ChromXACT columns. GE Healthcare Life Sciences. General description. Focused functionality. Smart design. Contained packing

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1 GE Healthcare Life Sciences Data file AB Large-scale chromatography ChromXACT columns The ChromXACT platform consists of fixed-bed height chromatography columns specifically developed for standardized large-scale purification of biopharmaceuticals in a GMP environment. The robust columns are high quality options for cost-efficient purification processes. The ChromXACT column (Fig 1) has a sanitary, user-friendly design that allows easy handling, cleaning, and maintenance. A built-in swivel stand allowing easy maintenance is a key feature of the column. Other design features include an improved pack-in-place nozzle to simplify column operation and disposable bed supports that make cleaning operations easier and reduce risk of cross-contamination. The ChromXACT platform offers: Focused functionality Smart design for easy use and maintenance A viable option for GMP manufacturing General description ChromXACT columns are available in 400, 600, and 800 mm diameters and a variety of tube heights from 15 to 30 cm (see Ordering information ). The columns are pressure rated for operation at 3.8 bar (0.38 MPa, psi) and are intended for use with well-established GE Healthcare Life Sciences media (resins) such as the Sepharose Fast Flow and High Performance families. The range of column tubes enables tailoring of the columns to meet specific process requirements. Focused functionality Cost-effective process performance The novel design of ChromXACT columns is focused on the critical aspects of purification; non-essential components have been minimized, while ensuring effective chromatographic performance. The reduced number of components included in the columns enables easy and efficient packing, cleaning, and maintenance operations. Fig 1. ChromXACT columns for large-scale purification processes. Contained packing All column operations are performed in a closed system environment, resulting in less risk of the operator coming in contact with hazardous chemicals and of the target product being exposed to contamination. In this way, overall safety and hygienic operation are improved. Manual operations are simplified, and by following the general packing methods that come as part of the documentation with the column, reproducible column packing can be achieved. (for more information, study application note ). Smart design Simplified operation Once the column is assembled, no lifting gear is required for packing, operation, unpacking, or cleaning-in-place (CIP). As column operations are easily performed, this frees up resources and thereby simplifying large-scale operations.

2 SPI MP SPO PACK position When the nozzle is in the PACK position (middle position), the nozzle tip is halfway inserted into the column, allowing liquids or slurry to be pumped into the column through the slurry port inlet. MP = mobile phase inlet; SPI = slurry port inlet; SPO = slurry port outlet. Fig 2. The three positions of the ChromXACT nozzle when packing from the top. RUN position When the nozzle is in the RUN position, the nozzle tip is level with the bed support. The fluid path through the nozzle into the column is closed and the slurry will pass through the SPO. This position is used when filling the pack tubings and when establishing pack flow velocity prior to packing. This is also the position used during run as the mobile phase is accessible via MP. UNPACK position When the nozzle is in the UNPACK position, the nozzle is fully extended into the column. This position opens a passage behind the nozzle and liquid and slurry can exit the column through the slurry port outlet. Cleaning solution can be pumped through the nozzles and sprayed into the column. In this way, cleaning is easy and effective, with no need to dismantle the column. Distribution system The column features reliable and efficient distribution systems at both the top and bottom of the column. As the flow profiles are the same for both distribution systems, the column can be used in a bidirectional manner. Uniform mobile-phase distribution is further facilitated by the use of disposable bed supports of either 10 μm or 20 μm porosity. The choice of bed support is dependent of the mean particle size of the chromatography medium. Pack-in-place nozzles The ChromXACT column utilizes two simplified, manually operated, pack-in-place nozzles at the top and bottom of the column for packing and unpacking. The user-friendly design of the handles allows for smooth and easy nozzle control (Fig 2). The inner diameters of the various ports on the two identical pack-in-place nozzles are provided in Table 1. The ChromXACT column SPI and SPO nozzle ports have the same dimensions for all column sizes, whereas the MP port sizes are larger for larger diameter ChromXACT columns. Built-in swivel stand The change-over process when switching between column tubes is straightforward and can be easily performed by the operator or other production personnel with appropriate training. The ChromXACT column utilizes a practical swivel stand that facilitates the change-over process through simplified access to the bed support and meshes of the distribution system at the top of the column (Fig 3). The swivel stand also enables easy maintenance, such as the changing of seals, O-rings, and more. Table 1. Dimensions of the ChromXACT nozzle ports Nozzle port Inner diameter of port (i.d.) Connector size SPI 19 mm TC 50 SPO 22.1 mm TC 50 MP mm TC 25 MP mm TC 50 MP mm TC 50 Fig 3. The ChromXACT column features a swivel-stand design that allows easy access to bed supports and simplified maintenance AB

