Scientists at Batavia Bioservices BV have developed and optimized over 200 chromatography processes based on Simulated Moving Bed (SMB) and other multicolumn chromatography Technologies. Multicolumn chromatography and SMB Technology allow for significant savings in chemicals consumption and in the installed volume of stationary phase (chromatographic medium or resin).

Scientists at Batavia Bioservices B.V. have experience with all types of SMB Technology that are commercially available and have developed proprietary software products for design and simulation of these types of processes. These software products provide tools to enhance process understanding and allow for a quick and reliable optimization results.

Scientists at Batavia Bioservices B.V. are permanent invited guest lecturers at various international post-graduate courses and international conferences. The company provides services in simulation of SMB processes and actual lab scale SMB runs.

Case study 1

Most modern production methods for vitamin C (ascorbic acid) involve two ion exchange conversion steps. These steps are performed at very highly concentrated solutions and hence a batch process is very inefficient.

Batavia Bioservices has transformed these ion exchange steps into a continuous ion exchange process on a carrousel type SMB system for one of its customer’s, an undisclosed pharmaceutical company. Proof of principle was delivered in a 20-column laboratory scale unit with 4 litres of ion exchange media. The results indicated a significant improvement in specific productivity and large savings in the consumption of water and chemicals. From these results, the process was scaled up to two 30-column ion exchange systems with over 80 m3 of ion exchange resin each. This process has been implemented at various other pharmaceutical companies since then.

Case study 2

After a few years on the market, an undisclosed manufacturer launched a development program aiming at a rigorous cut in the cost-of-goods. Elimination of several unit operations in the upstream process enabled this target and significantly reduced product loss, at the cost of a drastic change in impurity profile compared to the original set-up.

Batavia Bioservices was requested to improve the separating power of the SMB over tenfold to provide the same yield and quality as the original process. The combination of data mining and column tests gave way to simulation studies which in turn revealed that target yield and purity could be achieved by implementing a moderate change in the process configuration. These results have been confirmed in pilot studies using a small-scale carrousel-type SMB system and were successfully implemented in large scale commercial production.

Case study 3

For a food processing company a novel multicolumn chromatography process was developed for the recovery of a native protein from a potato fruit juice. In this process the concept of simulated moving bed technology was combined with expanded bed chromatography. The basic chromatography process was developed on a batch EBA column and translated into a multicolumn chromatography process.

The new process, designed by scientists working at Batavia Bioservices, was evaluated in a custom-designed pilot plant with columns of 10 cm inner diameter. This system provided proof of principle and demonstrated robustness of the process over a long period of operation. Simultaneously, a dedicated SMB system was designed and built for early stage production purposes. This system was taken in operation in 2007 with six columns, each holding between 200 and 600 liter of chromatography media. This unit has a capacity in the order of 100 kg purified protein per day.

Relevant References:

M. Bisschops and M. Giuseppin (2007) EP 1994972; M. Bisschops et al.(2008) “Continuous Recovery of Proteins using Large-scale Multicolumn EBA Chromatography Technology”, Poster at Recovery XIII, Quebec City (Canada)

R. de la Fuente, M. Pennings and M. Bisschops (2007) “Continuous Multicolumn Ion Exchange for Vitamin C Production”, Poster presented at EFB Workshop on Downstream Processing, Delft (NL)