1. Novasep Process: TangenX Tangential Flow Filtration Products
Strategies for Single Use Tangential Flow Filtration
In Biopharmaceutical Applications
Michael LaBreck
Global Product Manager
TangenX TFF Products
Novasep Process: TangenX Tangential Flow Filtration Products

2. SiusTM Single Use TFF Cassettes

3. SiusTM and SiusTM-LS Overview
SiusTM family of single-use cassettes
Purpose built for single-use
Ready to Use - Reduced prep time
Delivered in 0.2M NaOH – Pre-sanitized
Cassette design for Development, Clinical, and Process Scale
SiusTM-LS 0.01 –0.1 m² surface area
SiusTM 0.5 –2.5 m² surface area

4. Contact Angle Measurement
TangenX Membrane Properties
Modified Polyether Sulfone (mPES) membranes currently available
ProStream:
1kD, 3kD, 5kD, 10kD, 30kD, 50kD, 100kD, 300kD
Neutrally Balanced Charge / Low Protein Binding
HyStream:
5kD, 10kD, 30kD, 50kD, 100kD, 300kD, 0.1µm, 0.2µm, 0.45µm, 0.65µm
Hydrophilic - Minimal fouling with hydrophobic molecules / Low Protein Binding
Contact Angle Measurement
(water at 20oC)
HyStream
Membrane Selectivity Curves for:
ProStream Membranes
HyStream Membranes

5. Rejection Characteristics (UF Membranes)
1,000
10,000
100,000
Molecular Weight
100%
Percent Rejection
Novasep Process: TangenX Tangential Flow Filtration Products 5

6. Rejection Characteristics (UF Membranes)
1,000
10,000
100,000
Molecular Weight
100%
Percent Rejection
Novasep Process: TangenX Tangential Flow Filtration Products 6

7. Rejection Characteristics (UF Membranes)
1,000
10,000
100,000
Molecular Weight
100%
Percent Rejection
Novasep Process: TangenX Tangential Flow Filtration Products 7

8. Pore Size Distribution (UF Membranes)
10KD
Novasep Process: TangenX Tangential Flow Filtration Products 8

9. Pore Size Distribution (UF Membranes)
Competitor pore size distribution
TangenX pore size distribution
10kD
10kD
Novasep Process: TangenX Tangential Flow Filtration Products 9

10. IBC Applications for Biopharmaceuticals La Jolla, CA June 1-3 2009
Novasep Process: TangenX Tangential Flow Filtration Products

11. Single Use TFF Applications
Labor
Consumables
Workflow

12. Single Use TFF Applications
Labor
Consumables
Workflow

13. Required Steps for TFF process
RE-USABLE TFF
Set Up
Sanitize
Flush
NWP
Equilibrate
Process
Clean
Storage
Time

14. Required Steps for TFF process
RE-USABLE TFF
Set Up
Sanitize
Flush
NWP
Equilibrate
Process
Clean
Storage
Time
Process = 6 hrs

15. Required Steps for TFF process
Set Up
Sanitize
Flush
NWP
Equilibrate
Process
Clean
Storage
RE-USABLE TFF
Time
Process = 6 hrs
Total Time = 12 hrs

16. Required Steps for TFF process
SINGLE USE TFF
Process= 6 hrs
Set Up
Equilibrate
Process
Time

17. Required Steps for TFF process
SINGLE USE TFF
Process= 6 hrs
Set Up
Equilibrate
Process
Total Time = 7.0 hrs

18. Time Savings versus Single Use Cassettes
Time Allocation Reusable TFF Process
A significant amount of time is spent preparing and cleaning reusable cassettes
Time is used more efficiently when using single-use cassettes
Water usage and utilities are conserved
Time Allocation Single Use TFF Process

19. Single Use TFF Applications
Labor
Consumables
Workflow

20. Developing a Model for Single Use TFF
Consumables Include:
Purified Water
Buffers
Cleaning Solutions
Filtration Cassettes

21. Economy of Single Use TFF
75% Less Buffer / WFI Required
230 60 50
100
150
200
250
Buffer/WFI Usage
(L/sq. meter)
Re-use
Single Use

22. Developing a Model for Single Use TFF
Consumables Include:
Purified Water
Buffers
Cleaning Solutions
Filtration Cassettes

23. Single Use – Economics Average = $4,800 / meter2
Reusable Cassette Suppliers $0
$500
$1,000
$1,500
$2,000
$2,500
$3,000
$3,500
$4,000
$4,500 1
$ per sq meter surface area
Supplier A
Supplier B
Supplier C
Supplier D
Average = $4,800 / meter2

24. $ per sq meter surface area
Single Use – Economics
Other Supplier Reusable TFF
$4,800 per meter2
TangenX SiusTM Single Use TFF
$930 per meter2
$4,800
$930 $0
$500
$1,000
$1,500
$2,000
$2,500
$3,000
$3,500
$4,000
$4,500 1
$ per sq meter surface area
Re-use
Single use
80% Less per TFF cassette

25. SiusTM and SiusTM-LS Overview
Membrane surface areas available
100 cm², 200 cm², 0.1 m²: Process development
0.5 m², 1.5 m², 2.5 m²: Pilot / Process
SiusTM-LS 0.01 –0.1 m² surface area
SiusTM 0.5 –2.5 m² surface area

26. NovaSetTM Reusable TFF Cassettes
Direct Scalability – From Single Use to Reusable
Same channel geometry (ΔP and crossflow rate)
Same membrane chemistry (Prostream and Hystream)