3 Principle of operation The ChromXACT column nozzles have three positions, which are set manually by means of a lever mechanism. The three positions enable packing, operation, and unpacking/cleaning to be performed. The ChromXACT column can be packed using a membrane pump or a dedicated packing station, together with appropriate accessories (see Ordering information ). Easy maintenance The pack-in-place nozzles and a decreased number of o-rings and seals in the ChromXACT columns allow for low maintenance cost. The swivel-stand design of ChromXACT columns (Fig 3) offers many practical advantages during maintenance, such as hoist-free handling and easy access to column tubes and disposable bed supports (Fig 5). Consistent performance Height equivalent to a theoretical plate (HETP) tests demonstrate consistent chromatographic performance with ChromXACT columns (Fig 4 and Table 2). Results from packed bed stability endurance tests show that the column performance remains good after prolonged use. Pack 1 Pack 2 Pack Absorbance (AU) Fig 5. The column can be lowered to allow removal of the column tube for maintenance or replacement Time (min) Fig 4. HETP tests on three different packs of DEAE Sepharose Fast Flow medium in a 400 mm, 20 cm column tube height ChromXACT column demonstrate consistency of chromatographic performance. Runs were conducted using a pulse injection of 0.1 column volumes of 2% acetone in water and an elution velocity of 30 cm/h. GE Healthcare service agreements are tailored to keep your column operating in good condition throughout the column lifecycle. Several preventive maintenance packages are available when purchasing the ChromXACT column. Contact your GE Healthcare sales representative for additional information. Table 2. Consistency of performance with the ChromXACT platform can be demonstrated using HETP tests with DEAE Sepharose Fast Flow medium and various combinations of ChromXACT columns and bed heights (results fall within the preassigned acceptance range) Column diameter (mm) Results Bed height (cm) Plates/m A s * Plates/m A s * Plates/m A s * *Peak asymmetry factor Scalability ChromXACT columns are designed with medium- to largescale production in mind. Scaling up a chromatographic process is easily performed with maintained reproducibility and convenience AB 3

4 Table 3. Weights, volumes, and dimensions of ChromXACT columns Description Max operating pressure (bar) Volume (L) Column tube height (cm) Weight, empty column (kg) Footprint (mm mm) ChromXACT to 37.7 Min. 15, Max. 30 Min. 120, Max ChromXACT to 84.8 Min. 15, Max. 30 Min. 233, Max ChromXACT to Min. 15, Max. 30 Min. 495, Max Customized solutions Column dimensions ChromXACT columns are available in three dimensions, 400, 600, and 800 mm (Table 3). The columns are designed and constructed around the same design principle. There are eight standard column configurations (see Ordering information ). Bed volume flexibility is achieved through column tubes that are available in 1 cm height increments from 15 to 30 cm. Packing equipment The column can be packed using separate membrane pump, pressure sensor, and flow meter. The ChromXACT columns can also be used with a packing station (Fig 6). Using a packing station makes column priming and packing a simple operation, reducing the operator s time to a minimum. For operation, packing stations only require a supply of compressed air. To select appropriate equipment for your set-up, see Accessories. Sanitary design One key aspect of GMP production is operation at hygienic standards. The design of ChromXACT columns allows operation at high standards of hygiene, and the efficiency of column sanitization has been investigated by microbiological challenge testing. A column packed with Sepharose Fast Flow medium was challenged with E. coli and incubated for 16 to 20 h at room temperature before being treated with 1 M sodium hydroxide (NaOH) and then sampled. The results show sanitization with 1 M NaOH to be effective. Despite the high levels of microbiological challenge, no challenging organisms were found after sanitization. Full study details are described in Application note: Sanitization of ChromXACT columns, GE Healthcare, , Edition AA (2013). Materials of construction ChromXACT column tube is made from acrylic and the disposable bed supports are constructed from polyethylene with 10 µm or 20 µm porosity (see Table 4 for a list of materials for column construction). The materials in contact with process fluid used in the ChromXACT column have been chosen for their biological and chemical compatibility with samples, buffers, and solutions normally used during column operation and sanitization procedures. These materials comply with USP Class VI as well as FDA 21 CFR Part 177 and are free from animal-derived components in compliance with EMEA/410/01 Rev 2. Table 4. Material of construction for ChromXACT columns Operating part Material Column tube PMMA*/Acrylic Bottom and top backing plate Stainless steel 316 Distributor PP Distributor meshes PP Support meshes PP Stream stoppers PP Mobile-phase tube PP Fig 6. A packing station such as the one illustrated above can be used with the ChromXACT column. For more details about set-up, please contact your local GE Healthcare representative. Bed support screw PEEK Bed support net PE O-rings EPDM and FEP** * PMMA = poly(methyl methacrylate); PP = polypropylene; PEEK = polyether ether ketone; PE = polyethylene; EPDM = ethylene propylene diene monomer; ** FEP = fluorinated ethylene propylene AB

