3M InnovationTransform & Redefine

Efficiency. Purity. Economics.

3M™ Emphaze™ AEX Hybrid Purifi erSingle-Use Clarifi cation and Purifi cation for Biopharmaceutical Processes

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.

Transforming

Ideasinto Realities.t

3M Innovation: Making Progress Possible3M creates transformational products and solutions that enable customer successes and improve people’s lives around the world.

We utilize 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 50 diverse technology platforms

• Fostering a culture of intellectual curiosity and creativity the pushes boundaries

3M Advancing the Biopharmaceutical IndustryAt 3M, we are advancing the global pharmaceutical industry by helping to build products that enable better and more effi cient manufacturing processes. The Life Sciences Process Technologies business unit of 3M Purifi cation Inc. provides cutting edge technologies to address fi ltration and purifi cation needs of the global biopharmaceutical industry. We deliver novel products to enable reduction in the complexity and cost of pharmaceutical production processes.

2

“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.

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FeFlexibleElectronics

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LmLight Management

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MeMetal Matrix Composites

MfMechanical Fasteners

MiMicrobial Detection & Control

MoMolding

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PePredictiveEngineering & Modeling

PmPolymer Melt Processing

PpPrecision Processing

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SeSensors

TtTrack & Trace

VpVapor Processing

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WoWound Management

NwNonwoven Materials

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PdParticle & Dispersion Processing

NtNano-technology

PoPorous Materials & Membranes

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Unique 3M Technology The 3M™ Emphaze™ AEX Hybrid Purifi er is created using the unique combination of numerous 3M prioprietary 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 Purifi er combines: advanced polymer materials, a novel anion exchange hydrogel nonwoven media integrated with a fi ne particle, bioburden reduction multi-zone membrane.

3

Transforming the Biopharmaceutical Production Process: Effi ciency. Purity. Economics.

The 3M™ Emphaze™ AEX Hybrid Purifi er represents a new class of clarifying products that can be applied to redefi ne your manufacturing processes for the production of therapeutic proteins like monoclonal antibodies (mAb), blood proteins and vaccines.

3M Emphaze AEX Hybrid Purifi er, the fi rst in a series of chromatography and membrane chromatographic products, designed to remove insoluble and soluble impurities, like cell debris, aggregates, bacteria, DNA, HCP, & virus, which helps optimize downstream processes. Through a unique combination of 3M technologies, 3M has created an encapsulated, single-use all-synthetic clarifying media based on a hyperfunctionalized nonwoven media.

The 3M Emphaze AEX Hybrid Purifi er delivers clarifi ed process fl uid by removing insoluble impurities, such as cell debris, aggregates and bacteria, through a combination of chromatographic and size exclusion mechanisms.

When used at the clarifi cation stage, the Matched Component combination of 3M Emphaze AEX Hybrid Purifi er, Zeta Plus™ depth fi lters and LifeASSURE™ membrane fi lters provide a process with increased effi ciency and protein purity. This can enable the reduction of substantial biopharmaceutical manufacturing costs.

Making Your Job EasierIncreased Process Effi ciencies • 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 Purifi er and LifeASSURE™ Membrane Filters can eliminate the need for the centrifuge unit operation and also reduce the required area of the downstream sterilizing 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 purifi cation performance.

Simplifi ed Manufacturing Process • Elimination or optimization of unit operations results

in signifi cant manufacturing operational effi ciency improvement.

Signifi cant biopharmaceutical process-wide improvements are achieved when deployed at the clarifi cation stage of the monoclonal antibody purifi cation:

High performance clarifi cation

• Nominal 30% HCP and greater than 4 log DNA reduction • Consistent output turbidity (< 5 NTU)• Tight particle size cut-off (<30 nm)• Greater than 6 log bioburden reduction

Enables higher Protein A column performance

• > 10x less HCP in the product stream post Protein A • > 1000x reduction in DNA concentration post Protein A • > 10x less residual contaminants on Protein A column• Reduced column capacity fade and potentially extended

column life

Enables tighter sterilizing fi lters w/less surface area

• Seamless 0.2 μm to 0.1 μm transition • Signifi cant reduction in fi lter surface area

Enables smaller downstream AEX column

• > 10x less contaminants • Target protein at or near regulatory HCP and DNA

contaminate purity requirements

3M™

Emphaze™

AEX Hybrid Purifi er4

4 layers of Q-functional Nonwoven Media Strong anion exchange chromatographic media, comprised of a hydrogel functionalized nonwoven, provides unsurpassed removal of insoluble and soluble impurities such as cell debris, aggregates, bacteria, DNA, HCP, and virus.

Highly Asymmetric 0.2 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.

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 0.2 or 0.1 grade micron membrane alone

• Superior turbidity (particle) removal: <5 NTU • >6 log bioburden reduction • Even fl ow distribution

Anion ExchangeSignifi cant 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 effi ciencies.