27. Single Use TFF Applications
Labor
Consumables
Workflow

28. Other Benefits to Single Use TFF
Reduces validation requirements
Process flexibility
Reduces risk of cross-contamination
Consistent membrane performance run to run
Removes process bottlenecks – Improves workflow

29. SiusTM and SiusTM-LS Summary
Pre-sanitized, 100% Integrity Tested
Equilibrate and ready-to-use
Reduce Labor by 50%
Reduce Buffer / WFI by 75%
Full range of formats and pore sizes

30. SiusTM Cassette Holders & Disposable Flow Path Inserts

31. Disposable Flow Path Inserts
Filter Plate Inserts
Disposable Flowpath

32. Disposable Flow Path Inserts
Filter Plate Inserts (TFP75-SE16)
0.5 to 5.0 meter2
(up to 49 LPM)
Disposable
Pre-sanitized
USP Class VI Polypropylene
1” TC (4) ports
Low cost SS Holder

33. Disposable Flow Path Inserts
TSPDI-VXBC: 10 m² up to 30 m² capacity
TFP99-SP20 Filter Plate Insert (150 LPM)

34. Disposable Flow Path Inserts
Filter Plate Inserts – LS (TFPLS-SA08)
0.01 m2 to 0.1 m2 x 5
Disposable
Pre-sanitized
USP Class VI Polypropylene
3/4” mini TC or luer lock
Low cost SS Holder

35. Novasep Process: TangenX Tangential Flow Filtration Products
Single Use TFF:
Case Study
Novasep Process: TangenX Tangential Flow Filtration Products

36. Novasep Process: TangenX Tangential Flow Filtration Products
Michael Xenelis, EMD Serono Biotech Center
IBC Bioprocess International Conference
October 16, 2009
Novasep Process: TangenX Tangential Flow Filtration Products

37. Novasep Process: TangenX Tangential Flow Filtration Products

38. Total Process Time = 13.1 Hours
Novasep Process: TangenX Tangential Flow Filtration Products

39. Novasep Process: TangenX Tangential Flow Filtration Products

40. Novasep Process: TangenX Tangential Flow Filtration Products

41. Novasep Process: TangenX Tangential Flow Filtration Products
Single Use TFF:
Case Study
Novasep Process: TangenX Tangential Flow Filtration Products

42. Single Use TFF Case Study
Single Use TFF vs. Reusable TFF
Recombinant Protein
500L Batch Size
10X Concentration / 5 volume Diafiltration
Process Flux = 100 LMH
Process Time = 4 Hours
Membrane Area = 2.5 Sq. Meter

43. Single Use TFF Case Study
Single Use TFF vs. Reusable TFF
Economic Model
20 runs per year
Membrane costs
Labor and Overhead (validation)
WFI and Buffers

44. Single Use TFF Case Study
Membrane Costs
Run # vs. Cassette Cost / Run $0
$1,000
$2,000
$3,000
$4,000
$5,000
$6,000
$7,000
$8,000
$9,000
$10,000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Run Number
Cassette Cost per Run
Re-Usable
Single Use

45. Single Use TFF Case Study
Labor and Overhead
Labor
QA / QC
Validation
Facilities – HVAC, Clean Room

46. Single Use TFF Case Study
Labor and Overhead
Labor and Overhead Rate
$1,000/hr
hours $
Set-Up
0.5
$500
Sanitize
Flush
NWP
Equilibration
0.25
$250
0.3
Process
4.0
$4,000
Clean
2.5
$2,500
1.0
$1,000
Store
10.25
$10,250
5.75
$5,750
Reusable
Single Use $0
$2,000
$4,000
$6,000
$8,000
$10,000
$12,000
Reusable vs. Single-Use Process Cost 1 2
Process Type
Cost (USD)
Store
NWP
Flush
Clean
Process
Equili.
Sanitize
Set-Up

47. Single Use TFF Case Study
Single Use TFF vs. Reusable TFF
Buffer Costs
WFI
Buffer chemicals
Consumables – filters, bags
Labor
QA/QC
Validation

48. Single Use TFF Case Study
Buffer Costs
Buffer Cost per Campaign
$13,800
$3,600 $0
$2,000
$4,000
$6,000
$8,000
$10,000
$12,000
$14,000
$16,000
Re-Usable
Single Use
Buffer Cost (USD)
Buffer Cost
$1.20
per liter
Process Area
2.5
per m2
Number of Runs 20
per campaign
Cost per run
Total Cost
Re-Usable
$690
$13,800
Single Use
$180
$3,600
Note: * Buffer cost includes
system, maintainance, buffers,
raw materials, monitoring, and
disposal

49. Single Use TFF Case Study: Summary
Cost / run
Total Cost
Overhead & Labor
$10,250
$205,000
$5,750
$115,000
Buffer Usage
$690
$13,800
$180
$3,600
Consumables
$500
$10,000
$2,000
$40,000
TOTAL COST
$11,440
$228,800
$7,930
$158,600
Total Savings
$70,200
Re-Usable
Single Use
Total Cost per Campaign $0
$50,000
$100,000
$150,000
$200,000
$250,000 1
Total Cost
Re-Usable
Single Use

50. Single Use TFF Case Study: Summary
45% Increase in Productivity
Process Time
10.25
5.75 2 4 6 8 10 12
Hours
Reusable
Single Use

51. THANK YOU FOR YOUR ATTENTION51 51