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

FeedTank

Module

RetentateRetentate

Buffer

Batch

Permeate

Feed PumpModuleFeed Pump

Retentate

RetentateDiafiltrate

Filtrate

Filtrate

Feed

Feed

FeedTank

Retentate

Retentate valve

Filtrate

Feed

Feed PumpSeparate permeate lines for each section

Pf

P1 P2 P3FeedTank

Section1

0.1 m2

Section2

0.1 m2

Section3

0.1 m2

Single-Pass

Permeate

FeedTank

Module

RetentateRetentate

Buffer

Batch

Permeate

Feed PumpModuleFeed Pump

Retentate

RetentateDiafiltrate

Filtrate

Filtrate

Feed

Feed

FeedTank

Retentate

Retentate valve

Filtrate

Feed

Feed PumpSeparate permeate lines for each section

Pf

P1 P2 P3FeedTank

Section1

0.1 m2

Section2

0.1 m2

Section3

0.1 m2

Single-Pass

Permeate

FeedTank

Module

RetentateRetentate

Buffer

Batch

Permeate

Feed PumpModuleFeed Pump

Retentate

RetentateDiafiltrate

Filtrate

Filtrate

Feed

Feed

FeedTank

Retentate

Retentate valve

Filtrate

Feed

Feed PumpSeparate permeate lines for each section

Pf

P1 P2 P3FeedTank

Section1

0.1 m2

Section2

0.1 m2

Section3

0.1 m2

• 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+%

Single-Pass

Permeate

FeedTank

Module

RetentateRetentate

Buffer

Batch

Permeate

Feed PumpModuleFeed Pump

Retentate

RetentateDiafiltrate

Filtrate

Filtrate

Feed

Feed

FeedTank

Retentate

Retentate valve

Filtrate

Feed

Feed PumpSeparate permeate lines for each section

Pf

P1 P2 P3FeedTank

Section1

0.1 m2

Section2

0.1 m2

Section3

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

AcknowledgmentsEva 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 3.00%

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-sections18-20 g/L 2-sections18-20 g/L 3-sections75 g/L 1-sections75 g/L 2-sections75 g/L 3-sections

Con

vers

ion

Feed lpm/m2 total

NW

P (l

mh/

psi@

25°C

)

NW

P /W

WPp

re

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 3.00%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%3 sections, unequal area per section

3 sections, equal area per section

Con

vers

ion

Feed lpm/m2 total

0.0 0.5 1.0 1.5 2.0 2.5 3.00%

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-sections18-20 g/L 2-sections18-20 g/L 3-sections75 g/L 1-sections75 g/L 2-sections75 g/L 3-sections

Con

vers

ion

Feed lpm/m2 total

NW

P (l

mh/

psi@

25°C

)

NW

P /W

WPp

re

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 3.00%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%3 sections, unequal area per section

3 sections, equal area per section

Con

vers

ion

Feed lpm/m2 total

0.0 0.5 1.0 1.5 2.0 2.5 3.00%

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-sections18-20 g/L 2-sections18-20 g/L 3-sections75 g/L 1-sections75 g/L 2-sections75 g/L 3-sections

Con

vers

ion

Feed lpm/m2 total

NW

P (l

mh/

psi@

25°C

)

NW

P /W

WPp

re

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 3.00%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%3 sections, unequal area per section

3 sections, equal area per section

Con

vers

ion

Feed lpm/m2 total

Batch

Single Pass Tangential Flow Filtration (SPTFF)Jonathan Steen, Herb Lutz, Elizabeth Haacke, Kate Chefer, EMD Millipore Corporation

Single-Pass

Permeate

FeedTank

Module

RetentateRetentate

Buffer

Batch

Permeate

Feed PumpModuleFeed Pump

Retentate

RetentateDiafiltrate

Filtrate

Filtrate

Feed

Feed

FeedTank

Retentate

Retentate valve

Filtrate

Feed

Feed PumpSeparate permeate lines for each section

Pf

P1 P2 P3FeedTank

Section1

0.1 m2

Section2

0.1 m2

Section3

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