Route Selection and Scale Up: Case Study and Exercise

Figure 1: SB 214857 (Lotrafiban) — **Figure 1:** SB 214857 (Lotrafiban)

This exercise will provide more information on scale up and why people make particular choices in an industrial setting. It will also explore how we move from a synthetic route that has been developed within medicinal chemistry to a route that is more productive, greener and has a higher throughput. In addition, it will provide an introduction to process safety and the things that you need to look out for when scaling up a chemical route; and good manufacturing practice (GMP). Whilst carrying out this exercise you will need to bear in mind the SELECT criteria.

The Scenario

Your company has started a clinical program looking at SB 214857 (Lotrafiban, figure 1) as a prevention for heart attack and stroke. You have scaled up the medicinal chemistry route, with a few modifications, to make multi Kg quantities of drug substance.

Planning for phase III studies, a demand of 3 tonnes (3,000Kg) of API is requested.

Do you stick with the current medicinal chemistry route and scale-up directly, or do you invest time and resource in a new route?