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© YMC Process Technologies Group
Multi-column chromatography
Built on patented & licensed technology from
Increasing productivity and decreasing costs in the downstream process
Who we are
Products
Focus on EcoPrime Twin LPLC
Case Studies
YPT Manufacturing CampusLocation 60 kms from Boston, MA USA in “biotech corridor”
© LEWA 3
YPT shop has over 22,000 square feet of (2,050 m2) manufacturing space with 37-foot (11 m) bay ceilings
Part of YPT Process Production Facility
4
GMP Skid Manufacturing Area
11/7/2018 5
11/7/2018
5
6 sales support and mktg 20 engineering and quality 20 operations staff 3 general and administrative
Devens, MA USA2000
100% subsidiary of YMC Co., Ltd.
Quality: ISO 9001:2015 Registration Planned for 2019
Supply chain – Prep SystemsBio pharmaceuticalPharmaceuticalOEM (bio/pharma)
GMP scale systems engineering, manufacturing & automation;• Chromatography• Buffer In-line Dilution• Downstream process skids
COO – Mark DymentCMO – Gerard GachCSO – Wayne Nettnay
YMC Process Technologies Group
Employees: ~50 Total
LocationDate of Establishment
Ownership
Quality System
Business Status
Target markets
Core business
Exec staff
Video Link Here
YMC Process Technologies Bio/Pharma Systems’ Group –Factsheet
FAT Area
6
Product Characterization & Demo Laboratory
YPT has dedicated
space to characterize &
demonstrate our
products for the
customers.
Also “overflow” space
for FAT.
7
Work Flow For YPT- design, automate, manufacture
YPT maintains a full compliment of departments that ensure the project has the right resources
Vertical Supply – Controls quality from beginning to end of your project
– Complete array of expertise
to ensure comprehensive
management of the design
– Process experts at each step.
Process Engineering
Mechanical/Design/CAD Engineering
Automation Engineering
Manufacturing / Fabrication
1
2
3
Project Mangement
QA/QC
Constant Customer Interface
4
Subject Matter Experts
LPT/YPT history
2010
Collaboration
2015Acquisition
2000
Established
2020Integration
2018
The Products
Capture 2 column LPLC
A sampling of bioprocess systems we have produced
MCSGP 2 column LPLC & HPLC
Simulated Moving Bed HPLC
12Configurable to fit customer needs - ~ 20 options to select from
EcoPrime LPLC Select Features
13
Using concentrated buffers the EcoPrime
buffer in-line dilution (BID) option will:
- significantly reducing tank footprint
- freeing up plant space
- lowering your operation expenses.
Chromatography and buffer in-line dilution
are integrated on the same system
combining two unit operations into a single
platform!
Integrated buffer in-line dilution (BID) =Lower capex and opex – two units in one
We partner with ChromaCon AG using their IP for twin-column processes.
© YMC 14
YPT manufactures pilot & production scale multi-column chromatography systems
Seamless scale-up
CaptureSMB
MCSGP
ChromaCon•Process know-how• Intellectual property•Entry-stage equipment
YMC• Scale-up Equipment• Process solutions• Columns / resins• Continuous manufacturing• Worldwide Footprint
Video Link Here
Benefits of YMC EcoPrime® Twin LPLC
© YMC Group and 15
Huge productivity10 cm ID Protein A columns –
more than 1 kg mAb purified/day (500 L feed)
SimplicityTwo column design minimizes
complexity and secures maximum uptime
Easy scale upProcess design on the
Contichrom CUBE, fast scale-up to EcoPrime Twin The 2-column approach reduces
risk • Accelerates validation• Simplifies maintenance• Lessens costly downtime• Minimizes hold-up and operating expenses• Streamlines implementation; easy-to-
understand and use
Award Winner!
© LEWA - Bioprocess Group 16
https://aspenxchange.com/aspen-award
Advancement of Downstream Bioprocessing
- 2017 -LEWA Bioprocess Group
EcoPrime Twin LPLC
The most innovative new products that have
made the greatest contribution to the advancement of bioprocessing.
