This document discusses single-pass tangential flow filtration (SPTFF) as an alternative to batch ultrafiltration. SPTFF uses multiple membrane filter modules or sections in series to concentrate and diafilter solutions in a single pass, achieving higher conversion than batch systems. It compares SPTFF to batch ultrafiltration, outlines how SPTFF works, and presents testing results demonstrating its performance for intermediate concentration and final formulation of IVIG.

1. Scaling Options
• Existing holders and cassettes
• Operation at lower flows
Post-column (or other
step) concentration
• Reduce or eliminate intermediate
pool tank
Pre-column (or other
step) concentration/
diafiltration
• Desalt before IEX column or virus
prefilter
• Concentrate to increase capacity
and reduce time
Final formulation UF2 step
(post batch UF/DF)
• Avoid working volume limits
• Maintain product quality,
particularly if the product is heated
to overcome viscosity effects
What is SPTFF?
Why use SPTFF?
Where can SPTFF be used?
Single-Pass
Permeate
Feed
Tank
Module
RetentateRetentate
Buffer
Batch
Permeate
Feed PumpModuleFeed Pump
Retentate
RetentateDiafiltrate
Filtrate
Filtrate
Feed
Feed
Feed
Tank
Retentate
Filtrate
Feed
Single-Pass
Permeate
Feed
Tank
Module
RetentateRetentate
Buffer
Batch
Permeate
Feed PumpModuleFeed Pump
Retentate
RetentateDiafiltrate
Filtrate
Filtrate
Feed
Feed
Feed
Tank
Retentate
Filtrate
Feed
Single-Pass
Permeate
Feed
Tank
Module
RetentateRetentate
Buffer
Batch
Permeate
Feed PumpModuleFeed Pump
Retentate
RetentateDiafiltrate
Filtrate
Filtrate
Feed
Feed
Feed
Tank
Retentate
Filtrate
Feed
• Product is sufficiently
concentrated/diafiltered after a
single pass through filter
assembly
• No retentate return needed
• Continuous operation
• Product is not sufficiently
concentrated/diafiltered after a
single pass
• Requires retentate return and
multiple passes through filter
• Batch operation
• Simple operation
-- Constant feed flow & retentate pressure
-- Leverage existing holders
• Simple system design
-- Smaller pump
-- Smaller footprint
-- Low working volume allows higher final concentrations
-- Simplifies product recovery
• Once-through flowpath
-- Run in-line with other unit operations
-- Enables continuous processing
-- Reduces pumping damage for sensitive products
Scale down SPTFF testing
SPTFF sizing with IVIG
How does SPTFF work?
• Batch processing: High feed flux and TFF devices operated in
parallel results in low fluid residence time in membrane channels,
hence low conversion
-- 1 device in series
-- feed flux ~ 6 LMM
-- conversion ~ 15 - 20%
• SP-TFF processing: Increase conversion by increasing fluid
residence time in membrane channels via lower feed flux and
longer channels
-- 1 to 3 (or more) devices in series
-- feed flux ~ 0.5 LMM or less
-- conversion ~ 75 - 90+%
Filtrate
Retentate
Retentate
valve
Filtrate
Feed
Feed Pump
Separate permeate lines for each section
Pf
P1 P2 P3Feed
Tank
Section
1
0.1 m2
Section
2
0.1 m2
Section
3
0.1 m2
• Three Pellicon®
3 PLCTK 0.1m2
cassettes
• Diverter plates
• Recycled retentate/permeates
• Feed flow excursions
• Recovery flush
• Cleaning & NWP recovery
• Conversion
-- Decreases with feed LMH
-- Increases with # in series
-- Decreases with feed g/L
• Sizing
-- feed flux based on
conversion target
-- membrane area based
on batch volume and
process time
How does SPTFF compare
with current batch UF?
• Both use same cassettes and holders (need diverter plates)
• Simplicity comes at a price: e.g. 1.2 - 3X membrane area versus
batch sizing
Application SPTFF Batch UF
Intermediate UF,
19 g/L to 40 g/L
0.82 LMM* 2.7 LMM
Final Formulation UF1,
18 g/L to 73 g/L
0.36 LMM 1.5 LMM
Final Formulation UF2,
77 g/L to 174 g/L
0.18 LMM 0.53 LMM
*LMM = feed flow rate in liters per minute
per total square meters of membrane area.
