3M Emphaze. AEX Hybrid Purifier. 3M Innovation. Transform and Redefi ne. Effi ciency. Purity. Economics. 3M Purification

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1 3M Purification Single-Use Clarification and Purification for Biopharmaceutical Processes 3M Emphaze AEX Hybrid Purifier 3M Innovation. Transform and Redefi ne. Effi ciency. Purity. Economics. The 3M Emphaze platform represents a new class of purifi cation products that can redefi ne the manufacturing processes for the production of therapeutic proteins and other biologics.

2 3M Innovation: Making Progress Possible 3M creates transformational products and solutions that enable customer successes and improve people s lives around the world. We utilise a collaborative, high-energy approach to solve the toughest problems across industries and markets by: Constantly exchanging and building on each other s ideas. Uncovering new connections between seemingly unrelated markets and more than 5 diverse technology platforms. 3M Advancing the Biopharmaceutical Industry At 3M, we are advancing the global pharmaceutical industry by helping to build products that enable better and more efficient manufacturing processes. 3M Purification provides cutting-edge technologies to address filtration and purification needs of the global biopharmaceutical industry. We deliver novel products to enable reduction in the complexity and cost of pharmaceutical, vaccines and plasma fractionation production processes. Fostering a culture of intellectual curiosity and creativity that pushes boundaries. Transforming 2 Ideas into Realities.

3 3M Emphaze AEX Hybrid Purifi er The 3M Emphaze AEX Hybrid Purifi er combines advanced polymer materials, a novel anion exchange hydrogel nonwoven media integrated with a fi ne particle, bioburden reduction multi-zone membrane. Ab Abrasives Ac Acoustics Ad Adhesives Am Advanced Materials An Analytical Bi Bi Biotech Ce Ceramics Dd Drug Delivery Di Display Do Dental and Orthodontic Materials Em Electronic Materials Es Electronics and Software Fc Flexible Converting and Packaging Fe Flexible Electronics Fi Films Fs Fs Filtration, r tion, Separation, Separation, Purification Purification Im Imaging Is Integrated Systems and Design Lm Light Management Me Metal Matrix Composites Mf Mechanical Fasteners Mi Microbial Detection and Control Mo Moulding Nt Nanotechnology Nw Nw Nonwoven Materials Nonwoven Materials Op Mr Microreplication electronics Opto- Pd Particle and Dispersion Processing Po Pm Polymer Melt Processing Po Porous Porous Materials & Materials Membranes and Membranes Pp Precision Processing Pr Process Design and Control Rp Radiation Processing Sm Specialty Materials Su S Surface Modification Modification Tt Track and Trace Vp Vapour Processing We Accelerated Weathering As Application Software Ec Energy Components Fl Fluoromaterials In Inspection and Measurement Md Medical Data Management Pe Predictive Engineering and Modelling Se Sensors Wo Wound Management Unique 3M Technology The 3M Emphaze AEX Hybrid Purifier is created using the unique combination of numerous 3M proprietary technologies. The resulting product provides an extremely high level of product protein purity early in the downstream process. The 3M Emphaze product platform demonstrates that 3M s materials-based technology engine enables true innovation for the Biopharmaceutical industry. The 3M Emphaze AEX Hybrid Purifier combines advanced polymer materials, a novel anion exchange hydrogel nonwoven media integrated with a fine particle, bioburden reduction multi-zone membrane. 3

