Increasing diversification of the type of drugs in biopharmaceutical pipelines together with increasing number of candidates that needs to be evaluated require the development of novel high throughput formats. For producing candidates in sufficient amount and purity in a short time, magnetic beads based purification offers the ability to avoid costly and time-consuming filtrations and can also easily be run in parallel. Most commercially available magnetic particles are in the sub-micron range in diameter, which leads to high binding surface area and high binding capacities. However, these small sized particles are not easily controlled in a magnetic field and difficult to handle in larger scales.<br/><br/>We have developed novel agarose based magnetic beads with sizes of 10-100 µm. The beads have a large amount of magnetite incorporated and are compatible with large scale manufacturing methods. The size makes them easy to handle and the magnetite amount makes these particles highly responsive and readily captured by a magnetic field. No loss of beads between process cycles has been observed. We have explored the use of these magnetic beads in combination with specific affinity ligands binding to the target biomolecules in crude cell cultures or cell lysates, showing that direct capture and isolation of the target from the crude feed is possible even in liter scale volumes. Our case studies focus on semi-large scale direct capture of therapeutic proteins (mAbs and antibody fragments) and shows that purity and yield are not compromised. We will also present how the bead design is affecting the performance. By capturing the target biomolecules directly from the crude feed, several clarification and purification steps such as centrifugation, filtration and capture chromatography can potentially be replaced by one single step. In conclusion, the combination of affinity ligands with magnetic bead resin technology leads to dramatically shorter process times and cost savings. This technology has great benefits in the early stage of drug discovery when large number of drug candidates needs to be screened and purified in a short time.<br/>

Integrated clarification and purification of biomolecules in semi-large process scale using magnetic bead technology

2019 Spring National Meeting

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