novasep process: tangenx tangential flow filtration products 1 strategies for single use tangential...

Novasep Process: TangenX Tangential Flow Filtration Products 1

Strategies for Single Use Tangential Flow FiltrationIn Biopharmaceutical Applications

Michael LaBreckGlobal Product ManagerTangenX TFF Products

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SiusTM Single Use TFF Cassettes

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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

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LaborLabor

ConsumablesConsumables

WorkflowWorkflow

Single Use TFF Applications

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Required Steps for TFF process

Set Up

Sanitize

Flush

NWP

Equilibrate

Process

Clean

Flush

NWP

Storage

RE-USABLE TFF

Time

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Required Steps for TFF process

Set Up

Sanitize

Flush

NWP

Equilibrate

Process

Clean

Flush

NWP

Storage

RE-USABLE TFF

Time

Process = 6 hrs

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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

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Process= 6 hrs

Time

Set Up

Equilibrate

Process

Required Steps for TFF process

SINGLE USE TFF

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Required Steps for TFF process

SINGLE USE TFF

Total Time = 7.0 hrs

Process= 6 hrs

Set Up

Equilibrate

Process

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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

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Labor

Consumables

Workflow

Single Use TFF Applications

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Consumables Include:

Purified Water

Buffers

Cleaning Solutions

Filtration Cassettes

Developing a Model for Single Use TFF

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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

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Consumables Include:

Purified Water

Buffers

Cleaning Solutions

Filtration Cassettes

Developing a Model for Single Use TFF

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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

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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

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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

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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

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TSPDI-VXBC: 10 m² up to 30 m² capacity

TFP99-SP20 Filter Plate Insert (150 LPM)

Disposable Flow Path Inserts

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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

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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

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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

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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

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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

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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

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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

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