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Zone 1-3

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Layer 2

Layer 3

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Unique Product. Unique Construction.The 3M™ Emphaze™ AEX Hybrid Purifi er is an integral combination of two types of purifi cation media that work together to provide unsurpassed product purity in a single unit operation.

The all-synthetic purifi cation media and unique layering construction provides unsurpassed purity by integrating multiple separation mechanisms into one single-use product:

5

Master Cell Bank(MCB)

Zeta Plus™ Encapsulated System • Protects and improves

performance of capture chromatography

3M™ Emphaze™ AEX Hybrid Purifier • Outstanding turbidity reduction • DNA, HCP reduction • Bioburden reduction

LifeASSURE™ PDA010Series Sterile Capsule • 0.1μm sterilizing membrane

• Bacteria and mycoplasma removal

The 3M Emphaze AEX Hybrid Purifi-er’s built-in 0.2 micron membrane provides opportunity for reduction of the sterilization grade membrane surface area and enables the use of 0.1 micron membrane.

• 3M™ Emphaze™ AEX Hybrid Purifier when used as a Matched Component Solution with a Zeta Plus filter and LifeASSURE membrane provides a centrifuge-free direct harvest clarification using a 3-stage clarification train having sterile effluent. XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

The 3M™ Emphaze™ AEX Hybrid Purifi er, when used in clarifi cation as a Matched Component Solution with 3M’s Zeta Plus™ depth fi ltration and LifeASSURE™ sterilizing grade membrane, enables signifi cant process-wide improvements providing opportunity to optimize a centrifuge free process.

• 30% HCP and greater than 4 log DNA reduction • Consistent output turbidity (< 5 NTU) • Tight particle size cut-off (<30 nm) • Greater than 6 log bioburden reduction

Cell Culture

Harvest & Clarifi cation

Applications for Cell Culture and Harvest & Clarifi cation

6

3M™ Emphaze™ AEX Hybrid Purifi er performance allows reduction in the size of polishing columns which are designed to eliminate residual soluble impurities such as DNA, HCP, and virus. By signifi cantly reducing the loading of soluble impurities, such as DNA and HCP onto the capture chromatography column, 3M Emphaze AEX Hybrid Purifi er substantially enhances the overall manufacturing process.

LifeASSURE™ PDA010Series Sterile Capsule

• Purification at the clarification stage signifi-cantly impacts processes downstream of the affinity column

- Improvement: >1 Log HCP, >3 Log DNA • Enables adoption of membrane adsorber

technology in place of column chromatography

LifeASSURE™ PDA020 (0.2µm)LifeASSURE™ PDA010 (0.1µm)Series Sterile Capsule

Total>3 log HCP reduction>6 log DNA reduction

Anion Exchange

Cation Exchange

• Reduction in AEX column size • Lower capital expense • Lower operating expense • Enables membrane

adsorber technology

• Increased product purity post Protein A • Reduction of column exposure to

difficult-to-clean contaminants - Less denaturing column cleaning - Reduced column capacity fade

Capture & Polish

Fill & Finish

Applications for Capture & Polish,Fill & Finish

7

Process Features Superior Turbidity ReductionThe 3M™ Emphaze™ AEX Hybrid Purifi er provides better turbidity reduction than conventional clarifi cation unit operations, with outlet turbidity typically < 5 NTU throughout the entirety of the clarifi cation run, due to the combination of high anion exchange capacity and 0.2 μm rated membrane.

Graph 1: Pressure and turbidity reduction, as a function of throughput, during clarifi cation of a CHO centrate

DNA ReductionThe 3M Emphaze AEX Hybrid Purifi er has a binding capacity for DNA substantially higher than conventional depth fi lters. It generally provides greater than a 4 Log Reduction Value (LRV) of DNA from harvest and centrate fl uids.

Graph 2: Pressure and DNA reduction, as a function of throughput, during clarifi cation of a CHO centrate

Host Cell Protein ReductionThe Q-functional nature of the 3M Emphaze AEX Hybrid Purifi er provides superior reduction of negatively charged HCP. HCP reduction of 20-40% is often achieved with harvest and centrate fl uids.

