DoE Demystified

A series of posts going back to the basics of experimental design

Case Study 6

A Client observed a more than 10% of a high molecular weight impurity during the large-scale manufacture of an Active Pharmaceutical Ingredient (API). A Redox-Neutral Alcohol-Amine Coupling reaction was a potential alternative process replacing the SN2 displacement of a tosylate. The Redox Neutral coupling removes the Potential Genotoxic Impurity (PGI).

Case Study 5

A Client observed a new impurity doing a large-scale manufacture. Through a detailed understanding of catalytic mechanism, the root cause of the impurity formation was identified immediately. The theory was rapidly proven by small scale experimentation and a modified production procedure adopted to prevent any reoccurrence of the problem.

Case Study 4

A leading pharmaceutical company needed to manufacture 60kg of an active pharmaceutical intermediate using a Suzuki reaction. The catalyst for this particular process would have cost £240,000 and the previous manufacture unexpectedly afforded < 50% yield. We identified alternative robust reaction conditions which enabled the significant reduction in the catalyst loading reducing the catalyst cost of this process by more than £140,000 while reliably achieving more than 95% isolated yield. This case study demonstrates how the new reaction conditions were identified.

Case Study 3

A pharmaceutical company needed to manufacture 5kg of an active pharmaceutical intermediate using a Suzuki reaction. The reaction was low yielding (< 45%) with a very high catalyst loading. We identified a new, high yielding and robust process for the rapid delivery of 5 kg of the required API intermediate in 1 week by kinetic evaluation for this Suzuki reaction leading to understanding of reaction mechanism. This case study demonstrates how.

Case Study 2

A leading pharmaceutical company needed to manufacture 80kg of an active pharmaceutical intermediate using a Buchwald Hartwig amination reaction. The catalyst for this particular process would have cost $300,000. We identified alternative catalyst systems which reduced the catalyst cost of this process by more than $280,000. This case study demonstrates how the new catalyst system was identified by combining Design of Experiments (DoE) and Principal Component Analysis (PCA) in the development of catalytic reactions.

Case Study 1

A leading pharmaceutical company needed to manufacture 100kg of an active pharmaceutical intermediate using a Suzuki reaction. The catalyst for this particular process would have cost $500,000. We identified alternative catalyst systems which reduced the catalyst cost of this process by more than $400,000.

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