Proven scale to GMP
© LEWA GmbH, LEWA Imagepresentation, v1.1 17
30 mL/min
20,000 mL/min
600 mL/min
Multi-function systems - not just multi-column capture.
11/7/2018© YMC Process Technologies. 18
Twin Column CaptureSMB
Base EcoPrime Twin includes patented multi-column functionality
Multi-function systems – conventional batch
© YMC Process Technologies. 19
Twin Column CaptureSMB
CEXAEX
Batchsingle or “flip-flop” column
chromatography
Multi-function systems – Sequential process functionality available
11/7/2018© YMC Process Technologies. 20
Twin Column CaptureSMB
Sequential polish
chromatography
CEXAEX
Batchsingle or “flip-flop”
column chromatography
Multi-function systems – buffer from concentrates
© YMC Process Technologies. 21
Twin Column CaptureSMB
Sequential polish chromatography
CEXAEX
Batchsingle or “flip-flop” column
chromatography
Buffer In-line
Dilution
Multi-function systems - not just continuous capture
© YMC Process Technology
22
Twin Column CaptureSMB
Sequential polish
chromatography
CEXAEX
Batchsingle or “flip-flop” column
chromatography
Buffer In-line
Dilution
Risk reduction, process intensification, reduce footprint and manufacturing flexibility
© YMC Process Technologies.23
Novel engineering maintains aseptic pathway from single use buffer and feed to system
We have optimized to link directly to a single use environment – while maintaining an aseptic flow path
Option available at additional cost on base system
Aseptic connectors sanitized by gamma on one side and NaOH on system side.
Allows closed environment maintained between runs.
System can be operated in lower classification suite.
© YMC Process Technologies.24
Automation flexibility
© YMC Process Technologies.
25
Newest version PAC
• ControlLogix• FactoryTalk
DELTAV
direct control by DeltaV based
program supplied by LEWA
Customer can elect either control platform
Base
Sys
tem
Pr
opos
al
Opt
ion
avai
labl
e at
add
ition
al c
ost
on b
ase
syst
em
Simple and robust design
26
The 2-column approach reduces risk • Accelerates validation• Simplifies maintenance• Lessens costly downtime• Minimizes hold-up and operating expenses• Streamlines implementation; easy-to-
understand and use
8 column process~240 Valves < 40 Valves
CUBE from ChromaCon® LEWA EcoPrime Twin
© LEWA Bioprocess Group and
27
2 ecodos pumps
Pump B (feed)with 4 inlets
Pump A (Buffer)with 6 inlets
2 Flow meters
Column inletvalve block
Column outletvalve block
Outlet valve block
Single outlet valve
pH probe
2 UV detectors2 conductivityand temperature
Column inlets and outlets and their by-passes
EcoPrime Twin LPLC designEcoPrime Twin 100
1. Symmetric design2. Minimum hold-up volume 3. Simple piping design
Pressure Rating up to 7.5 bar (design pressure) – max. operating pressure ~6 bar.
UV-Detection: 280 and 303 nmConductivity Range: 0 – 200 mS/cmpH-Range: 2 – 12
UV signals of four cycles (column 1 and column 2)
Seamless scale-up of a continuous capture process
28
ContichromCUBE
EcoPrimeTwin
© YMC Process Technologies.
Information-rich, graphical user interface
Process flow chart with sensors to monitor and control process.
Trends,Sequences and Recipes,Reporting and Alarms …
HMI – main screen (EcoPrime Twin LPLC System)
29
User trained on day 1 and up and running on day 2
© YMC Process Technologies.
