Large-scale chromatography is often the only solution to the purification of valuable drug compounds in the pharmaceutical industry. For many manufacturers, bespoke chromatography solutions seem the simplest
and most efficient way of implementing such techniques, utilizing the specialist knowledge of in-house chemical engineers to create a custom solution. However, there are numerous drawbacks to such an approach.
In many cases, a commercially available purification system specifically designed for a manufacturing environment represents an attractive alternative....
In this project, CordenPharma Switzerland evaluated Biotage® Flash 400 and pre-packed cartridges alongside a custom-made alternative as part of a plan to increase the efficiency of the workflow. The purification itself was of a large
multi-Kg batch of crude API (the nature of the API is proprietary).
The existing process metrics using a filter apparatus (Figure 1) was as follows:
- Process consisted of 5 runs with ca. 4 – 7.2 kg crude/ run; including a requirement for re-chromatography of any incompletely purified batch
- The time needed for ~41 kg crude would be around 18 days of operation including column packing /unpacking
- The yield was 18.6 kg (73.8%),which proved to be 88.9% pure by HPLC-UV.
Figure 1. (Original process) - Repurposed filter for purification chromatography.
Although original results were reasonable, the process was still an expensive component of the overall workflow, and maintenance of the filter equipment could be time consuming. So an alternative method was sought using a commercially-available system.
Figure 2. Biotage® Flash 400 system incorporated in a custom process workflow for efficient purification chromatography at CordenPharma Switzerland.
Speaking about Biotage Flash 400, the team at CordenPharma noted that the system offered several advantages over bespoke in-house solutions:
» The system is designed to fit into a family of instruments with common media types, meaning that scale-up processes are simpler and more robust.
» Designed specifically for the manufacturing environment, so for example ATEX explosion-proof rating is designed into the system, as are ways of pumping solvent and handling the stationary phase media.
» Expertise in implementing such a solution is provided by the supplier.
» Service support is assured, so that expensive system downtime is minimized.
» Silica media is supplied in pre-assembled cartridges, for easy storage, use and disposal (especially important in projects using HP-APIs).
This made for a much more commercially viable solution and implementation of the Flash 400 system helped save 13 days in operator time, increased chemical yields over 15% whilst also reducing process operating costs by 50%.
Click below to read to full story and see the detailed process metrics.