The purification of biopharmaceuticals from large amounts of crude feedstock and natural sources like blood by conventional chromatography is often limited. Competing protein concentrations of over 50 g/l combined with high concentrations of particulate contaminants in the feedstock cause long processing times and pore plugging. Multistep pretreatments are essential in order to overcome these limitations. However, pretreatments such as the frequently used Cohn process from the 1940s cause high costs for explosive proof installations, waste treatment and the risk of irreversible protein degradation. Due to these reasons, there is great demand for direct capturing unit operations for the purification of high-value proteins from a vast variety of crude, unfiltered biological liquors deriving from natural or genetically engineered feedstock.<br/>Integration of solid-liquid separation and purification steps leads to reduced processing times, higher yields and improved process economics. For this purpose we developed a “fit-for-purpose” cGMP compliant automated magnetic separation device in close cooperation with the company KMPT Andritz. There is no such equipment available on the marked jet. The separation device is based on the High Gradient Magnetic Separation principle and applies a “rotor-stator” approach for improved cleanability. A Consequent re-engineering was required to meet hygienic design and GMP standards. The combination of the cGMP magnetic separator with magnetic particles, functionalized with high affinity ligands, leads to a new approach of integrated downstream processing. We show a fast and easy purification process for Gonadotropin from pregnant mare serum, including an optimized batch process approach, enabled by an automated process controlling. The optimized batch adsorption approach leads to a significant increase in yield and overall process economy.<br/>The multiple use of the magnetic particles will be discussed including the cleanability and the influence of a CIP protocol on the binding behavior.<br/>As important is the development of an appropriate cleaning protocol and cleaning validation for the separator itself.<br/>We will show an optimized cleaning protocol for the magnetic separation device and validate a direct surface swabbing test analyzed by a total organic carbon analysis.

Fit-for-purpose cGMP compliant magnetic separation device: Cleaning validation and protein purification results

253rd National Meeting (2017)

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