Graph 3: Pressure and HCP reduction, as a function of throughput, during clarifi cation of a CHO centrate

Bioburden ReductionThe unique hybrid design of the 3M Emphaze AEX Hybrid Purifi er, incorporating a 0.2 μm membrane, provides greater than a 6 LRV of bioburden and affords unsurpassed protection of downstream sterilizing membranes, including LifeASSURE™ 0.1 μm sterilizing 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 Concen-tration, CFU/mL

Total Challenge,

CFU

Challenge Level,

CFU/cm2

Total Effl uent,

CFULRV

1 0-2 6.8 x 106 1.4 x 1010 8.2 x 107 1.0 x 102 8.1

2

0-2 5.4 x 106 1.1 x 1012 6.5 x 109 1.3 x 105 6.9

2-4 5.4 x 106 2.2 x 1012 1.3 x 1010 4.3 x 105 6.7

4-6 5.4 x 106 3.2 x 1012 1.9 x 1010 1.1 x 106 6.5

Challenge 1 = Saline-diluted master culture, 2 L (ASTM F838-05)

Challenge 2 = Undiluted master culture, 6 L

7.53 NTU

3.39 NTU

Conventional Clarification

3M™ Emphaze™ AEX Hybrid Purifier

8

7

6

5

4

3

2

1

0

20

10

0

Outle

t Tur

bidi

ty, N

TUPr

essu

re, p

si

Throughput, L/m20 100 200 300 400 500 600 700 800

Pool4.19 NTU

Pool2.19 NTU25 psi

Conventional Clarification

3M™ Emphaze™ AEX Hybrid Purifier

6

5

4

3

2

1

0

20

10

0

DNA

Redu

ctio

n, L

RVPr

essu

re, p

si

Throughput, L/m20 100 200 300 400 500 600 700 800

25 psi

Pool1.4 LRV

Pool4.6 LRV

Conventional Clarification

3M™ Emphaze™ AEX Hybrid Purifier50%

40%

30%

20%

10%

0%

20

10

0

HCP

Redu

ctio

nPr

essu

re, p

si

Throughput, L/m20 100 200 300 400 500 600 700 800

25 psi

Pool6% Reduction

Pool31% Reduction

8

Redefi ning the

processes for the

production of therapeutic proteins

9

Graph 5: DNA concentrations in CHO centrate (1), clarifi ed fl uid (2), protein A eluate (3), and acid regeneration fl uid (4) when CHO centrate was clarifi ed using either a conventional depth fi lter (blue) or 3M™Emphaze™ AEX Hybrid Purifi er (orange).

Graph 4: HCP concentrations in CHO harvest or centrate (1), clarifi ed fl uid (2), protein A eluate (3), and clean-in-place fl uid (4) when CHO harvest/centrate was clarifi ed using either conventional clarifi cation (blue) or 3M™ Emphaze™ AEX Hybrid Purifi er (orange).

19X

78X

17X

Harvest/ Centrate

Clarified FluidClarification Protein A

ChromatographyProtein A

Eluate4M Guanidine HCl

Clean-In-PlaceCIP

Fluid

Centrate Clarified FluidClarification Protein A

ChromatographyProtein A

Eluate Acid RegenerationRegen. Fluid

4.0 log

3.5 log

2.7 log

Advancing the Industry

Monoclonal Antibody Process Benefi tsExcellent Throughput and mAb RecoveryWhile providing superior reduction of impurities including turbidity, DNA, HCP, and bioburden, the 3M™ Emphaze™ AEX Hybrid Purifi er generally exhibits throughput performance similar to the best commercially available fi ne conventional depth fi lters (see Graphs 1-3). Also, the cationic nature of the Q-functional nonwoven and very low nonspecifi c binding of the all-synthetic hybrid media provide excellent mAb recovery, typically exceeding the very good mAb recovery achieved by conventional depth fi lters.

Enhanced Capture Column PerformanceBy signifi cantly reducing the loading of soluble impurities, such as DNA and HCP, onto the capture chromatography column, Emphaze AEX Hybrid Purifi er can substantially enhance its purifi cation performance. That is, HCP and DNA reduction by the capture chromatography column may be signifi cantly improved when Emphaze AEX Hybrid Purifi er is used for upstream clarifi cation process.

Enhanced Capture Column ProtectionThe 3M Emphaze AEX Hybrid Purifi er provides unsurpassed 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.

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3M Validation Laboratory3M Technical Specialist3M Corporate Research Laboratory

St. Paul, MN, USA

Antwerp, Belgium

Tokyo, Japan

Cairo, Egypt

Shanghai, China

Bangalore, India

Sumaré, Brazil

3M Purifi cation provides comprehensive technical services and advanced engineering support for biopharmaceutical customers from centers around the world.

GlobalSupport

NetworkScientifi c 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 on-site 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.