4 Transforming the Biopharmaceutical Production Process: Efficiency. Purity. Economics. The 3M Emphaze AEX Hybrid Purifier represents a new class of clarifying products that can be applied to redefine your manufacturing processes for the production of therapeutic proteins like monoclonal antibodies (mab), blood proteins and vaccines. 3M Emphaze AEX Hybrid Purifier, the first in a series of chromatography and membrane chromatographic products, is designed to remove insoluble and soluble impurities, like cell debris, aggregates, bacteria, DNA, HCP and virus, which helps optimise downstream processes. Through a unique combination of 3M technologies, 3M has created an encapsulated, singleuse all-synthetic clarifying media based on a hydrogel nonwoven media. The 3M Emphaze AEX Hybrid Purifier delivers clarified process fluid by removing insoluble impurities, such as cell debris, aggregates and bacteria, through a combination of chromatographic and size exclusion mechanisms. When used at the clarification stage, the matched component combination of 3M Emphaze AEX Hybrid Purifier, Zeta Plus depth filters and LifeASSURE membrane filters provide a process with increased efficiency and protein purity. This can enable the reduction of substantial biopharmaceutical manufacturing costs. Making Your Job Easier Increased Process Efficiencies Simplifying our customers processes by removing multiple types of impurities in a single process step, leading to a better process economics. As a matched component solution, 3M s Zeta Plus Series depth filter, Emphaze AEX Hybrid Purifier and LifeASSURE membrane filters can eliminate the need for the centrifuge unit operation and also reduce the required area of the downstream sterilising-grade membrane. Increased Product Purity and Yield Removing impurities early in the process, the 3M matched component solution provides protection to chromatography columns increasing their purification performance. Simplified Manufacturing Process Elimination or optimisation of unit operations results in significant manufacturing operational efficiency improvement. Significant biopharmaceutical process-wide improvements are achieved when deployed at the clarification stage of the monoclonal antibody purification: High performance clarifi cation Enables higher Protein A column performance Enables tighter sterilising filters with less surface area Enables smaller downstream AEX column Nominal 3% HCP and greater than 4 log DNA reduction Consistent output turbidity (< 5 NTU) Tight particle size cut-off (<3 nm) Greater than 6 log bioburden reduction > 1x less HCP in the product stream post Protein A > 1x reduction in DNA concentration post Protein A > 1x less residual contaminants on Protein A column Reduced column capacity fade and potentially extended column life Seamless.2 μm to.1 μm transition Signifi cant reduction in filter surface area > 1x less contaminants Target protein at or near regulatory HCP and DNA contaminate purity requirements 3M Emphaze AEX Hybrid Purifi er 4

5 3M Emphaze AEX Hybrid Purifi er Unique Product. Unique Construction. The 3M Emphaze AEX Hybrid Purifier is an integral combination of two types of purification media that work together to provide high product purity in a single unit operation. The all-synthetic purification media and unique layering construction provides high purity by integrating multiple separation mechanisms into one single-use product: 4 layers of Q-functional Nonwoven Media Nonwoven Media Layer 1 Layer 2 Layer 3 Layer 4 Strong anion exchange chromatographic media, comprised of a hydrogel nonwoven, provides high removal of insoluble and soluble impurities such as cell debris, aggregates, bacteria, DNA, HCP and virus. Highly Asymmetric.2 μm Bioburden Reduction Filter The unique combination of a highly asymmetric 9 zone microporous membrane along with the highly charged hydrogel media provides a substantial reduction of negatively charged soluble impurities, including microbiological contaminants. Bioburden Reduction Membrane Zone 1-3 Zone 4-6 Zone μm Each zone and layer of the membrane has a progressively smaller pore size allowing both high purity and high throughput early in the downstream process. Fine particle removal that exceeds the performance of a.2 or.1 grade micron membrane alone. Superior turbidity (particle) removal: <5 NTU. > 6 log bioburden reduction. Even flow distribution. Anion Exchange Anion Exchange Significant polymer chemistry development to create a highly-charged, durable polymer for reduction of negatively charged insoluble and soluble impurities including cell debris, aggregates, bacteria, virus, endotoxin, DNA and HCP for higher purity and increased efficiencies. 5

6 Applications for Cell Culture and Harvest and Clarification The 3M Emphaze AEX Hybrid Purifier, when used in clarification as a matched component solution with 3M s Zeta Plus depth filtration and LifeASSURE sterilising-grade membrane, enables significant process-wide improvements providing opportunity to optimise a centrifuge free process. 3% HCP and greater than 4 log DNA reduction. Consistent output turbidity (< 5 NTU). Tight particle size cut-off (< 3 nm). Greater than 6 log bioburden reduction. Cell Culture Master Cell Bank (MCB) 3M Emphaze AEX Hybrid Purifier when used as a matched component solution with a Zeta Plus filter and LifeASSURE membrane may provide a centrifuge-free direct harvest clarification using a 3-stage clarification train having sterile effluent. The 3M Emphaze AEX Hybrid Purifier s built-in.2 micron membrane provides opportunity for reduction of the sterilisation-grade membrane surface area and enables the use of.1 micron membrane. X Zeta Plus Encapsulated System Protects and improves performance of capture chromatography 3M Emphaze AEX Purifier Outstanding turbidity reduction DNA, HCP reduction Bioburden reduction LifeASSURE PDA2 (.2 μm) LifeASSURE PDA1 (.1 μm) Series Sterile Capsule Harvest and Clarification 6

