During target identification and validation, or even further along the journey in hit identification, medicinal chemistry can feel entirely divorced from process research and development, often with completely different organisations responsible for each.
And although in years gone by, staff might have had a mix of both on their CV, that is now becoming increasingly rare. But despite the gap, the two disciplines are very much linked on the path to clinical presentation, and engaging an integrated organisation that can take care of both will have significant benefits when it comes to keeping the development timeline on track. This means pushing a promising molecule along the line faster, with the result being higher product values, greater innovation and improved efficiencies.
Where do Medicinal Chemistry and PRD sit on the journey to clinical success?
Medicinal chemistry covers a great deal of the process of drug discovery, taking in those first steps from target validation through to hit identification, lead optimisation and ultimately candidate selection. Traditionally, process research and development (PRD) comes in once a candidate has been identified, and producing hundreds of grams for first pre-clinical use becomes the most pressing milestone.
Where does Medicinal Chemistry hand over to PRD?
Once the candidate(s) have been identified, being able to reliably produce the active pharmaceutical ingredient in sufficient quantity to fuel the development engine becomes the biggest barrier to progressing the molecule beyond the pre-clinical development phase. With an optimistic expectation of success in clinical studies, PR&D chemists will then work to devise a route that is suitable for large-scale manufacture of the API, where 10+ kg will be required.
What does PRD do that Medicinal Chemistry doesn’t?
While the medicinal chemistry route can sometimes be used for the first few hundreds of grams for pre-clinical studies, getting beyond that to the 10+ kg needed for clinical studies and beyond requires heavier-lifting PRD. With the correct analytical and process expertise, PRD will look to develop processes where throughput and yield are optimised, while side-products are identified and minimised. The laboratory setting that PRD teams work in can also respond to the need to solve process problems much more quickly than at plant, where costs are up to 15 times higher.
How can having one group work on both paths smooth the process?
With teams within one organisation working on both medicinal chemistry and PRD aspects, the unique demands and challenges of chemical development can be brought into focus much sooner than they might have separately. The early stages of research and development, for example, can be fed with advanced intermediaries using pragmatic adaption of chemistry from discovery. As well as this, new and improved methods can also be used when creating the first large batches of development materials, which is almost always time critical.
Where does using one integrated group take you that using separate teams won’t?
The benefits of smoothing the transition over a longer period are significant. In Europe at least, while many companies operating in the industry might have little crossover between these two areas, having the ability to have both in mind at the same time will result in greater innovation. Staff that have some experience in PRD can ensure that a molecule, and the documentation behind it, is in much better shape to smoothly progress beyond medicinal chemistry and incorporate process research and development ideas sooner rather than later. Inefficient chemistry can also result in up to 18 months of lost time and therefore slash new product value by as much as 30 per cent.