Recipe-driven process configuration
• Easily create recipes from preconfigured sequences
• ‘Development’ and ‘Production’ recipes with access control
• All data stored in a database for audit trail
30
Simple design, simple to set up & run
31
Video Link Here
Set up / run system <1 day*
© YMC Process Technologies. * EP Twin 100 model GMP scale demo system
YPT EcoPrime Twin 100 LPLC
0
50
100
150
200
250
300
350
Feed
pum
p (m
l/min
)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
disc
harg
e (b
ar)
Consistent and robust performance
Robust design for extended run time performance
32
Monitoring feed flow rate and pump discharge pressure (Shown - last 24 hours only)
Long-term study over 210 loads (13 days) (EcoPrime Twin 100)
© YMC Process Technologies.
Consistent & reproducible performance
Reproducibility during continuous operation on EcoPrime Twin 100
33
Conductivity monitored at the outlet of each column
© YMC Process Technologies.
Case Study CUBE + EcoPrime Twin
© YMC Process Technologies.34
Customer
User data shows >2X productivity and ~50% buffer savings.
© YMC Process Technologies. 35
Paper published in February 2018: http://www.bioprocessintl.com/
Successful 100X scale-up.Now proceeding to production scale.
© YMC Process Technologies.36
Batch captureLoad 50 g/L resinTotal CV 17.3 L
Continuous capture Load 80 g/L resinTotal CV 1.6 L
Seamless transfer from batch to continuous captureCustomer B – pilot plant process comparison; 5 g/L titer mAb
CV linear [cm/h]
Pre
‐
Sanitization 3 400Equilibration 3 400Load 4.6 100Load interconnected 11.4 150Wash 1 2 400Wash 2 5 400Wash 3 3 400Elution 3.5 400CIP 3 400Re-equilibration 3 400Sanitization 3 400Neutralization 2 3 400Storage 3 400
CV linear [cm/h]
Pre
‐
Sanitization 3 300Equilibration 3 300Load 10 150Wash 1 2 300Wash 2 5 300Wash 3 3 300Elution 5 300CIP 3 300Neutralization 1 3 300Sanitization 3 300Neutralization 2 3 300Storage 3 300
Essentially same process steps = simple process transfer
© YMC Process Technologies.37
Batch captureLoad 50 g/L resinTotal CV 17.3 L
Continuous capture Load 80 g/L resinTotal CV 1.6 L
Continuous capture has advantages Customer B – pilot plant process comparison; 5 g/L titer mAb
CV linear [cm/h]
Pre
‐
Sanitization 3 400Equilibration 3 400Load 4.6 100Load interconnected 11.4 150Wash 1 2 400Wash 2 5 400Wash 3 3 400Elution 3.5 400CIP 3 400Re-equilibration 3 400Sanitization 3 400Neutralization 2 3 400Storage 3 400
CV linear [cm/h]
Pre
‐
Sanitization 3 300Equilibration 3 300Load 10 150Wash 1 2 300Wash 2 5 300Wash 3 3 300Elution 5 300CIP 3 300Neutralization 1 3 300Sanitization 3 300Neutralization 2 3 300Storage 3 300
Higher load 10 vs 16 CVs higher resin utilization & reduce buffer consumptionFaster linear velocity shorter processing time
Process time: 4.5 h Cycle time: 2.5 h
© YMC Process Technologies.38© LEWA - Bioprocess Group
EcoPrime Twin run with 14-h process time
peak area peak area1 0.239 0.2762 0.255 0.2833 0.259 0.2854 0.260 0.286
average 0.2583 0.2849error %* 1.1 0.7
Column 1 Column 2peak #
Variability of peak area is ~1 % at
steady stateContichrom Cube run with 12-h process time
Steady state can be reached with first
elution.Similar chromatograms when scaling up and down
Reproducibility and scalabilityCustomer B – 5g/L titer mAb: 80 g/L load
39
Comparison batch to continuous captureCustomer B - process development run: 5 g/L titer mAb
> 2X productivity or 50 % less resin and ~ 50 % buffer reduction
0
5
10
15
20
25
Batch EcoPrime Twin Contichrom Cube
8.4
20.622.2
Prod
uctiv
ity [g
/Lre
sin/
h]
Productivity - Customer B
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Batch EcoPrime Twin Contichrom Cube
0.73
0.36 0.34
Buffe
r Con
sum
ptio
n [L
/g]
Buffer Consumption - Customer B
© YMC Process Technologies.
