REPLIGEN XCell ATF 2 Manuale utente

SG-SSATF24 rev 1

For Use with:

•XCell® ATF 2 Stainless Steel Housing

•XCell® ATF 4 Stainless Steel Housing

XCell® ATF 2 and 4

Stainless Steel Housings

User Guide

KrosFlo® TFDF™ Lab System

User Guide

XCell® ATF 2 and 4 Stainless Steel Housings

User Guide

SG-SSATF24 rev 1

The information contained in this document is subject to change without notice.

With respect to documentation accompanying product, Repligen makes no warranty, express or

implied. Any and all warranties related to the documentation accompanying product are expressly

disclaimed. Customer shall refer to the terms and conditions of sale governing the transaction for

any and all warranties for the product.

Repligen Corporation shall not be liable for errors contained herein or for incidental or

consequential damages in connection with the furnishing, performance, or use of this material.

No part of this document may be photocopied, reproduced, or translated to another language

without the prior written consent of Repligen Corporation.

Products are not intended for diagnostic or therapeutic use or for use in vivo with humans or

animals.

For further information, please contact Repligen Corporation at www.repligen.com.

of Repligen Corporation and/or its affiliate(s) or their respective owners.

Customer Support

customerserviceUS@repligen.com

+1-800-622-2259 (Option 1)

Repligen Corporation

111 Locke Drive

Marlborough, Massachusetts 01752

www.repligen.com

KrosFlo® TFDF™ Lab System

User Guide

XCell® ATF 2 and 4 Stainless Steel Housings

User Guide

SG-SSATF24 rev 1

Contents

6.1.1 Installing the diaphragm .............................................................................................10

6.2.1 XCell® ATF 2 Stainless Steel Housing hollow fiber filter installation...........................11

6.3.1 Filter wetting...............................................................................................................12

6.3.2 Integrity testing pre-autoclaving ................................................................................12

6.3.3 Autoclaving .................................................................................................................12

6.3.4 Integrity testing post-autoclaving...............................................................................12

6.4.1 XCell® ATF 2 Stainless Steel tubing set kits and accessories.......................................13

6.4.2 Tubing set kit for XCell® ATF 2 Stainless Steel Housing connected to glass bioreactor

6.5.1 Removing the housing from the bioreactor ...............................................................15

6.5.2 HFF Removal ...............................................................................................................15

6.5.3 Decontaminating the HFF for Disposal .......................................................................15

6.5.4 Pump Air Inlet Filter, O-Rings, Gaskets, and Quick Connects.....................................15

7.1.1 Installing the diaphragm .............................................................................................16

7.1.2 XCell® ATF 4 Stainless Steel Housing hollow fiber filter installation...........................17

7.2.1 Pressure testing ..........................................................................................................18

7.2.2 Filter wetting...............................................................................................................18

7.2.3 Integrity testing pre-autoclaving ................................................................................18

7.2.4 Autoclaving .................................................................................................................18

7.2.5 Integrity testing post-autoclaving...............................................................................18

7.3.1 XCell® ATF 4 Stainless Steel Housing tubing set kits and accessories.........................19

7.3.2 Tubing set kit for XCell® ATF 4 Stainless Steel Housing connected to glass bioreactor

7.4.1 Removing the housing from the bioreactor ...............................................................21

7.4.2 HFF Removal ...............................................................................................................21

8.3.1 EU Declaration of Conformity.....................................................................................22

8.3.2 Tube set kits................................................................................................................23

KrosFlo® TFDF™ Lab System

User Guide

XCell® ATF 2 and 4 Stainless Steel Housings

User Guide

SG-SSATF24 rev 1

List of tables

Table 1. Explanation of user attention phrases ......................................................................................8

Table 2. Explanation of symbols .............................................................................................................8

Table 3. Dimensions................................................................................................................................9

Table 4. Suggested scale of operation ....................................................................................................9

Table 5. Headplate fitting part numbers...............................................................................................13

Table 6. XCell® ATF 2 tubing set kit options..........................................................................................13

Table 7. XCell® ATF 2 required accessories...........................................................................................13