5 Table 5. Chemical resistance of ChromXACT columns Chemical Conc. (% v/v) Time/cycle restrictions Comments 1-propanol 20% 1 to 16 h Bed support degassing/priming Acetic acid 25% 3 h CIP Acetone 2% 1 h Function test Ammonium sulfate 2 M 5 h Adsorption Ethanol 20% 12 mo and max 0.5 bar Storage Ethanol 70% 1 h Wiping external surfaces* Ethanol/acetic acid 20%/10% 3 h CIP Guanidine hydrochloride 6 M 5 h CIP Hydrochloric acid 0.1 M (ph 1) 1 h CIP Hydrogen peroxide 10% 1 h Fume, wiping external surfaces Isopropanol 10%/30% 1 h CIP Phosphoric acid 5% 16 h For passivation of stainless steel parts Per-acetic acid 4% 1 h Fume, wiping external surfaces Sodium chloride 0 to 3 M 3 h Purification, CIP Sodium hydroxide 1 M (ph 14) 24 h CIP Sodium hydroxide 0.01 M (ph 12) 12 mo Storage Sodium sulfate 1 M 3 h Adsorption Sodium hydroxide/ethanol 1 M/20% 3 h CIP Urea 8 M 5 h Purification, CIP Commonly used aqueous buffers for chromatographic use 10 to 250 mm ph 3 to h Equilibration, adsorption, elution *70% ethanol should not be used with acrylic surfaces, for example column tubes Chemical resistance Construction materials in the ChromXACT column are resistant to most chemical agents used in chromatography, including buffer solutions for adsorption, elution, and washing, and to solutions effective in cleaning, sanitization, and storage. Table 5 lists the general chemical resistance of the ChromXACT column. Documentation and support Comprehensive regulatory support documentation (EC declaration of conformity, material conformity, material certificates, production records) is provided with the column. Installation and operation qualification (IQ/OQ) packages are available as an option. Regulatory support documentation simplifies validation and thereby reduces start-up time, enabling the usage of the column in GMP production of biopharmaceuticals. The same level of documentation is available for all column sizes. To improve the handling and to maximize up-time on the ChromXACT column, a comprehensive solution suite including a thorough documentation package is available. The column comes with regulatory information, column operating instructions, general specification, site preparation guide, assembly drawings, and a spare part and accessory list. As an option, accessories, spare parts, and services (IQ/OQ, preventive maintenance packages) can be ordered. Installation and framework specifications ChromXACT column characteristics are listed in Table 6. Table 6. ChromXACT column characteristics ChromXACT 400 ChromXACT 600 ChromXACT 800 Load bearing (transportation) Max column weight* (kg) Column moved with forklift Min. space L H (mm) Load bearing (transportation) Max. column weight - not including accessory equipment (kg) Footprint L W (mm) Service access area L W (mm) * Empty column with 30 cm column tube height Minimum space requirements, including 10 cm clearance margins, when moving ChromXACT through doors, corridors, and elevators. Weight of packed column with 30 cm column tube height AB 5

