosen drug substance will typically have been prepared in only small quantities (up to a few grams) to support initial medicinal chemistry activities. The synthetic route used for this initial supply is rarely suitable for producing larger quantities of material for downstream development and will typically need to be modified, or sometimes redesigned entirely, to produce enough material for first-in-human (FIH) clinical trials.

At this point, there may be several challenges to address, such as:

• The existing route may rely on chemistry that is too hazardous to be performed at large scale, with reagents that are highly toxic, difficult to handle, or even explosive.
• It may rely on the use of solvents or reagents that generate hazardous waste or are discouraged due to environmental concerns.
• The starting materials may be expensive or difficult to procure in large quantities.
• Process impurities may be generated that are difficult to remove from the drug substance, and the existing synthesis might use purification methods (e.g. chromatography) that are impractical at large scale.
• The quantity of solvent used for a given reaction might result in poor throughput, meaning that many batches would have to be performed.

Quotient Sciences' Drug Substance Capabilities

Quotient Sciences , a drug development and manufacturing accelerator, works with clients of all sizes, from small biotechs to large pharma companies. We offer tailored services and integrated contract research and contract manufacturing solutions to help meet specific project goals.

Quotient Sciences provides drug substance synthesis and manufacturing capabilities from candidate selection through to commercial production. From our state-of-the-art facility in Alnwick, UK, we work with our customers to address complex challenges in drug substance development , including how to streamline drug substance manufacturing and how to successfully bridge into drug product development. Our experienced process chemists work alongside colleagues in analytical chemistry and material science to develop safe, scalable, and economical synthetic routes to achieve a suitable drug substance. Each cross-functional project team is overseen by a single project manager, who seamlessly manages the end-to-end process, provides regular status updates, and ensures timely project delivery for our customers.

Continue reading for more insight from our experts Paul Quigley , Principal Research Fellow, Drug Substance, and Richard Castledine , Head of PR&D, Drug Substance. You can also download our drug substance whitepaper to learn more about our capabilities.