Example BMS - Downstream with EcoPrime Twin in
Capture and Polish Steps (resin/membrane)
40
Case Study #1
© YMC Process Technologies.41
Customer “A”
42
Batch Capture Total CV 7.85 L
Continuous Capture Total CV 1.6 L
Simple transfer from batch to continuous captureCustomer A - process development run comparison with 1g/L titer mAb
Essentially same process steps = simple process transfer
Linear[cm/h]
Column Equilibration 3 250Load 40 150Wash 1 2 150Wash 2 2 250Wash 3 3 250 Elution 3 250post wash 1 3 250post wash 2* 2 250Regen* 3 250
CVCV
Load Start-Up 15Load Connected 27Load Parallel 22Wash 1 connected 1Wash 1 Parallel 1Wash 2 2Wash 3 3Elution 3Post-Wash1 2Post Wash 2 1Regeneration 3Re-Equilibration 5
© YMC Process Technologies.
43
Batch Capture Total CV 7.85 L
Continuous Capture Total CV 1.6 L
Continuous capture has advantagesCustomer A - process development run comparison with 1g/L titer mAb
Higher load volume 40 vs 49 CVs higher resin utilization & reduce buffer consumptionShorter residence times faster loading & shorter processing time
Linear[cm/h]
Column Equilibration 3 250Load 40 150Wash 1 2 150Wash 2 2 250Wash 3 3 250 Elution 3 250post wash 1 3 250post wash 2* 2 250Regen* 3 250
CV
Process time: 9 hCycle time: 4 h at linear velocity of 250 cm/h
CVLoad Start-Up 15Load Connected 27Load Parallel 22Wash 1 connected 1Wash 1 Parallel 1Wash 2 2Wash 3 3Elution 3Post-Wash1 2Post Wash 2 1Regeneration 3Re-Equilibration 5
© Y
MC
Proc
ess T
echn
olog
ies. Same amount of material can
be processed in 50% less time
(CIP) (CIP) after every 4th cycle
Strong continuous capture reproducibilityCustomer A using EcoPrime Twin 100 – 1g/L titer run results at 40 g/L load
44
7 peaks overlaid
Column 1
Column 2At steady state, variability in peak area < 0.25 %.Steady state can be reached with first elution.
YMC- Bioprocess Group and
column1 column21 0.153 0.1922 0.170 0.1943 0.170 0.1934 0.170 0.1935 0.170 0.1946 0.170 0.1947 0.170 0.194
Average 0.170 0.193error %* 0.1764 0.2169
* does not include the first cycle
PeakArea
45
Continuous capture reproducibility
Customer A using EcoPrime Twin 100 –1g/L titer mAb: 50 g/L load
At steady state, variability of peak area is <1 %.Steady state can be reached with first elution.
5 peaks overlaid
Column 1
Column 2
© YMC Process Technologies.
Column 1 Column 21 0.250 0.2942 0.263 0.2973 0.265 0.2974 0.265 0.2975 0.265 0.297
Average 0.264 0.297error %* 0.639 0.025
* does not include the first cycle
AreaPeak
46
Comparison batch to continuous captureCustomer A - process development run: 1g/L titer mAb
Triple productivity or 67 % less resin and ~ 30% buffer reduction
© YMC Process Technologies.
Case Study #3
© YMC Process Technologies.47
Customer “C”
Reproducibility testing on mAb over multiple cyclesCustomer C
© YMC Process Technologies.48© LEWA - Bioprocess Group
EcoPrime Twin run with 30-h process time
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
Time [h]
Col 1 and 2 UV profiles - Consistent performances over 16 cycles Control state reached at second cycle.