6 Ordering information ChromXACT columns and column tubes: Standard configurations Column i.d /tube height ChromXACT 400 mm/15 cm ChromXACT 400 mm/20 cm ChromXACT 400 mm/25 cm ChromXACT 400 mm/30 cm ChromXACT 600 mm/15 cm ChromXACT 600 mm/20 cm ChromXACT 600 mm/25 cm ChromXACT 600 mm/30 cm ChromXACT 800 mm/15 cm ChromXACT 800 mm/20 cm ChromXACT 800 mm/25 cm ChromXACT 800 mm/30 cm For ordering other configurations, please contact your local sales representative. ChromXACT column tubes For buying additional individual column tubes, consult the table below: Column tube height i.d. 400 mm i.d. 600 mm i.d. 800 mm 15 cm cm cm cm cm cm cm cm cm cm cm cm cm cm cm cm Accessories Packing can be conducted using a packing station or a manual membrane pump. Recommended accessories and number of packs to be purchased for the two different packing setups are provided below. Item Units/ pack Number of recommended packs of each item Packing station Membrane pump 400 mm 600 mm 800 mm 400 mm 600 mm 800 mm Tie rod kits Tie rod kit, short for tube heights 20 cm Tie rod kit, long for tube heights > 20 cm Bed support tool* (for assembling/disassembling of bed support nut) Connectors Connector TC 25/i.d. 10 mm TC 25/i.d. 14 mm Connector TC 25/i.d. 10 mm TC 50/i.d. 22 mm Connector TC 25/i.d. 14 mm TC 50/i.d. 22 mm Flow meter Flow capacity appropriate for the pump flow rate, TC50-ports, 6 bar No available GE Healthcare product Media stirrer 150 mm Membrane valve Manual diaphragm valve i.d mm, 2 TC Manual diaphragm valve i.d mm, 2 TC MP tube support Nozzle o-ring mounting tool (for mounting of o-rings on nozzle tip) O-ring disassembling tools O-ring pick, plastic for o-ring removal O-ring removal tool Pallet lifter Min. lifting weight 800 kg. Min. lifting height 800 mm. Max. fork span 540 mm No available GE Healthcare product AB

7 Item Units/ pack Number of recommended packs of each item Packing station Membrane pump 400 mm 600 mm 800 mm 400 mm 600 mm 800 mm Pneumatic regulator Air filter regulator for membrane pump up to 100 L/min flow rate Air filter regulator for membrane pump up to 200 L/min flow rate Pneumatic connector kit Pressure gauge Pressure gauge, 0-6 bar, TC Pressure gauge, 0-6 bar, TC Rupture disc Rapture disc 4.2 bar, TC Rapture disc 4.2 bar, TC 50, i.d Rapture disc 4.2 bar, TC 50, i.d Shutter valve, 3 ports, 2-way Shutter valve, 3-port, 2-way i.d mm, TC Shutter valve, 3-port, 2-way i.d. 22 mm, TC Shutter valve, 4 ports, 4-way Shutter valve, 4-port, 4-way i.d. 10 mm, TC Shutter valve, 4-port, 4-way i.d. 20 mm, TC TC-clamp TC 25-clamp TC 50-clamp TC-gasket TC-gasket, i.d mm, TC TC-gasket, i.d mm, TC TC-gasket, i.d mm, TC 50 (For pressure gauge TC 50) T-junctions T-junction with short outlet i.d mm, 3 TC T-junction with short outlet i.d. 22 mm, 3 TC T-junction i.d mm, 3 TC Tool kit Tubing (PVC) with TC 25 connections Tubing i.d. 10 mm, 900 mm Tubing i.d. 10 mm, 1400 mm Tubing i.d. 10 mm, 1700 mm Tubing i.d. 10 mm, 2000 mm Tubing i.d. 14 mm, 750 mm Tubing i.d. 14 mm, 1800 mm Tubing (PVC) with TC 50 connections Tubing i.d. 19 mm, 900 mm Tubing i.d. 19 mm, 1400 mm Tubing i.d. 19 mm, 2000 mm Tubing i.d. 19 mm, 4000 mm Tubing (PVC) with TC 50 connections Tubing i.d. 25 mm, 900 mm Tubing i.d. 25 mm, 1400 mm Tubing i.d. 25 mm, 2000 mm Tubing i.d. 25 mm, 4000 mm Tubing (PTFE) with TC 50 connections Tubing i.d mm, 2000 mm Tubing i.d mm, 5000 mm Tubing holder (For upper SPI and SPO tubing) * A bed support tool is provided with each column at delivery GE Healthcare recommendation is to replace the entire nozzle available as spare part, see Operating instructions AB 7

8 Recommended packing station and pump for ChromXACT columns Item Units/ pack No. of recommended packs 400 mm 600 mm 800 mm Pump flow capacity (L/min) Required air supply (m 3 /min) Packing station Chromaflow packing station Pack Chromaflow packing station Pack Chromaflow packing station Pack Custom ordering Single pump Membrane pump (60 L/min) Membrane pump (100 L/min) Membrane pump (200 L/min) Related literature Application notes Sanitization of ChromXACT columns Packing of ChromXACT columns 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. Chromaflow and Sepharose are trademarks of GE Healthcare companies General Electric Company All rights reserved. First published Jun 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 AB 02/2014