Novasep Process: TangenX Tangential Flow Filtration Products 1 Strategies for Single Use Tangential Flow Filtration In Biopharmaceutical Applications Michael.
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Novasep Process: TangenX Tangential Flow Filtration Products 1
Strategies for Single Use Tangential Flow FiltrationIn Biopharmaceutical Applications
Michael LaBreckGlobal Product ManagerTangenX TFF Products
2
SiusTM Single Use TFF Cassettes
3
SiusTM family of single-use cassettes Purpose built for single-usePurpose 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
SiusTM and SiusTM-LS Overview
4
Contact Angle Measurement
(water at 20oC)
HyStream
Molecular Weight vs. % Rejection
0102030405060708090
100
0.1 1 10 100 1000 10000
Molecular Weight (kD)
% R
eje
cti
on
1K
3K
5K
10K
30K
50K
100K
300K
0.1um
Membrane Selectivity Curves for:
ProStream Membranes
HyStream Membranes
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
Novasep Process: TangenX Tangential Flow Filtration Products 5
Rejection Characteristics (UF Membranes)
1,000 10,000 100,000
Molecular Weight
0
100%
Per
cent
Rej
ectio
n
Novasep Process: TangenX Tangential Flow Filtration Products 6
Rejection Characteristics (UF Membranes)
1,000 10,000 100,000
Molecular Weight
0
100%
Per
cent
Rej
ectio
n
Novasep Process: TangenX Tangential Flow Filtration Products 7
Rejection Characteristics (UF Membranes)
1,000 10,000 100,000
Molecular Weight
0
100%
Per
cent
Rej
ectio
n
Novasep Process: TangenX Tangential Flow Filtration Products 8
Pore Size Distribution (UF Membranes)
10KD
pore size distribution
Novasep Process: TangenX Tangential Flow Filtration Products 9
Pore Size Distribution (UF Membranes)
Competitor pore size distribution TangenX pore size distribution
10kD 10kD
Novasep Process: TangenX Tangential Flow Filtration Products 10
Flux vs TMP Monoclonal Antibody 1
30 mg/ml Formulation Buffer CF=70ml/min
404550556065707580859095
100
1 1.3 1.6 2 2.5
TMP (bar)
Flu
x (
LM
H) 1 GE
1 Pall
1 NS
1 ML
IBC Applications for BiopharmaceuticalsLa Jolla, CA June 1-3 2009
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LaborLabor
ConsumablesConsumables
WorkflowWorkflow
Single Use TFF Applications
12
LaborLabor
ConsumablesConsumables
WorkflowWorkflow
Single Use TFF Applications
13
Required Steps for TFF process
Set Up
Sanitize
Flush
NWP
Equilibrate
Process
Clean
Flush
NWP
Storage
RE-USABLE TFF
Time
14
Required Steps for TFF process
Set Up
Sanitize
Flush
NWP
Equilibrate
Process
Clean
Flush
NWP
Storage
RE-USABLE TFF
Time
Process = 6 hrs
15
Required Steps for TFF process
Set Up
Sanitize
Flush
NWP
Equilibrate
Process
Clean
Flush
NWP
Storage
RE-USABLE TFF
Time
Process = 6 hrs
Total Time = 12 hrs
16
Process= 6 hrs
Time
Set Up
Equilibrate
Process
Required Steps for TFF process
SINGLE USE TFF
17
Required Steps for TFF process
SINGLE USE TFF
Total Time = 7.0 hrs
Process= 6 hrs
Set Up
Equilibrate
Process
18
Time Allocation Reusable TFF Process
Time Allocation Single Use 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 Savings versus Single Use Cassettes
19
Labor
Consumables
Workflow
Single Use TFF Applications
20
Consumables Include:
Purified Water
Buffers
Cleaning Solutions
Filtration Cassettes
Developing a Model for Single Use TFF
21
Economy of Single Use TFF
75% Less Buffer / WFI Required
230
60
0
50
100
150
200
250
Buffer/WFI Usage
(L/s
q. m
eter
)
Re-useSingle Use
22
Consumables Include:
Purified Water
Buffers
Cleaning Solutions
Filtration Cassettes
Developing a Model for Single Use TFF
23
Reusable Cassette Suppliers
Single Use – Economics
Average = $4,800 / meter2
$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
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80% Less per TFF cassette
Other Supplier Reusable TFF$4,800 per meter2
Single Use – Economics
$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-useSingle use
TangenX SiusTM Single Use TFF$930 per meter2