Table 8. Headplate fitting part numbers...............................................................................................19

Table 9. XCell® ATF 4 tubing set kit options..........................................................................................19

Table 10. XCell® ATF 4 required accessories.........................................................................................19

Table 11. XCell® ATF 2 spare parts........................................................................................................23

Table 12. XCell® ATF 4 spare parts........................................................................................................24

List of figures

Figure 1. Pressure and exhaust strokes ..................................................................................................8

Figure 2. XCell® ATF 2 Stainless Steel Housing......................................................................................10

Figure 3. Orientation of silicone diaphragm in XCell® ATF 2 Stainless Steel Housing ..........................11

Figure 4. XCell® ATF 2 Stainless Steel Housing Installation of HFM......................................................11

Figure 5. XCell® ATF 2 Stainless Steel Housing connection to glass bioreactor (tri-clamp)..................14

Figure 6. XCell® ATF 2 Stainless Steel Housing connection to glass bioreactor

(AseptiQuik®/ReadyMate™).........................................................................................................14

Figure 7. XCell® ATF 4 Stainless Steel Housing......................................................................................16

Figure 8. Orientation of silicone diaphragm in XCell® ATF 4 Stainless Steel Housing ..........................17

Figure 9. XCell® ATF 4 Stainless Steel Housing connection to glass bioreactor (tri-clamp)..................20

Figure 10. XCell® ATF 4 Stainless Steel Housing connection to glass bioreactor (AseptiQuik®)...........20

KrosFlo® TFDF™ Lab System

User Guide

XCell® ATF 2 and 4 Stainless Steel Housings

User Guide

SG-SSATF24 rev 1

Abbreviations

A2B ATF device to bioreactor

A2C ATF device to controller

ATF Alternating tangential flow

DAC Disposable aseptic connectors

DF Driving force

DP Driving pressure

E Exhaust

FAS Field Applications Specialist

HFF Hollow fiber filter

HFM Hollow fiber module

hr Hour

kD kilodalton

L Liter

Lbs Pounds

m Meter

M Molar

min Minute

mm millimeter

NaOH Sodium hydroxide

P Pressure

PA Pump air hemisphere

PES Polyethersulfone

PL Pump liquid hemisphere

ppm Parts per million

PRV Pressure regulator valve

PS Polysulfone

psi Pounds per square inch

psig Pounds per square inch gauge

SIP Steam in Place

SUB Single-use bioreactor

µm micron

California Proposition 65 Warning

Warning

This product can expose you to chemicals including lead, which is

known to the State of California to cause cancer and birth defects or

other reproductive harm. For more information, go to

www.P65Warnings.ca.gov/product.

XCell® ATF 2 and 4 Stainless Steel Housings

User Guide

SG-SSATF24 rev 1

1. Introduction

XCell® ATF Technology uses alternating tangential flow (ATF) to intensify upstream processes by

retaining cells in suspension cultures, such as mammalian cell culture and viral vectors. An

innovative diaphragm pump creates alternating tangential flow, leading to high viable cell densities

and increased throughput with lower cost of goods. Typical applications include intensification of

the following processes:

•N-1 fed-batch

•Long-term continuous processing

•Vaccine and virus production

•Gene therapy and media exchange

XCell® ATF 2 and XCell® ATF 4 Stainless steel Housings enable production of high density, high

viability cell culture applications with linear flux and low shear for scale-up to 50 L. The stainless

steel product line includes the housings, XCell® Lab Controllers, software, tubing set kits, pressure

sensors, and accessories.

Hollow fiber filters (HFF) used in XCell® ATF Technology are made of Polyethersulfone (PES) or

polysulfone (PS) and are available in 0.2 and 0.5 µm and 50 kD pore size and 1 mm inner diameter

and are scalable across device sizes.

Single-use tubing set kits and accessories are available for the connection of XCell® ATF 2 and 4

Stainless Steel Housings to both glass and single-use bioreactors, simplifying preparation and

connectivity and allowing for the proper exchange of cell culture material. XCell® Lab Controllers

operate the diaphragm pumps. The housings and tubing set kits are also compatible with legacy C24

Controllers. Additional information on the use of the controllers and XCell® ATF Technology can be

found in XCell® Lab Controller User Guide.