This is worth it for:
• Plants where product pool volumes have increased beyond
available tank capacities
• Limited plant footprint (no room for batch operation)
• Batch holdup limits final concentration
(can’t get to target product g/L)
Is there an advantage to
using custom SPTFF modules
or systems?
SPTFF cleaning after IVIG
• Repeatable NWP recovery for all 3 cassettes in series after use
with IVIG
Single-Pass
Retentate
1SECTIONS SECTIONS2
1
2
3
Retentate
Filtrate
Filtrate
Feed
Feed
Merck is a trademark of Merck KGaA, Darmstadt, Germany.
Pellicon is a registered trademark of Merck KGaA, Darmstadt, Germany.
All other marks are the property of their respective owner.
© 2016 Merck KGaA, Darmstadt, Germany. All rights reserved.
(Application Note Single-Pass Tangential Flow filtration:
how to optimize, Merck)
Single level
• Horizontal sectioning
• Separator plates
Multiple level
• Vertical sectioning
Acknowledgments
Eva Gefroh, Gislea Ramsey, Elizabeth Goodrich, Willem Kools,
Randy Kirlin, Todd Ireland, Dan Dussault
0.0 0.5 1.0 1.5 2.0 2.5 3.0
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0
2
4
6
8
10
12
14
0%
20%
40%
60%
80%
100%
120%
18-20 g/L 1-sections
18-20 g/L 2-sections
18-20 g/L 3-sections
75 g/L 1-sections
75 g/L 2-sections
75 g/L 3-sections
Conversion
Feed lpm/m2
total
NWP(lmh/psi@25°C)
NWP/WWPpre
NWP section 1 NWP section 2 NWP section 3 NWP/NWPpre average
Pre Post-lgG Clean
0.0 0.5 1.0 1.5 2.0 2.5 3.0
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0
2
4
6
8
10
12
14
0%
20%
40%
60%
80%
100%
120%
18-20 g/L 1-sections
18-20 g/L 2-sections
18-20 g/L 3-sections
75 g/L 1-sections
75 g/L 2-sections
75 g/L 3-sections
Conversion
Feed lpm/m2
total
NWP(lmh/psi@25°C)
NWP/WWPpre
NWP section 1 NWP section 2 NWP section 3 NWP/NWPpre average
Pre Post-lgG Clean
0.0 0.5 1.0 1.5 2.0 2.5 3.0
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
3 sections, unequal
area per section
3 sections, equal
area per section
Conversion
Feed lpm/m2
total
0.0 0.5 1.0 1.5 2.0 2.5 3.0
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0
2
4
6
8
10
12
14
0%
20%
40%
60%
80%
100%
120%
18-20 g/L 1-sections
18-20 g/L 2-sections
18-20 g/L 3-sections
75 g/L 1-sections
75 g/L 2-sections
75 g/L 3-sections
Conversion
Feed lpm/m2
total
NWP(lmh/psi@25°C)
NWP/WWPpre
Pre Post-lgG Clean
Batch
Single Pass Tangential Flow
Filtration (SPTFF)
Jonathan Steen, Herb Lutz, Elizabeth Haacke, Kate Chefer,
EMD Millipore Corporation
Single-Pass
Permeate
Feed
Tank
Module
RetentateRetentate
Buffer
Batch
Permeate
Feed PumpModuleFeed Pump
Retentate
RetentateDiafiltrate
Filtrate
Filtrate
Feed
Feed
Feed
Tank
Retentate
Retentate
valve
Filtrate
Feed
Feed Pump
Separate permeate lines for each section
Pf
P1 P2 P3Feed
Tank
Section
1
0.1 m2
Section
2
0.1 m2
Section
3
0.1 m2
• Sizing is comparable between
equal area sections & in
sections in series
• Equal area sectioning is well
known and in the public
domain