Â
K-Prime 40-I, 40-II,
®
and 40-III
Biochromatography
Systems
왘 Broad flow rate range
Small and production scale systems for
expands processing
capabilities developing protein and bio-engineered
왘 New Batch Reporting features product separations requiring flow rates
conform to regulatory from 20 mL to 10 L per minute
requirements
왘 Recipe Editor facilitates
The K-Prime biochromatography systems are designed for separating and
protocol transfers for
clinical trials and small purifying proteins and bio-engineered products. These advanced systems span
scale manufacturing a wide range of flow rates, delivering sharp separations in applications from
small-scale pilot processes through commercial production. All K-Prime systems
왘 Designed for use in small
volume and process are designed to make process scale-up as easy as possible.
development applications as
well as clinical and early
S H E E T
production
Scale-up Overview
D A T A
Development Pilot Production
• Method discovery • Optimize method • Method execution
• Media evaluation • Clinical material • Material manufacturing
• Material prep manufacturing
• Material evaluation
Figure 1. Transferring separations from small to production scale systems is critical in
the success of all new products.
Optimized for Process support a variety of chromatographic system delivers high product recovery
Development, Pilot, and Small techniques, including ion exchange, and purity for cost-effective
to Intermediate Production affinity, hydrophobic interaction and separations. Automated gradient
Scale Applications gel filtration. They accommodate a formation provides exceptional control
Operating at a flow rate of either 20 to broad range of column diameters, for linear and isocratic mixing, which
500 mL/min., 0.1 to 3 L/min. or 1 to depending on the process application. are essential for ensuring precise
10 L/min. and a pressure rating of up elution profiles. Multiple wavelength
to 7 bar (102 psig), the K-Prime Extended Chromatographic sensing improves the system’s capacity
biochromatography systems are de- Capabilities Improve Results to monitor the process stream and
signed for use in process development, Many features, including automated control the elution process.
pilot, clinical trial and production-scale buffer mixing and enhanced UV
manufacturing. These compact systems monitoring, ensure each K-Prime
K-Prime 40-I System K-Prime 40-II System
Absorbance
Absorbance
Time Time
Gradient profile Time HETP (cm) ASYM Gradient profile Time HETP (cm) ASYM
Loading 0% 5 CV 0.031 1.12 Loading 0% 5 CV 0.035 1.15
Elution 0 – 60% 7 CV Elution 0 – 60% 7 CV
Wash & elute 60 – 90% 1 CV Wash & elute 60 – 90% 1 CV
Figure 2. Figure 3.
K-Prime 40-III System
Absorbance
Time
Gradient profile Time HETP (cm) ASYM
Loading 0% 5 CV 0.032 1.2
Elution 0 – 60% 7 CV
Wash & elute 60 – 90% 1 CV
Figure 4.
2
User-friendly CCP®
Automation Software CCP User Interface
The Common Control Platform® ,
(CCP) software, is a robust, industry-
recognized platform used to
accelerate application development
and production. The CCP software
establishes a common platform
capable of controlling and linking
Millipore chromatography and TFF
solutions. It is designed to allow
data to be conveniently archived to
networked systems, and recipes to be
rapidly scaled from developmental
systems to production capacity unit
operations.
The software, through a touch-
screen user-interface, brings push-
button simplicity to the task of
developing and executing complex
and repetitive separation protocols.
In addition, the software:
• Delivers a range of control features
to help you optimize your process.
• Offers full-manual or automatic
control.
• Integrates easily into your plant
network for sharing results and data.
• Includes a powerful Recipe Editor
which allows the user to create
customizable separation recipes
that are configured quickly and
easily.
• Ensures acquisition of all process
data.
• Generates comprehensive batch
reports that meet regulatory
requirements.
In combination with superior
performing hardware built into all
K-Prime systems, the software delivers
a robust and full-featured solution
designed for today’s ultra-pure
separation needs.
3
K-Prime 40-I, 40-II and 40-III
Biochromatography Systems
Complete and Advanced Purification Solutions
for Biopharmaceutical Applications
Technical Innovations in All K-Prime Systems Deliver
Optimized, Robust Chromatographic Performance
Specialized Piping and Valves Offer Efficient and Reliable Separations
The system’s bio-inert pipework is configured to minimize hold-up volume,
eliminate unswept areas and assures system cleanability. All piping and
system components are easily accessible for maintenance and calibration.
