LEWA Bioprocess Technologies –Overview of TFF Systems

LEWA Center Of Excellence for High Purity - Devens, MA, USA

LEWA Bioprocess Technologies – Filtration expertise

LEWA Systems’ Capability

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LEWA ecofoam®

System for metering various blowing

agents in plastic manufacture in

combination with extruders

LEWA EcoPrime®

Chromatography (LPLC & HPLC) systems

with innovative, mechatronic drive and

hygienic diaphragm metering pumps

LEWA odorizing system

LEWA has built odorizing systems for over

40 years, e.g., for natural gas, oxygen,

nitrogen and carbon dioxide

Buffer Inline Dilution

System to mix all ingoing fluids, e.g. prior

to a chromatography system

Nitrogen Generation

Industry-scale, custom-designed

membrane-type package with very low

lifecycle costs

LEWA ISO 5 Station

Designed in concert with customer for bulk

drug substance bottling in an ergonomic

and high purity environment

Chemical Injection Package

Customer specific packages for

chemical injection in the oil and gas

industry

LEWA Bioprocess ProductLEWA Bioprocess Product

LEWA Bioprocess Product

LEWA Bioprocess Product

Membrane Systems

Systems designed and fabricated for clients in

biopharm industry using any suppliers cassette

or cartridges

Downstream Systems by LEWA

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LEWA Process Technologies, Inc. - Products & Services

Developing and Supplying High Purity Systems to Global Biopharma Customers

MF Hollow

Fiber

Clarification

Systems

UF/DF

Cassette

Systems

Automation /

Software /

Controls

Buffer In Line

Dilution

Systems

LPLC / HPLC

Chromatography

Systems

ISO 5

Bottling

Station

Our Offerings

Custom TFF

Specialists.

We design Custom UF and MF

TFF systems based on flat

sheet cassette or hollow fiber

modules.

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LEWA TFF Systems using cassette or hollow fiber formats

Major biopharma’s and OEM both have come to LEWA

for TFF system design.

LEWA remains neutral to a specific membrane style –

giving customers what is optimum for their TFF process.

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TFF: LEWA TFF Cassette System for Process Development

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USA (Biopharma Process

Development facilities).

Delivered 2014

Location

Application

Multiple purification processes in

addition to the TFF skid were

developed for processing of

protein based therapies under

development.

LEWA Process Technologies

original design in concert with

major biopharmaceutical

company. LPT automation,

system design and manufacture.

LEWA solution

TFF Cassette

Custom UF /

TFF with

controls and

tank by LEWA

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UF (TFF) Control Panel

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Application Example: TFF

Ultrafiltration Processing System

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EU, USA, Asia (Multiple

Biopharma Facilities).

Delivered series of units starting

2008

Location

Application

Hollow Fiber Membrane

production skid for GMP

production.

LEWA OEM design for major life

sciences technology supply

company. LEWA Process

Technologies design and

manufacture based on OEM

supplied concept.

LEWA solution

Application Example: Membrane Purification System

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USA (Biopharma Facilitiy).

Delivered 2011

Location

Application

Hollow Fiber Membrane

production skid for GMP

production.

LEWA original design for major

biopharmaceutical company.

Employed LEWA EcoDos pumps

with system design and

manufacture by LPT.

LEWA solution

Application Example: Membrane Purification System

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USA (Biopharma Facilitiy).

Delivered 2010

Location

Application

Hollow Fiber Membrane

production skid for GMP

production.

LEWA original design for major

biopharmaceutical company.

Employed Fristam pumps with

system design and manufacture

by LPT.

LEWA solution

Hollow Fiber Fit

Up Modules

Shown on Skid

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Application Example: Cassette Membrane Purification System

USA (Biopharma Facilitiy).

Delivered 2009

Location

Application

Flatt Sheet Cassette Membrane

production skid for GMP

production.

LEWA original design for major

biopharmaceutical company.

System design and manufacture

by LPT.

LEWA solution

Recent Simple UF System: Manual Control

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Complex UF TFF Skids – No Problem!

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Complete System

Design and

Manufacture to

Support TFF Systems

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Photo Example:

LEWA designed and manufacture

of TFF system supply tank and

controls

Application Example: MF (dead end) Purification Systems by LEWA

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USA (Biopharma Facilities).