7 3M Emphaze AEX Hybrid Purifi er Increased product purity post Protein A Reduction of column exposure to diffi cult-to-clean contaminants Less denaturing column cleaning Reduced column capacity fade Capture and Polish Purifi cation at the clarifi cation stage signifi cantly impacts processes downstream of the affi nity column Improvement: >1 Log HCP, >3 Log DNA Enables adoption of membrane adsorber technology in place of column chromatography Cation Exchange LifeASSURE PDA1 Series Sterile Capsule Anion Exchange Total >3 log HCP reduction >6 log DNA reduction Fill and Finish LifeASSURE PDA2 (.2 μm) LifeASSURE PDA1 (.1 μm) Series Sterile Capsule Reduction in AEX column size Lower capital expense Lower operating expense Enables membrane adsorber technology Applications for Capture and Polish, Fill and Finish 3M Emphaze AEX Hybrid Purifier performance allows reduction in the size of polishing columns which are designed to eliminate residual soluble impurities such as DNA, HCP and virus. By significantly reducing the loading of soluble impurities, such as DNA and HCP onto the capture chromatography column, 3M Emphaze AEX Hybrid Purifier substantially enhances the overall manufacturing process. DNA Reduction > 4 LRV HCP Reduction 2-4% Bioburden Reduction > 6 LRV* of Brevundimonas Diminuta Turbidity Reduction < 5 NTU Enhanced Performance of Protein A Column Protection and Cleanability Excellent mab Recovery > 95% mab * (LRV) Log Reduction Value 7

8 Process Features Superior Turbidity Reduction The 3M Emphaze AEX Hybrid Purifier provides better turbidity reduction than conventional clarification unit operations, with outlet turbidity typically < 5 NTU throughout the entirety of the clarification run, due to the combination of high anion exchange capacity and.2 μm rated membrane. Graph 1: Pressure and turbidity reduction, as a function of throughput, during clarification of a CHO centrate Outlet Turbidity (NTU) Pressure (bar) DNA Reduction Conventional Clarification 3M Emphaze AEX Hybrid Purifier 1.72 bar Pool 4.19 NTU Pool 2.19 NTU 7.53 NTU 3.39 NTU Throughput (l/m²) The 3M Emphaze AEX Hybrid Purifier has a binding capacity for DNA substantially higher than conventional depth filters. It generally provides greater than a 4 Log Reduction Value (LRV) of DNA from harvest and centrate fluids. Graph 2: Pressure and DNA reduction, as a function of throughput, during clarification of a CHO centrate DNA Reduction (LRV) Conventional Clarification 3M Emphaze AEX Hybrid Purifier Pool 4.6 LRV Pool 1.4 LRV Host Cell Protein Reduction The Q-functional nature of the 3M Emphaze AEX Hybrid Purifier provides superior reduction of negatively charged HCP. HCP reduction of 2-4% is often achieved with harvest and centrate fluids. Graph 3: Pressure and HCP reduction, as a function of throughput, during clarification of a CHO centrate HCP Reduction Pressure (bar) Bioburden Reduction The unique hybrid design of the 3M Emphaze AEX Hybrid Purifier, incorporating a.2 μm membrane, provides greater than a 6 LRV of bioburden and affords high protection of downstream sterilising membranes, including LifeASSURE.1 μm sterilising membranes for mycoplasma reduction. This enables economical strategies to reduce the risk of downstream contamination by bacteria and mycoplasma. Table 1: Results of two B. diminuta Challenges Test No. Volume, L Challenge Solution Concentration, CFU/mL Total Challenge, CFU Challenge Level, CFU/cm² Total Effluent, CFU LRV x x x x % 4% 3% 2% 1% % Conventional Clarification 3M Emphaze AEX Hybrid Purifier 1.72 bar Pool 6% reduction Pool 31% reduction Throughput (l/m²) x x x x x x x x x x x x Pressure (bar) bar Throughput (l/m²) Challenge 1 = Saline-diluted master culture, 2 L (ASTM F838-5) Challenge 2 = Undiluted master culture, 6 L 8