This document describes the major components, set-up, connectivity, and preparation of the glass

XCell® ATF 2 and 4 Housings and hollow fiber filters. Users should possess a basic level of skill in the

areas of aseptic technique and fluid handling.

For further support in optimizing or troubleshooting, please contact your local Repligen Field

Applications Specialist (FAS).

XCell® ATF 2 and 4 Stainless Steel Housings

User Guide

SG-SSATF24 rev 1

2. Description of XCell® ATF Stainless Steel Housings

XCell® ATF Technology includes two sizes of housings to support a fully scalable process. An

integrated diaphragm pump provides alternating tangential flow through a hollow fiber filter which

retains large components (i.e., cells) and removes waste or product components (permeate/filtrate).

An additional pump continuously removes cell-free permeate from the system.

2.1 Components

•Filter housing: XCell® ATF 2 utilizes a fully encapsulated hollow fiber membrane that is

attached above the stainless steel diaphragm pump. XCell® ATF 4 includes a stainless steel

housing that holds the hollow fiber filter.

•Diaphragm pump: spherical housing in which a silicone diaphragm membrane is inflated and

deflated by pressurized air or vacuum, creating alternating flow.

•XCell® ATF to Bioreactor (A2B) connection assembly: tubing assembly connecting the

filtration assembly to a bioreactor or process vessel.

•Bioreactor adapter: adapter between the connection assembly and bioreactor port. Typical

fittings for glass bioreactors include Ingold or tri-clamp. Single-use bioreactors (SUB) use

disposable, aseptic connectors.

Note: Bioreactor adapter is not provided.

•Hollow fiber membrane (HFM) or hollow fiber filter (HFF): 0.2 or 0.5 µm or 50 kD pore size

filter, positioned between the bioreactor and the diaphragm pump.

•Filtrate/harvest tubing: sterile tubing and fittings connecting the housing to the collection

vessel. Compatible with a filtrate/harvest pump.

Note: Filtrate/harvest tubing and pump are not provided.

2.2 XCell® ATF Housing pump cycle

The diaphragm pump generates alternating tangential flow (ATF) through the hollow fiber filter. ATF

is a pulsating, reversible flow of liquid between a process vessel and diaphragm pump.

The process consists of two cycles (Figure 1), the pressure cycle (P-cycle) and the exhaust cycle (E-

cycle). The P cycle occurs when air is fed into the ATF pump, moving the diaphragm up towards the

pump liquid-side (PL) hemisphere and driving the liquid from the diaphragm pump through the HFF

and into the process vessel.

The E-cycle occurs when vacuum is introduced, thus pulling the diaphragm down towards the pump

air-side (PA) hemisphere, and liquid is pulled from the process vessel through the HFF, and back into

the diaphragm pump. The diaphragm must travel between the two extremes to complete one cycle.

The flow through the hollow fiber filter generates tangential flow in each direction in an alternating

fashion.

XCell® ATF 2 and 4 Stainless Steel Housings

User Guide

SG-SSATF24 rev 1

Figure 1. Pressure and exhaust strokes

Note: XCell® ATF Stainless Steel Housings require a vacuum (negative pressure) to move the

diaphragm to its lowest position. Positive pressure from the bioreactor is insufficient to

completely deflate the diaphragm, necessitating the use of vacuum to ensure proper

XCell® ATF Stainless Steel Housing operation.

3. About this document

Several user attention phrases are used throughout this manual. Each phrase should draw the

following level of attention:

Table 1. Explanation of user attention phrases

Phrase Description

Note: Points out useful information

IMPORTANT

Indicates information necessary for proper

instrument operation

CAUTION

Cautions users regarding potentially hazardous

situations regarding user injury or damage to the

instrument if the information is not heeded

WARNING!

