New biopharmaceutical manufacturing facility
Construction complete in April 2005, validation completed by the end of 2005
Therapeutic proteins, Plasmid DNA, monoclonal antibodies
Boehringer Ingelheim Austria
Bia Separations, M+W Zander
Boehringer Ingelheim is one of the leading biotech companies in Europe and has consolidated this position in the last three years by constructing and opening a new biopharmaceutical plant at Biberach in Germany and now the expansion of their facility in Austria to double its previous capacity.
The Vienna facility is for the manufacture of therapeutically active proteins, plasmid DNA (pDNA) and single chain antibodies. The expansion of the Vienna facility has required a total investment of more than €80 million. It is the company’s largest single investment at its Austrian subsidiary and will create 200 new and highly qualified jobs in the Vienna region.
In 2004 the biopharmaceutical business achieved the highest growth rate, increasing net sales by 40%. In the last five years, sales in this area have more than tripled from €127 million in 1999 to €392 million in 2004. The expansion was planned in late 2003, construction started in early 2004 and the expansion was completed and inaugurated in April 2005.
BOEHRINGER INGELHEIM AUSTRIA
About 10,000m² of the Vienna plant is dedicated to biopharmaceutical production with a workforce of around 350 people. Fermentation processes can be optimised in various fermenters from 1L to 30L. Recovery and purifications are performed using state-of-the-art extraction, refolding, chromatography and filtration systems.
The facility has two independent fermentation plants with up to five fermenters. These range in size from 30L to 6,000L, giving a fermentation working volume on site of around 6,000L. In the extraction unit the tanks range in size up to 3,600L, providing flexibility to handle large-scale requirements during downstream processing. This facility also includes an explosion-proof area to handle processes using organic solvents.
The purification plant consists of five separate purification suites, varying in size from 24m² to 280m². Several units can be cooled, allowing downstream processing at 2°C to 8°C. The doubling of capacity in Vienna now enables the use of two 6,000L fermenters for biopharmaceutical production.
Lorenz Consult was the architect, designer and planner for the new expansion at the Vienna site. M+W Zander were the engineers and project managers for the project and were able to fully coordinate the construction of the new biopharmaceutical manufacturing capacity in Vienna. BIA Separations d.o.o., Slovenia, have contributed new technology to the production process for pDNA utilising state-of-the-art technology.
The process employs high cell-density fermentation achieving high titres of up to 1g pDNA per litre, followed by a powerful downstream separation process utilising Convection Interaction Media (CIM) technology to produce pDNA of greater than 99% purity with very low levels of endotoxin and genomic DNA. The use of CIM technology during downstream processing eradicates the need for precipitation or extraction of the pDNA using toxic organic solvents or animal-derived enzymes. In addition, analytical methods have been developed for both in-process control and drug substance release that can detect all forms of DNA and potential impurities, thus ensuring the safety and quality of the product.
Boehringer Ingelheim developed the CIM Technology in conjunction with BIA Separations and will now offer the technology as a Contract Manufacturing Organisation (CMO) service to customers worldwide. The company has established itself as the leading industry participant currently capable of producing pDNA on a large scale, and at current Good Manufacturing Practice (cGMP) compliant levels. With gene therapy set to produce the next generation of blockbuster drugs, Boehringer Ingelheim is ideally positioned as the CMO for the production of these drugs for therapeutic purposes.
CIM COLUMNS AND BIA SEPARATIONS
BIA Separations is the only worldwide manufacturer of short monolithic columns optimised to meet the research and production needs of the biotechnology industry. CIM are the first monoliths used for the industrial-scale purification of proteins, DNAs and virus particles.
CIM tube monolithic columns are large-scale forms of CIM supports intended for laboratory, semi-industrial, and industrial scale purification and bioconversion. A tube geometry optimised for radial flow of the mobile phase is an advantageous and efficient scale-up strategy designed for powerful biochromatographic separations.
The tube geometry assures a reproducible and uniform flow profile through the monolith due to the flow-unaffected hydrodynamic characteristics of monoliths. The thickness of the tube does not influence or decrease the separation power of the column despite an increase in the linear velocity from the outer part of the tube toward the inner part. The design of the housing forces the liquid to flow in a radial direction.
The mobile phase entering the tube monolithic column is directed into a helical groove drilled inside the body of the housing, which distributes the mobile phase over the entire outer surface of the monolith. The construction of the helical groove is such, that the mobile phase is forced through the porous monolithic annulus and into the hollow centre of the tube. This central hole collects the mobile phase from the outer surface of the CIM tube. The actual separation process takes place at the point where the sample flows through the wall.
The CIM tube monolithic columns have a low dead volume, excellent sample distribution and simple handling and can be easily connected to any LC/HPLC system by using suitable connectors.