Multiple Skids

Location

Applications

Clarification and sterile filtration

using MF cartridges from major

suppliers skid for GMP production.

LEWA original design for major

biopharmaceutical companies.

LEWA solution

The Characteristics of Tangential

Flow Membranes.

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Cross Flow Filtration

Tangential Flow Filtration (TFF)

– Higher filtering capacity than

dead end filters (MF cartridges)

– Most commonly used for cell

harvest, protein concentration,

desalt, buffer exchange, etc.

– Complex process control

Cross Flow

Permeate Flow

Tangential Flow Filtration

Feed (PF)

Retentate (PR)

Permeate (Pf)

Membrane

Tangential

flow

Flux

Crossflow/Shear Rate and Delta P

Cross Flow/Shear Rate is:

– The flow that crosses through membrane surface. It typically

refers to the retentate flow, not the feed flow.

– Tangential Flow (or “Cross flow) cleans the membrane surface

in order to prevent membrane fouling.

– Higher crossflow is needed for dirty sample solutions, and

zero cross flow represent the condition of dead end filtration.

Delta P is:

– The pressure difference between feed and retentate.

– Delta P determines cross flow.

– Crossflow and flow channel height determine shear rate.

Crossflow and Delta P

0

500

1000

1500

2000

0 15 30 45 60 75

Delta P (psi)

Cro

ssflow

(m

l/m

in)

Water

Sample Solution

Flux and TMP

Permeate Flow (Flux) is:

– The flow that passes through membrane.

– It is typically presented in LMH (Liter/M2/Hour).

– Flux is usually higher for clean sample solutions than

dirty sample solution.

– In practice, flux is usually declined with processing time,

but sharp flux decline usually indicates insufficient cross

flow (membrane fouling or gel layer formation).

TMP is:

– The trans-membrane pressure.

– The permeate pressure should be zero unless a half of

the minimum delta P is higher than the required TMP.

Flux and TMP and Cross Flow

0

150

300

450

600

0 15 30 45 60 75

TMP (psi)

Flu

x (

LM

H)

Water

Sample Solution

CF2 (CF1)

CF1

Cross Flow Filtration

FLUX Vs. PROCESSING TIME

0

50

100

150

200

250

0 1 2 3 4 5 6

Time (min)

Flu

x (

LM

H)

Work Flow For LEWA Process Technologies - our Strength, Your Benefit

LPT maintains a full compliment of departments that ensure the project has the right resources

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A clear differentiator from

other ”suppliers”.

– 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

Field

Installation /

Service

4

Subject

Matter

Experts

FAT & Production Facilities

A well equipped FAT (Factory

Acceptance Test) area is an

integral part of LEWA Process

Technologies manufacturing

center of excellence.

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FAT Area

Manufacturing Area

Characterization Laboratory

LEWA Process Technologies

has dedicated space and

resources to characterize our

products for the intended

application.

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Downstream Expertise.

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LEWA Process Technologies

understands downstream and creates

value through reduction in footprint,

batch to batch reproducibility and

precision that results in yield

improvement.

Ingenuity with process integrity is our

commitment.

Thank you!

Visit www.lewapt.com for more information on

LEWA Bioprocess Systems.

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All goods and services are sold subject to the terms and conditions of sale of the company within LEWA which supplies them.

A copy of these terms and conditions is available on request. Contact your local LEWA representative for the most current

information.

© 2017 LEWA Process Technologies – All rights reserved.

For more information: www.lewapt.com

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Ulmer Str.10

71229 Leonberg GERMANY

Tel: +49 7152 14-0

Fax: +49 7152 14-1303

lewa@lewa.de

LEWA Biosystems Production Facility

8 Charlestown Road

Devens, MA 01434 USA

Tel: +978 487 1100

sales@lewapt.com

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Yebisu Garden Place Tower 22nd Floor

20-3, Ebisu 4-Chome, Shibuya-ku

150-6022 Tokyo

Tel: +81 3 3443-3711

Fax: +81 3 3473-4963

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132 Hopping Brook Road

MA 01746 Holliston

Tel: +1 508 429-7403

Fax: +1 508 429-8615

sales@lewa-inc.com

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