Scientifi c ServicesPost-use Integrity Test

• Process Fluid • Correlation

Bacterial Challenge Test • ASTM

- Brevundimonas Dimunuta

ATCC 19146

- Acholoeplasma laidlawii ATCC 23206

Compatibility • Sterilization • Solvents • Integrity • Viability

Adsorption • Binding

- Equilibrium

- Recovery

Extractables and Leachables • Flush-up Studies • Recirculation Studies • United State 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, 790, 791)

• GMP Guidelines • Flushing

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Please recycle. Printed in U.S.A.3M, LifeASSURE and Emphaze are trademarks of 3M Company.All other trademarks are the property of their respective owners© 2014 3M Company. All rights reserved.70020323997 REV 1214

3M Purifi cation Inc.400 Research ParkwayMeriden, CT 06450U.S.A.Phone (800) 243-6894 (203) 237-5541Fax (203) 630-4530www.3Mpurifi cation.com/Emphaze

Product Selection/Specifi cationProduct Name BV8 BV60 BV120 BV360 BV800 BV5600Model Number EMP301AEX020A EMP303AEX020A EMP503AEX020A EMP513AEX020A EMP533AEX020A EMP710AEX020A EMP770AEX020A

Part Number 70020330570 70020330588 70020301662 70020301670 70020301688 70020301696 70020301704

Global Part Number 7100053362 7100053364 7100029619 7100029617 7100029616 7100048383 7100048384

Height x Diameter4.5 cm x 7.7 cm

(1.7" x 3.0")

8.8 cm x 7.7 cm

(3.5" x 3.0")

10.3 cm x 21.6 cm

(4.1" x 6.5")

15.2 cm x 21.6 cm

(6.0" x 6.5")

5.7 cm x 45.2 cm

(2.2" x 17.8")

20.3 cm x 45.2 cm

(8.0" x 17.8")

Weight Dry 71 g 77 g 1.0 kg 1.0 kg 1.4 kg 3.1 kg 9.2 kg

Weight Wet Post Blow Down

80 g 85 g 1.1 kg 1.1 kg 1.9 kg 3.8 kg 13.9 kg

Fill Volume1 13 mL 16 mL 550 mL 550 mL 1.4 L 3.4 L 10.6 L

Hold Up Volume Post Blow Down2 9 mL 100 mL 150 mL 460 mL 700 mL 4700 mL

Capsule MaterialPolypropylene,

Glass-fi lled Polypropylene

Polysulfone, Polypropylene, Thermoplastic Elastomer,

Fluorocarbon

Polycarbonate, Polypropylene,

Thermoplastic Elastomer, Silicone

Sterilization Post Use Post use 1 autoclave cycle at 121 ºC for 30 minutes Post use 1 autoclave cycle at 126 ºC for 30 minutes

Alkaline Resistance Post Use

Capsule compatibility based on testing with 1M NaOH and 5% NaClO (bleach)Capsule compatibility based on testing

with 5% NaClO (bleach)

Inlet/Outlet Connections Luer 1/2” or 3/4” Sanitary Style 1.5” Sanitary Style (manifold)

Max. Inlet Pressure3 2.8 bar (40 psig) 3.1 bar (45 psig) 3.4 bar (50 psig)

Max. Differential Pressure 2.4 bar (35 psid)

Max. Temperature 40 ºC (104 ºF)

Required Precondition-ing Flush Volume4 0.13 L 0.9 L 1.8 L 5.5 L 12 L 85 L

Recommended UseFlow Rate

8 mL/min 50 mL/min 100 mL/min 300 mL/min 700 mL/min 4900 mL/min

Storage Conditions Controlled Indoor Temperatures: 0 - 30 °C (32 - 86 °F) in original sealed packaging

Shelf-Life5 2 years from data of manufacture @ 30°C maximum storage

Do not sterilize or sanitize pre-use1 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 USP<87> and <88> Class VI. The fl ush solution can be a buffer or 25-150 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 Purifi ers.This package includes Installation and Operation Guides, Certifi cate of Quality, and a Regulatory Support File.

Other Recommended ApplicationsThe 3M Emphaze AEX Hybrid Purifi er is designed to remove insoluble and soluble particles and impurities such as cell debris, aggregates, bacteria, virus, endotoxin, DNA and HCP from the biopharmaceutical manufacturing process. Other applications include: Vaccine production & Blood fractionalization.

Warranty and Limited Remedy: 3M warrants that each 3M product meets the applicable 3M product specifi cation at the time 3M ships the product. 3M MAKES NO OTHER EXPRESS OR IMPLIED WARRANTIES OR CONDITIONS, INCLUDING ANY IMPLIED WARRANTY OR CONDITION OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. If the 3M product does not conform to this warranty, the sole and exclusive remedy is, at 3M’s option, replacement of the 3M product or refund of the purchase price. Limitation of Liability: Except where prohibited by law, 3M will not be liable for any loss or damage arising from the 3M product, whether direct, indirect, special, incidental or consequential, regardless of the legal theory asserted.

For more information about the 3M Emphaze platform or our 3M Validation Services designed to support your adoption of this new product line, please contact your local Life Sciences territory Sales Manager, call 1-800-243-6894, Option 4 or visit our website at www.3Mpurifi cation.com/Emphaze.