Manufacturing Solutions to enhance filtration and chromatography productivity

Transcription

1 Manufacturing Solutions to enhance filtration and chromatography productivity Biopharmaceutical process development and manufacturing are facing significant increases in R&D costs together with longer development times for new drug candidates. These costs and time losses, due to bottlenecks during scale-up, can be reduced by increasing the number of automated steps in the workflow and improving handling. 7

2 Fig 1. UniFlux integrated tanks allow automated cross-flow filtration with UNICORN system control. GE Healthcare constantly strives to develop products and services to remove obstacles in largescale manufacturing processes. Our Manufacturing Solutions platform is designed to speed up and facilitate filtration and chromatography steps of process workflows and hence remove potential delays in manufacturing. The Manufacturing Solutions platform currently includes filtration control with UniFlux systems and UNICORN software, easier chromatography media handling using Media Wand and slurry tanks, automated column packing with AxiChrom columns, and chromatography control with ÄKTAprocess and UNICORN software. On the following pages, we highlight recent additions to the Manufacturing Solutions platform, all designed to cut lead times, increase automation, enhance operator safety, and improve operational efficiency and overall process economics. UniFlux filtration systems now with integrated recirculation tanks UniFlux is a line of cross-flow filtration (CFF) systems that utilize UNICORN software for full automation with data logging capabilities over the entire cross-flow process. The systems are intended for pilot- through production-scale biological separations. They are configured to operate hollow-fiber cartridges for microfiltration applications such as cell clarification/harvesting, or cassettes/hollow fibers for ultrafiltration applications, such as protein concentration and diafiltration in downstream unit operations. Cross-flow filtration processes require a tank to feed the filter and to collect retentate. The tank is a vital component of the system and plays a major role in mixing, measurements, and minimizing recirculation volume. When running automated CFF, a tank requires system control in order to enable a fully automated process. 8 Upstream and Downstream Issue 3

3 GE Healthcare now offers a series of integrated tanks that communicate with UNICORN, allowing fully automated control of the tank sensors and mixer. Weight and volume in the tank are also monitored via UNICORN, allowing for control of concentration or diafiltration. The tanks are designed to work seamlessly with UniFlux systems to ensure a total CFF process. They are available in a range of sizes from 5 and 10 l capacity for UniFlux 10 System to 600 l capacity for UniFlux 400 System. All tanks are available with a large range of options including sensors, valves, mixer, cooling jackets, and hoses. UniFlux tanks are constructed from stainless steel and are mounted on a skid with castors, allowing for easy movement for storage, installation, cleaning etc. The smaller 5 and 10 l tanks suitable for UniFlux 10 are mounted directly on the system skid. Slurry tanks improving process simplification and economy GE Healthcare has developed a range of slurry tanks designed to operate seamlessly with our series of chromatography systems and columns. Slurry tanks assist in generating a homogenous slurry and thus play a critical role in ensuring a well-packed column and utilization degree of the chromatography medium. A well-packed column is characterized by high resolution and high bed stability, characteristics that help to avoid costly repacking due to poor HETP and asymmetry. Slurry tanks enable the generation of an even particle size distribution throughout the slurry in a gentle manner and thereby the tank prevents exposing the chromatography medium to excessive shear forces that can lead to degradation, which results in clogged nets and increased back pressure. Slurry tanks also support a range of additional process steps when packing and unpacking chromatography media. The ability to transfer media/buffer via pressure/vacuum results in time and material savings, as well as improved operating conditions. The tanks are composed of stainless steel tubing and piping with EPDM gaskets, and are pressure rated to 4 bar g. A control panel on the front of the tank simplifies operation and enhances operator safety and a manhole cover allows easy access to the interior from the top of the tank (Fig 3). Tanks are available in sizes from 500 to 2000 l and with a number of options including load cells, air blow/buffer drain, pressure/vacuum function, and a sample valve. Fig 2. A 1600 l slurry tank is easily moved for simplified and safer packing and unpacking of chromatography media. Fig 3. Slurry tank top. Inline conditioning improving the buffer preparation step in purification Current trends in manufacturing biopharmaceuticals have put demands on securing increased buffer supplies delivered at precise times and at correct concentration/ph/ conductivity and flow rates. Major challenges in downstream processing today are buffer preparation and usage due to the increased titers and volumes of product to purify and the use of hold-up tanks for products in between purification steps. Modern technologies such as Inline Conditioning have gained increased interest, not only because they reduce the need for large storage tanks, but also because Inline Conditioning can deliver correct buffers and solutions for a specific process need at a lowered total cost of ownership. GE Healthcare has used its long experience in the chromatography field to develop a quality system for Inline Conditioning. Inline Conditioning functionality can be included in both chromatography and filtration systems. 9

