Dirk Lütkemeyer: Platform Technologies
We are using platform technologies mainly for the purification of recombinant antibodies from mammalian cell culture. In developing the initial platform, we conducted a research project. Up to now we evaluated several different antibodies from CHO or hybridoma cell cultures. The biggest difference we saw was besides the characteristics of the different subclasses, the impurity profile which depended on the specific cell culture conditions that were being used.
With use of platform technologies, some conditions used in the process are standardized while others need to be customized. The conditions that are customized typically depend what is going on with the molecule in terms of the impurity profile, host cell protein, DNA, and aggregates. Steps are adjusted to minimize aggregation of the antibodies, for example, or to get better DNA or host cell protein removal.
In terms of adjusting conditions, we usually first focus on the elution profile. If that doesn’t work, we explore other buffer systems and then if necessary, try different chromatography media. We do evolve the platform. For example, if new chromatography media are available, we look to add to them to the platform.
We find that using platform technologies provides for a faster process development. The system also provides us with insights as to what are the crucial steps in the process. Sometimes a small change in just the buffer conditions has a big impact. The one caution when using platform technologies is to avoid forcing your molecule into the existing platform. It may be the case that better media or methods are available for a particular molecule, so avoid be locked in but rather find the best balance between use of the platform and new approaches when needed.