The innovative application of unique, three-way, PTFE (Teflon® resin) valves
give the system its versatility and durability. Used in many locations
throughout the system, these specialized valves enable superior process
stream management, eliminate the use of tees, and guarantee extremely long
life. Sturdy, stainless steel connections placed at system boundaries add
robustness and reliability.
Automated Gradient Mixing Allows Precise Separation Control
A gradient mixing system controls both buffer mixing and mixing valve
cycling to form highly accurate and reproducible isocratic or linear gradients.
Mixing valves are positioned before the system pump and are capable of
producing up to 6 different buffer combinations. This methodology ensures
greater precision of absorptive-based chromatographic separations,
lowers processing costs, and reduces reservoir requirements.
Clean Fraction Collection
Users may configure the K-Prime systems
with three, five or ten fraction collection
ports, and fraction waste port. Radial
diaphragm valves assure complete diversion
of all product to the collection vessel and
eliminate the potential for diffusional
contamination that may occur with
weir-diaphragm or other types of
valve arrangements.
Extensive Process Monitoring
Each flow cell is specially designed to ensure complete
passage of all process fluids, resulting in rapid sensor
response and precise system operation. Pre-column
sensors monitor the presence of air, flow, pressure,
pH, conductivity and temperature. Post-column sensors
monitor UV, pH, conductivity and temperature. All
sensing elements are constructed of materials that
conform to FDA guidelines and are contained within
distinct flow cells for easy access and maintenance.
4
Improved Monitoring/Control with High Performance UV Detector
The unique internal geometry of the flow cell ensures accurate
measurement of the entire process stream across a broad range of
absorbance. For improved process monitoring and greater control
K-Prime Systems are capable of monitoring two wavelengths
simultaneously, within a single flow cell. This optional feature broadens
column eluent visibility and improves the capability to fractionate product,
resulting in higher purity and recovery.
Accelerated, Simplified and Dependable Cleaning
An optional three-valve manifold may be added to
the system to either control additional buffer solutions
or control the introduction of cleaning solution during
clean in place (CIP) operations. CIP valves direct
cleaning solutions to each buffer inlet port and
throughout the system. They can either be actuated
manually or controlled via automated cleaning recipe
commands. When the proximity sensor detects the
CIP inlet manifold, the control system automatically
enables the CIP inlets ports for cleaning operations.
This feature assures the system is properly cleaned
prior to resuming separations.
Control Flow Throughout the Separations
The system pump is a highly efficient positive displacement
duplex diaphragm type with an operating flow range of
20–500 mL/min. (40-I), 0.1–3 L/min. (40-II) or
Pictured: K-Prime 40-III System
1 to 10 L/min. (40-III), and maximum discharge pressure
of 7 bar. A high-precision flow meter monitors the flow
during the purification operation, allowing users to
precisely adjust pump speed and flow rate.
Column Protection Ensures Reliable Performance
Each system is equipped with a bubble trap that both prevents air from reaching the
column and dampens flow pulsation. Level sensors monitor air in the bubble trap and
signal the software to both trigger an alarm and shut down the pump in the event of
excess air accumulation. Flow within the bubble trap promotes mixing and prevents
liquid stratification due to variations in liquid density. To avoid sample dilution during
product loading, the bubble trap can be by-passed. The K-Prime 40-III system can be
configured with a stand alone bubble trap or a bubble trap with a separate filter.
5
CCP — State-of-the-Art Tools Monitor Processes and Meets GAMP Standards
Automation Software Compare Batches CCP software was developed in a
CCP software’s batch reporting facility registered to the applicable
Fast, Functional Platform
feature continuously monitors key ISO® 9000 Quality Systems Standard.