4 Advantages of Inline Conditioning Apart from timely buffer delivery, Inline Conditioning conveys a range of advantages including increased reproducibility due to automation, and use of smaller tanks or disposable bags. Buffers are delivered from concentrates at the exact point of use in the process. Inline Conditioning minimizes waste, saves time, and reduces the amount of floor space used. Another advantage of Inline Conditioning is that by including the buffer preparation within the chromatography/filtration run, all relevant data for buffer characteristics and for the run itself are recorded by the UNICORN control software at the same time, resulting in one batch record for both operations. The intelligent control strategy of Inline Conditioning for chromatography/filtration systems allows automatic adjustment of prepared buffers, thereby improving the quality of the process. System requirements Inline Conditioning is a solution for process engineers who need to mix different buffers and solutions before loading them onto a chromatography column. Automation is achieved by using our proprietary Programmable Logic Controller (PLC) incorporated in the UNICORN control software, independent of system configuration complexity. Optional organic solvents on one or several inlets ms/cm Acid/Acid component Base/base component Water Salt Optional inlets P1 P2 P3 P4 P5 Cond UV ph Cond UV ph Prepared buffer to column Fig 4. scheme showing a typical system setup for Inline Conditioning. Mixing area: 600 l/h 280 l/h ph The use of gradient systems such as ÄKTApilot or ÄKTAprocess is crucial for best mixing effects and reproducible results using Inline Conditioning. A typical Inline Conditioning design is shown in Figure 4. After discussion with the customer, GE Healthcare designs made-to-order hardware that enables Inline Conditioning functionality on different systems. Inline Conditioning fuctionality ensures best performance and system configurations with the smallest possible footprint min Fig 5. Example of an Inline Conditioning run in UNICORN. The green curve is the flow rate, with set values at 600 l/h and 280 l/h, respectively as indicated by the text above. The blue curve is conductivity and the red curve ph. 5 4 Efficient buffer prep from stock solutions The Inline Conditioning system can be used for automatic inline conditioning from concentrated stock solutions. This was demonstrated by using the system to prepare a range of the most commonly used buffer systems in biopharmaceutical production of MAbs. Figure 5 shows an output plot from an Inline Conditioing run mixing 30 mm of sodium phosphate buffer, ph 6.5 from 0.4 M stock solutions in UNICORN. Two flow rates were employed: 600 l/h and 280 l/h. In this case, steady state was achieved in less than 1 min at both flow rates, which demonstrates the reliability of the Inline Conditioning setup for automated buffer dilution from concentrated stock solutions. Manufacturing perspective Using only one or two buffer systems in manufacturing can lead to significant savings in raw material and equipment costs, as well as a reduced need for storage space. However, a balance has to be struck between such savings and the potential impact on process robustness and yield vs. contamination profile. This approach requires a well-documented design space and process analytical technology tools to enable adjustments of the process. The Inline Conditioning solution allows biopharmaceutical producers to explore these possibilities using a system test rig for prepurchase mixing studies. Further information Data files Media Wand Media Handling Unit, Code no UniFlux System, Code no Slurry tanks, Code no Inline conditioning for process chromatography systems, Code no Web Upstream and Downstream Issue 3

5 GE Healthcare Life Sciences For local office contact information, visit GE Healthcare Bio-Sciences AB Björkgatan Uppsala Sweden imagination at work GE, imagination at work, and GE monogram are trademarks of General Electric Company. ÄKTA, ÄKTAcrossflow, ÄKTApilot, ÄKTAprocess, AxiChrom, Biacore, BioProcess, Capto, Cellbag, Cytodex, HiPrep, HiScale, HiScreen, HiTrap, MabSelect SuRe, Media Wand, PreDictor, ReadyMate, ReadyToProcess, Sepharose, UniFlux, UNICORN, and WAVE Bioreactor are trademarks of GE Healthcare companies. Any use of UNICORN software is subject to GE Healthcare Standard Software End-User License Agreement for Life Sciences Software Products. A copy of this Standard Software End-User License Agreement is available on request. Capto ViralQ: Separating viral particles with Capto Q products may require a license under United States patent number 6,537,793 B2 and equivalent patents and patent applications in other countries owned by Centelion SAS. Such a license is not included with the purchase of Capto Q but is included with the purchase of Capto ViralQ products. With the purchase of Capto ViralQ the customer is granted a free limited license under US patent 6,537,793 B2 and equivalent patents and patent applications in other countries owned by Centelion SAS to separate viral particles solely through use of the product purchased. Protein A: GE Healthcare shall upon REPLIGEN S request in any advertising, promotional or sales literature regarding Licensed Products indicate that GE HEALTHCARE has a license under the patent rights from REPLIGEN. ReadyMate: This product is covered by US patent number 6,679,529 B2 owned by Johnson & Boley Holdings, LLC and licensed to GE Healthcare companies. Ni Sepharose 6 Fast : US patent numbers 5,284,933 and 5,310,663, and equivalent patents and patent applications in other countries (assignee: Hoffman La Roche, Inc) relate to the purification and preparation of fusion proteins and affinity peptides comprising at least two adjacent histidine residues (commonly known as the histidine-tag technology). Any customer that wishes to use Chelating Sepharose Fast, Ni Sepharose 6 Fast or IMAC Sepharose 6 Fast for non-research/ commercial applications under these patents is requested to contact Hoffman-La Roche AG, Corporate licensing, attention Dr Andreas Maurer, CH-4070 Basel, Switzerland, telephone , fax , for the purpose of obtaining a license. All third party trademarks are the property of their respective owners General Electric Company All rights reserved. First published Nov All goods and services are sold subject to the terms and conditions of sale of the company within GE Healthcare which supplies them. A copy of these terms and conditions is available on request. Contact your local GE Healthcare representative for the most current information. GE Healthcare UK Limited Amersham Place Little Chalfont Buckinghamshire, HP7 9NA UK GE Healthcare Europe, GmbH Munzinger Strasse 5 D Freiburg Germany GE Healthcare Bio-Sciences Corp. 800 Centennial Avenue, P.O. Box 1327 Piscataway, NJ USA GE Healthcare Japan Corporation Sanken Bldg., , Hyakunincho Shinjuku-ku, Tokyo Japan AA 11/2010