9 3M Emphaze AEX Hybrid Purifi er Monoclonal Antibody Process Benefits Excellent Throughput and mab Recovery While providing superior reduction of impurities including turbidity, DNA, HCP and bioburden, the 3M Emphaze AEX Hybrid Purifier generally exhibits throughput performance similar to the best commercially available fine conventional depth filters (see graphs 1-3). Also, the cationic nature of the Q-functional nonwoven and very low nonspecific binding of the all-synthetic hybrid media provide excellent mab recovery, typically exceeding the very good mab recovery achieved by conventional depth filters. Enhanced Capture Column Performance By significantly reducing the loading of soluble impurities, such as DNA and HCP, onto the capture chromatography column, the 3M Emphaze AEX Hybrid Purifier can substantially enhance its purification performance. That is, HCP and DNA reduction by the capture chromatography column may be significantly improved when the Emphaze AEX Hybrid Purifier is used for upstream clarification process. Enhanced Capture Column Protection The 3M Emphaze AEX Hybrid Purifier provides high protection of the valuable capture chromatography column, resulting in measurably fewer column-bound impurities. This has the potential to increase capture column life through less aggressive column cleaning procedures. Figure 1: HCP concentrations in CHO harvest or centrate (1), clarified fluid (2), protein A eluate (3) and clean-in-place fluid (4) when CHO harvest/centrate was clarified using either conventional clarification (blue) or Emphaze AEX Hybrid Purifier (orange). Harvest/ Clarified Protein A CIP Centrate Clarification Protein A 4M Guanidine HCI Fluid Chromatography Eluate Clean-In-Place Fluid ppm HCP/IgG % reduction 34% reduction Set-up 1, Conventional Clarification Set-up 1, 3M Emphaze AEX Hybrid Purifier Set-up 2, Conventional Clarification Set-up 2, 3M Emphaze AEX Hybrid Purifier X 19X Harvest/Centrate Clarified Fluid Protein A Eluate CIP Fluid Figure 2: DNA concentrations in CHO centrate (1), clarified fluid (2), protein A eluate (3) and acid regeneration fluid (4) when CHO centrate was clarified using either a conventional depth filter (blue) or Emphaze AEX Hybrid Purifier (orange). Clarified Protein A Regen. Protein A- Centrate Clarification Fluid Chromatography Eluate Acid Regeneration Fluid DNA Concentration (pg/ml) E E E log X 3.5 log 39 78X 3 58 Centrate Clarified Fluid Protein A Eluate Regen. Fluid X Conventional Clarification 3M Emphaze AEX Hybrid Purifier 2.7 log Advancing the Industry 9

10 Scientific Applications Support Services (SASS) 3M has a global team of market-focused scientists and engineers who excel in supporting, collaborative efforts between our customers and 3M. Our technical team is skilled in performing onsite bench-scale tests and relating the results to full-scale manufacturing process operations. When unique processing problems are encountered, our expert product and application specialists are equipped to identify solutions using 3M s broad array of existing products and solutions. Scientific Services Post-use Integrity Test Process Fluid Correlation Bacterial Challenge Test ASTM - Brevundimonas Dimunuta ATCC Acholoeplasma laidlawii ATCC 2326 Compatibility Sterilisation Solvents Integrity Viability Adsorption Binding - Equilibrium - Recovery Extractables and Leachables Flush-up Studies Recirculation Studies United States Pharmacopoeial (USP) - Microbiological Tests (61, 62, 63, 71) - Biological Tests (85, 87, 88) - Chemical Tests (231, 233, others as required) - Physical Tests (631, 643, 645, 661, 787, 788, 79, 791) GMP Guidelines Flushing St. Paul, MN, USA Antwerp, Belgium Tokyo, Japan Sumaré, Brazil Shanghai, China Cairo, Egypt Bangalore, India 3M Purification provides comprehensive technical services and advanced engineering support for biopharmaceutical customers from centres around the world. 3M Validation Laboratory 3M Technical Specialist 3M Corporate Research Laboratory Global Support Network 1