The Common Control Platform features
system data to ensure consistent Millipore has adopted and follows
an intuitive, graphical software
processing. Powerful post-run analysis the GAMP guidelines for automated
interface designed to operate and
tools track separation processes and equipment for the pharmaceutical
interface with all K-Prime Systems. It
allow batch-to-batch chromatogram manufacturing industry. Millipore is
allows access to tools used for: de-
comparisons. Functions such as HETP routinely audited by external agencies.
veloping, monitoring, and controlling
and Asymmetry calculations reveal You, the customer, are welcome to visit
complex separation applications;
how well columns are packed prior or audit our manufacturing facilities to
generating comprehensive batch
to separation processing. Copies of observe our Quality Management
reports; and sharing information
batch records may be exported to System in operation.
across a network.
third party programs for further
Multilingual
Quickly Create Separation Protocols analysis.
A multi-language option displays
Using Touch-Sensitive Screens
Customize Recipes Easily the main screen, recipe editor and
A touch-sensitive interactive display
Users may schedule events based on extensive portions of the batch report
allows users to quickly create and
time, volume, column bed volume, or file in eight languages.
launch custom procedures and
any combination of conditional events
operations. Process graphic screens
based on sensor outputs or process-
display a wide range of information
initiated prompts. CCP software
including: active flow path, process
displays the execution status of recipes
sensor readings, alarm status set point
and procedures together with data
values, as well as system-generated
trends and process values that provide
messages.
users with relevant information for
Compliance ready with FDA optimizing their process.
Guideline 21 CFR Part 11 For
Securely Share Your Knowledge
Electronic Records and Electronic
CCP software is OPC2 compliant,
Signatures
Microsoft® Windows® compatable,
The K-Prime systems include CCP
and incorporates the iFIX® SCADA®
software. CCP software’s powerful
technology. Secure access, definable
batch reporting feature meets the
for multiple user levels, allows access
technological requirements of FDA’s
to only those parts of the system
21 CFR Part 111 for electronic
appropriate to user function. Secure
signatures and electronic records.
data acquisition provides a
The batch reporting feature includes
comprehensive audit trail for process
capabilities for electronic signing,
reporting and regulatory compliance.
auditing files, and rendering data
With an optional system-integrated
files unalterable. It utilizes industry
UPS (uninterruptible power supply),
recognized ANSI/ISA-S88.01-1995 1 21 CFR Part 11 provides criteria under which the
recipes downloaded into the PLC FDA will consider electronic records equivalent to
standards for batch operation
and all process data is secure – even paper records and electronic signatures equivalent
nomenclature, and is consistent with to hand-written signatures. It applies to any records
in the event of power failure. in electronic form created, modified, maintained,
the most current industry terminology.
archived, retrieved, or submitted under any agency
records requirement.
2 OPC = OLE for Process Control.
OLE = Object Linking and Embedding
6
Affinity
Fluidized Bed
Media Desalting
Ion Exchange
Gel Filtration Reverse Phase
Fluid Velocity
10 30 50 70 100 200 300 400 500 1000
(cm/hr)
70 70
100 100
140 140
200 200
250 250
Column Diameter (mm)
300 300
350 350
440 440
450 450
630 630
800 800
1000 1000
1200 1200
1400 1400
1600 1600
2000 2000
Legend K-Prime System Flow Rate Recommended Millipore Column
K-Prime 40-I 20 – 500 mL/min QuikScale® Column
K-Prime 40-II 0.1 – 3 L/min Isopak® Column
K-Prime 40-III 1 – 10 L/min
Chromatography Applications Master File numbers) on nearly all proven suitable for biotech and
The K-Prime systems are ideally suited Millipore media. pharmaceutical applications. To ensure
to a broad range of process develop- Millipore columns represent state- the system can be installed and
ment applications and production of-the-art, automated packing and commissioned quickly and reliably,
chromatography applications. media-handling applications. The each unit is subjected to a broad
For more detailed information on columns are ideal for development, range of pre-shipping tests.
system and column sizing, please pilot or production purification in the All test results are recorded and
contact your Millipore Application pharmaceutical biotechnology industry. included within an extensive docu-
Specialist. Sanitary design, ease of assembly, mentation package that accompanies
and pneumatically assisted axial com- each system.