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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
SiusTM and SiusTM-LS Overview
26
NovaSetTM Reusable TFF Cassettes
Direct Scalability – From Single Use to ReusableSame channel geometry (ΔP and crossflow rate)
Same membrane chemistry (Prostream and Hystream)
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Labor
Consumables
Workflow
Single Use TFF Applications
28
Reduces validation requirementsReduces validation requirements
Process flexibility Process flexibility
Reduces risk of cross-contaminationReduces risk of cross-contamination
Consistent membrane performance run to runConsistent membrane performance run to run
Removes process bottlenecks – Improves workflowRemoves process bottlenecks – Improves workflow
Other Benefits to Single Use TFF
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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
SiusTM and SiusTM-LS Summary
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SiusTM Cassette Holders & Disposable Flow Path Inserts
31
Disposable Flow Path Inserts
Filter Plate Inserts Disposable Flowpath
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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
Disposable Flow Path Inserts
33
TSPDI-VXBC: 10 m² up to 30 m² capacity
TFP99-SP20 Filter Plate Insert (150 LPM)
Disposable Flow Path Inserts
34
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
Disposable Flow Path Inserts
Novasep Process: TangenX Tangential Flow Filtration Products 35
Single Use TFF:Case Study
Novasep Process: TangenX Tangential Flow Filtration Products 36
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
Single Use TFF:Case Study
42
Single Use TFF Case Study
Recombinant Protein
500L Batch Size
10X Concentration / 5 volume Diafiltration
Process Flux = 100 LMH
Process Time = 4 Hours
Membrane Area = 2.5 Sq. Meter
Single Use TFF vs. Reusable TFF
43
Single Use TFF Case Study
Economic Model
20 runs per year
Membrane costs
Labor and Overhead (validation)
WFI and Buffers
Single Use TFF vs. Reusable TFF
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
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Run Number
Cass
ette
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 $ hours $
Set-Up 0.5 $500 0.5 $500Sanitize 0.5 $500
Flush 0.5 $500NWP 0.5 $500
Equilibration 0.25 $250 0.3 $250Process 4.0 $4,000 4.0 $4,000Clean 2.5 $2,500 1.0 $1,000Flush 0.5 $500NWP 0.5 $500Store 0.5 $500
10.25 $10,250 5.75 $5,750
Reusable Single Use
$0
$2,000
$4,000
$6,000
$8,000
$10,000
$12,000Reusable vs. Single-Use Process Cost
1 2Process Type
Cost
(USD
)
Store
NWP
Flush
Clean
Process
Equili.
NWP
Flush
Sanitize
Set-Up
47
Single Use TFF Case Study
Buffer Costs
WFI
Buffer chemicals
Consumables – filters, bags
Labor
QA/QC
Validation
Single Use TFF vs. Reusable TFF
48
Single Use TFF Case Study
Buffer Costs
Buffer Cost $1.20 per literProcess Area 2.5 per m2Number of Runs 20 per campaign
Cost per run Total CostRe-Usable $690 $13,800Single Use $180 $3,600
Note: * Buffer cost includes system, maintainance, buffers, raw materials, monitoring, and disposal
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
Buffe
r Cos
t (U
SD)
49
Single Use TFF Case Study: Summary
Total Cost per Campaign
$0
$50,000
$100,000
$150,000
$200,000
$250,000
1
Tota
l Cos
t
Re-UsableSingle Use
Cost / run Total Cost Cost / run Total CostOverhead & Labor $10,250 $205,000 Overhead & Labor $5,750 $115,000
Buffer Usage $690 $13,800 Buffer Usage $180 $3,600Consumables $500 $10,000 Consumables $2,000 $40,000
TOTAL COST $11,440 $228,800 $7,930 $158,600
Total Savings $70,200
Re-Usable Single Use
50
Single Use TFF Case Study: Summary
45% Increase in Productivity
Process Time
10.25
5.75
0
2
4
6
8
10
12
Hou
rs
Reusable
Single Use
5151
THANK YOU FOR YOUR ATTENTION
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