11 3M Emphaze AEX Hybrid Purifi er Product Selection/Specification Product Name BV8 BV6 BV12 BV36 BV8 BV56 Model Number EMP31AEX2A EMP33AEX2A EMP53AEX2A EMP513AEX2A EMP533AEX2A EMP71AEX2A EMP77AEX2A Part Number Global Part Number Height x Diameter 4.5 cm x 7.7 cm 8.8 cm x 7.7 cm 1.3 cm x 21.6 cm 15.2 cm x 21.6 cm 5.7 cm x 45.2 cm 2.3 cm x 45.2 cm Weight Dry 71 g 77 g 1. kg 1. kg 1.4 kg 3.1 kg 9.2 kg Weight Wet Post Blow Down 8 g 85 g 1.1 kg 1.1 kg 1.9 kg 3.8 kg 13.9 kg Fill Volume 1 13 ml 16 ml 55 ml 55 ml 1.4 l 3.4 l 1.6 l Hold Up Volume Post Blow Down 2 9 ml 1 ml 15 ml 46 ml 7 ml 47 ml Capsule Material Polypropylene, Glass-fi lled Polypropylene Polysulfone, Polypropylene, Thermoplastic Elastomer, Fluorocarbon Polycarbonate, Polypropylene, Thermoplastic Elastomer, Silicone.9 l 5.5 l 12 l 85 l Sterilisation Post Use Post use 1 autoclave cycle at 121 ºC for 3 minutes Post use 1 autoclave cycle at 126 ºC for 3 minutes Inlet/Outlet Connections Luer Fitting ½ or ¾ Sanitary Connector 1 ½ Sanitary Connector (manifold) Max. Inlet Pressure bar 3.1 bar 3.4 bar Max. Differential Pressure 2.4 bar Max. Temperature 4 ºC Required Preconditioning.13 l 1.8 l Flush Volume 4 Recommended Use Flow Rate 8 ml/min 5 ml/min 1 ml/min 3 ml/min 7 ml/min 49 ml/min Storage Conditions Controlled Indoor Temperatures: - 3 C in original sealed packaging Shelf-life 5 Up to 2 years from date of manufacture at maximum 3 C Do not sterilise or sanitise pre-use 1 Capsule Fill Volume is defi ned as the volume of liquid that is required to fi ll the capsule. 2 Post Blow Down Hold Up Volume is defi ned as the volume of the residual liquid after air/gas blow down. 3 Do not use this product for continuous service with compressed gasses. The use of compressed gas is permissible for integrity testing and blow down purposes. 4 The Preconditioning Flush is required for the product to be compliant with USP Biological Reactivity Tests including USP36 <87> and <88> Class VI. The fl ush solution can be a buffer or mm sodium chloride solution. 5 3M Emphaze AEX Hybrid Purifi ers are designed to maintain USP <88> Class VI compliance and high adsorption capacity for up to 2 years from date of manufacture. Product labeling includes the expiration date. A full support package is available for 3M Emphaze AEX Hybrid Purifiers. This package includes Installation and Operation Guides, Certificate of Quality and a Regulatory Support File. Hardware and Single-Use Manifold Ordering Information Model Name Description Part Number Global Part Number 1EZA Stainless Steel Holder 1 BV56 capsule EZA Stainless Steel Holder up to 3 BV56 capsules EZB Stainless Steel Holder up to 7 BV56 capsules Manifold Set Top and Bottom Manifold for use with BV8 and BV56 Please contact your local representative for further information

12 3M Emphaze AEX Hybrid Purifi er Product Scaling Configurations CAPACITY x7 or x14 Lab/ R&D.5-1 L x3 or x6 Scale-Up 1-5 L 5-25 L x2.3 to x15.6 Pilot Production 25-2 L x7 to x49 Scale-Up Factors x >2 Large Scale Production L Production Scale Products Multi-Round Production 2-25 L PROCESS VOLUME Important Notice The information described in this literature is accurate to the best of our knowledge. A variety of factors, however, can affect the performance of the Product(s) in a particular application, some of which are uniquely within your knowledge and control. INFORMATION IS SUPPLIED UPON THE CONDITION THAT THE PERSONS RECEIVING THE SAME WILL MAKE THEIR OWN DETERMINATION AS TO ITS SUITABILITY FOR THEIR USE. IN NO EVENT WILL 3M PURIFICATION BE RESPONSIBLE FOR DAMAGES OF ANY NATURE WHATSOEVER RESULTING FROM THE USE OF OR RELIANCE UPON INFORMATION. It is your responsibility to determine if additional testing or information is required and if this product is fi t for a particular purpose and suitable in your specifi c application. 3M PURIFICATION MAKES NO REPRESENTATIONS OR WARRANTIES, EITHER EXPRESS OR IMPLIED INCLUDING WITHOUT LIMITATION ANY WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE OR OF ANY OTHER NATURE HEREUNDER WITH RESPECT TO INFORMATION OR THE PRODUCT TO WHICH INFORMATION REFERS. Limitation of Liability 3M Purifi cation will not be liable for any loss or damage arising from the use of the Product(s), whether direct, indirect, special, incidental, or consequential, regardless of the legal theory asserted, including warranty, contract, negligence or strict liability. Some states do not allow the exclusion or limitation of incidental or consequential damages, so the above limitation may not apply to you. 3M Belgium BVBA/SPRL - 3M Purification 3MPurifi cation.be@mmm.com Address details: 3M Nederland BV - 3M Purification 3MPurifi cation.nl@mmm.com Address details: 3M, Emphaze, Zeta Plus and LifeASSURE are registered trademarks of the 3M Company. All other trademarks are the property of their respective owners. For more products and product applications visit our website at cation or cation. Data may be subject to change without further notice. 3M 215. All rights reserved. v.2 - DOC1357 LITCTEMP1.EU - 115