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A guide to drug discovery

Logistics of process R&D: transforming laboratory methods to manufacturing scale

Nature Reviews Drug Discovery volume 2, pages 654–664 (2003)Cite this article

Key Points

  • The means for achieving therapeutic goals resides in the active pharmaceutical ingredient of the drug used, and therefore there must be a manufacturing process capable of producing this valuable material in the quantity required, and with the high quality needed for human use.

  • The efforts required to achieve this are substantial, but, regrettably, not always seen in their full context; consequently, the challenges and frequent hardships involved are not fully appreciated.

  • This review analyses the role of process R&D in more depth, and gives some real-life examples of process development, with the aim of aiding the integration of process R&D with the rest of drug discovery and development.

Abstract

In the past, process R&D — which is responsible for producing candidate drugs in the required quantity and of the requisite quality — has had a low profile, and many people outside the field remain unaware of the challenges involved. However, in recent years, the increasing pressure to achieve shorter times to market, the demand for considerable quantities of candidate drugs early in development, and the higher structural complexity — and therefore greater cost — of the target compounds, have increased awareness of the importance of process R&D. Here, I discuss the role of process R&D, using a range of real-life examples, with the aim of facilitating integration with other parts of the drug discovery pipeline.

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Figure 1: Syntheses of acetylsalicylic acid, probably the first molecule of pharmaceutical importance to be submitted to proper process R&D.
Figure 2: Changing the perception of process R&D.
Figure 3: Bridging discovery and operations: process R&D contributions to pharmaceutical R&D along the time axis.
Figure 4: Illustration of the structural variation in active pharmaceutical ingredients.
Figure 5: Example of the variation in the price of active pharmaceutical ingredients.
Figure 6: Cortisone, and selected parts of the routes to its synthesis.
Figure 7: Example of a late-stage problem.
Figure 8: Example of the use of two different oxidants.

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Author information

Authors and Affiliations

  1. Process R&D, AstraZeneca, Södertälje, SE-151 85, Sweden

    Hans-Jürgen Federsel

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  1. Hans-Jürgen Federsel
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FURTHER INFORMATION

Encyclopedia of Life Sciences

History of drug discovery

Scientific Update

Organic Process Research & Development

Glossary

CHIRALITY

The geometric property of a rigid object (or spatial arrangement of points or atoms) of being non-superimposable on its mirror image.

RESOLUTION

The means applied to a racemic mixture to physically separate its constituent enantiomers.

ENANTIOMER

One of a pair of molecular entities which are mirror images of each other and are non-superimposable.

ENANTIOMERIC EXCESS

The percent excess of one enantiomer over the opposite enantiomer in a chiral sample.

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Federsel, HJ. Logistics of process R&D: transforming laboratory methods to manufacturing scale. Nat Rev Drug Discov 2, 654–664 (2003). https://doi.org/10.1038/nrd1154

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