Reproducibility testing on mAb over multiple cyclesCustomer C
© YMC Process Technologies.49© LEWA - Bioprocess Group
EcoPrime Twin run with 30-h process time
Met purity requirements.Variability of peak area less 0.3%
at steady state
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.50
10
20
30
40
50
60
70U
V 28
0 nm
[OD
]
Time [min]
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.50
10
20
30
40
50
60
70
UV
280
nm [O
D]
Time [min]
Peak # Col 1 Col 21 6858 87182 8807 93653 9034 94414 9063 94405 9057 94536 9067 94657 9077 94758 9079 94809 9080 945410 9082 945411 9046 945412 9089 943613 9088 943414 9084 945115 9076 941516 9083 942317 3271 NA
average 9072 9448error [%] 0.1 0.2
Peak Area
Peak#1
Peak#2
Column 1
Column 2
– The result is the new EcoPrime Twin LPLC
– ChromaCon AG and LEWA Collaborate
Customer experience on mAb showsTwin column capture delivers:
51
• Significant productivity gains2-3 times
• Substantial cost or time savingsBetter Protein A utilization
Faster loadingShorter processing timeReduced buffer consumption ..30-50%
• Seamless scale upSame process steps
Proven reproducibility
• Simple 2-column approach and systemAccelerate implementation
Minimize risk
© YMC Process Technologies.
Batch
Tradition batch purification
Traditionalpurification
MCSGP
more pure product
Recycle impure product, extract
pure product
time
Recycle until it’s pure!
R1 R2P
Obtain both high yield and purity with
difficult separations
EcoPrime® Twin process capabilities
52© YMC Process Technologies.
CaptureSMB(2C-PCC)
Utilize the full loading capacity of
your column
40% Protein A cost savings2 x faster processing
Fast capture process and full capacity
utilization of Protein A
Sequential Process
Run two chromatograhic steps without a
stop
Capture and polish or two polishing steps
In-line dilution or buffer modification
High throughputPurification
Bind/elute or flow-through
53© YMC Process Technologies.
Compensates: • Variability in incoming feed titer due to process variability in upstream cell-culture• Reduction of Protein A binding capacity due to exposure to caustics
Dynamic Control Strategies to Accommodate Process Variabilities
AutomAb control strategies implemented as already on Contichrom CUBE
Visit our
Channel
55© YMC Process Technologies Group
YMC logo is a trademark of YMC Co. Ltd.
ChromaCon, Contichrom, ChromIQ and CaptureSMB are registered marks of ChromaCon AG.
Rockwell FactoryTalk is a registered mark of Rockwell Automation.
DeltaV is a registered mark of the Emerson Process Management family of companies.
All goods and services are sold subject to the terms and conditions of sale of the company within YMC which supplies them. A
copy of these terms and conditions is available on request. Contact your local YMC representative for the most current
information.
Subject to change without notice. Data herein does not constitute a guarantee of performance.
© 2018 YMC Process Technologies. – All rights reserved.
Headquarters: YMC Co., Ltd.YMC Karasuma-Gojo Building284 Daigo-cho, Karasuma Nishiiru, Gojo-dori, Shimogyo-ku, Kyoto, 600-8106 JapanTel: +81-75-342-4515 FAX: +81-75-342-4550 [email protected]
YMC Process TechnologiesBio/Pharma Systems’ Group8 Charlestown StreetDevens, MA 01434 Tel: +1 978 487 [email protected]
Regional Offices:www.ymcamerica.comwww.ymc-europe.comwww.india.comwww.ymcchina.comwww.ymckorea.comwww.ymc.sg.comwww.ymctaiwan.com
The future provides broader solutions for our customers
The innovation and growth of this and other EcoPrime product lines has attracted the attention of leading technology suppliers and users. YMC Co., Ltd. assumed all rights and production for the EcoPrime suite of systems in late 2018 from LEWA-Nikkiso America, Inc. This acquisition brings a broad spectrum of chromatographic resins, and columns ideal for large and small molecule purification. More about this new chapter for EcoPrime at www.ymcpt.com.
Ordering information To order the EcoPrime Twin LPLC system, please contact your regional sales representative.