Your Source for All of Your pression make these columns especially System documentation includes:
Chromatography Media and applicable for use with the more rigid, • User documentation
Column Needs higher resolution chromatographic
Millipore specializes in providing media • Materials and chemical
media. For ultimate expansion to
for high-throughput affinity applications compatibility data
industrial process scale, Millipore’s
at process scale. Millipore also provides standard and custom columns range in • Comprehensive system parts list
media for other chromatography tech- size from 70 mm up to two meters in • Sub-component manuals
niques, including normal and reversed diameter. They permit direct scale-up
phase, ion exchange, gel filtration, • Spare parts recommendations
of pilot performance with assurance of
and affinity separations. To optimize continued high efficiency. • Maintenance recommendations
efficiency, capacity and cost, customers
may select media in a range of particle Validation Support and Warranty
and pore sizes. On request, Millipore Documentation The system warranty may be extended
provides customers with full regulatory The K-Prime systems utilize components to a full 2 years, providing one of the
support information (including Drug and process wetted materials that are longest warranties in the industry.
7
Specifications
Flow Rate3 40-I 40-II 40-III
per minute 20–500 mL 0.1–3.0 L 1–10 L
(1.2–30 L/hr)
Pressure Rating Up to 7 Bar (102 psig)
Temperature Range
Ambient: +2 to 30 °C
Flow Stream (temperature
range for operating at
maximum pressure rating): +2 to 30 °C
Process Connection Type 3/4 inch sanitary clamp (accommodates
both 3/4 in. and 1/2 in. fittings)
Pipework Inside Diameter 40-I 40-II 40-III
3 mm bore 10 mm bore 10 mm bore
pre-pump
6 mm bore
post-pump
Buffer/Solvent Inlets Four inlets with gradient capability
Gradient Capability Two component buffer Isocratic or linear
mix; six binary mix combinations
Mix range: 10 – 90% To Place an Order or Receive
Technical Assistance
Accuracy: ± 2% FS of either buffer
For additional information call your
Reproducibility: ± 1%
nearest Millipore office:
Hold-up Volume 40-I 40-II 40-III In the U.S. and Canada,
Buffer to Waste: 75 mL 250 mL 1.45 L call toll-free 1-800-MILLIPORE
Sample to Column: 35 mL 150 mL 1.2 L (1-800-645-5476)
Bubble Trap (Full): 550 mL 550 mL 2.0 L In the U.S., Canada and Puerto Rico,
fax orders to 1-800-MILLIFX
Humidity 5 – 95% (non-condensing) (1-800-645-5439)
Utility Requirements Internet: www.millipore.com
Compressed Air: ≥ 6 bar instrument air filtered to ≤ 5 micron, Technical Service:
– 20 °C dew point, oil free. www.millipore.com/techservice
Maximum Consumption: ~8 L/min (0.3 SCFM)
Electrical Supply 4: Single Phase 100, 120, 240 volts 50/60 Hz
Power Consumption: ~1 kVA
Connection: Push fit socket for 10 mm
OD tube on cabinet Â
Fraction Ports 3 or 5 or 10
Millipore, K-Prime, CCP, Common Control Platform ,
Dimensions 40-I and 40-II 40-III QuikScale and Isopak are registered trademarks of
Millipore Corporation.
Height: 1270 mm (50 in) 1270 mm (50 in) SCADA is a registered trademark of Scada Software
Corporation.
Width: 686 mm (27 in) 686 mm (27 in)
Microsoft and Windows are registered trademarks
Depth: 1042 mm (41 in) 1499 mm (59 in) of Microsoft Corporation.
Teflon is a trademark of E.I. duPont de Nemours and
Uncrated Weight 40-I 40-II 40-III Company.
170 kg 190 kg 260 kg ISO is a registered trademark of the International
(375 lbs) (419 lbs) (573 lbs) Organization for Standardization.
Santoprene is a registered trademark of Advanced
Wetted Materials 316 L SST, PP, EPDM, Teflon resin, PFA, Elastomer Systems.
PVDF, TPX, Quartz, Titanium, Santoprene® CHEM-SURE is a trademark of W. L. Gore &
Associates, Inc.
elastomer and CHEM-SURE™ (K-Prime 40-III
iFIX is a registered trademark of GE Fanuc
only) International, Inc.
Lit. No. DS2004EN00 Rev.A 04/05 05-133
Electrical Enclosure IP 56 (NEMA 4X)
Printed in U.S.A.
© 2005 Millipore Corporation, Billerica, MA.
3 Under specified conditions. Refer to user manual.
All rights reserved.
4 Voltage configured at time of order.