Warns users that serious physical injury can result if

warning precautions are not heeded

4. Safety precautions

Table 2. Explanation of symbols

Symbol Description

Caution

Risk of danger. Consult Operating Instructions for nature of hazard and

corrective actions. Potentially hazardous situation which, if not avoided, may

result in property/equipment damage

Safety

Alert

Symbol

Hazard to personnel is present, the safety alert symbol is omitted when the

hazard is related to property/equipment damage only

From bioreactor

To bioreactor

Filtered harvest

HFF

Diaphragm

Positive air pressure

Negative air pressure

Filtered harvest

XCell® ATF 2 and 4 Stainless Steel Housings

User Guide

SG-SSATF24 rev 1

5. Specifications

5.1 Utility requirements

Utility requirements for the XCell® ATF 2 and 4 Systems can be found in the XCell® Lab Controller

User Guide.

Table 3. Dimensions

Filtration Assembly Dimensions1H, W Nominal footprint (m2)

XCell® ATF 2 SS Pump Housing

30", 5"

0.04

XCell® ATF 4 SS Pump Housing

21", 8"

0.13

1Indicated dimensions are estimates for the filtration assembly, as the choice of cartridge and the

connection to the bioreactor and accessories can affect height and effective area.

Housing selection depends on the perfusion rate or total volume throughput in addition to other

process conditions (Table 4).

Table 4. Suggested scale of operation

Housing Bioreactor size

XCell® ATF 2 2 - 10 L

XCell® ATF 4 10 - 50 L

XCell® ATF 2 and 4 Stainless Steel Housings

User Guide

SG-SSATF24 rev 1

6. XCell® ATF 2 Stainless Steel Housing

XCell® ATF 2 Stainless Steel Housing (Figure 2) is recommended for use with 2 - 10 L bioreactors. The

assembly of the housing and accessories includes installing the diaphragm into the housing,

connecting the hollow fiber filter to the housing, and connecting the filter to the bioreactor and the

harvest vessel. The system is prepared for use by filter wetting, integrity testing, and autoclaving.

Figure 2. XCell® ATF 2 Stainless Steel Housing

6.1 Stainless steel XCell® ATF 2 Housing assembly

XCell® ATF 2 Stainless Steel Housing assembly includes installation of the diaphragm and hollow fiber

filter and connection of the tubing from the housing to the bioreactor and the housing to the harvest

vessel.

6.1.1 Installing the diaphragm

Important: The silicone diaphragm must be replaced after each run and prior to sterilization. To

avoid premature failure, it is important to ensure that the diaphragm is seated in the correct

orientation. Use with aqueous liquids only. For use with other fluids contact Repligen for a technical

discussion. When used as instructed, the diaphragm is designed to last over one million

pressure/exhaust cycles.

1. Hollow fiber membrane

2. Permeate/harvest

3. Retentate

4. Diaphragm pump

5. Air inlet

6. Drain port

Questo manuale è adatto per i seguenti modelli

Indice

Altri manuali REPLIGEN Sistema di filtraggio dell'acqua

REPLIGEN

REPLIGEN TangenX SIUS PD Manuale utente

Manuali Sistema di filtraggio dell'acqua popolari di altre marche

Wisy

Wisy LineAir 100 Manuale utente

Schaffner

Schaffner Ecosine FN3446 Series Manuale operativo

Pentair

Pentair FLECK 4600 SXT Guida utente

H2O International

H2O International H20-500 Manuale utente

Renkforce

Renkforce 2306241 Manuale utente

Neo-Pure

Neo-Pure TL3-A502 Manuale utente

FLTR

FLTR OBF Manuale utente

STA-RITE

STA-RITE VERTICAL GRID DE FILTERS S7D75 Manuale utente

Applied Membranes

Applied Membranes W-G844EM Manuale utente

BEGA

BEGA 116 Manuale utente

WATA

WATA Standard Manuale utente

Price

Price FFU series Manuale

Gaggenau

Gaggenau BRITA INTENZA 467873 Manuale utente

Brita

Brita SAFF-100 Manuale utente

HEISSNER

HEISSNER FPU24000-00 Manuale utente

BGS technic

BGS technic 1518 Manuale utente

Reverse Osmosis

Reverse Osmosis RF Series Manuale utente

ubbink

ubbink Filtramax Series Manuale utente