VG BioWelder® Total Containment SGI5701 ... - Sartorius AG

Validation Guide 

BioWelder ® Total Containment

Table of Contents 

1. Introduction 4 

2. Product Description 5 

2.1 Description 5 

2.2 Operating Principles 5 

2.3 Technical Specifications 5 

2.4 Certifications 5 

3. Validation Tests 6 

3.1 Validation Tests Overview 6 

3.2 Pressure Test 6 

3.3 Tensile Strength Test 7 

3.4 Bacterial Challenge Test 8 

3.5 Stability of Water for Injection 9 

3.5.1 Particle 9 

3.5.2 Extractables 10 

3.5.3 Endotoxin 12 

3.6 Flow Rate Measurement 13 

| 3

1. Introduction 

4 | 

Sartorius Stedim Biotech single-use 

bags and systems are widely used 

in biopharmaceutical processes for 

a variety of unit operations of the 

commercial production of drug 

products such as vaccines, recombinant 

proteins and monoclonal 

antibodies and for the development 

of future biomolecules in clinical 

phases. 

Buffers and media are increasingly 

formulated, sterile filtered 

and stored in single-use Fluid 

Management Systems (FMS) that 

involve Flexel® and Flexboy® Bags 

integrated with filters, impeller 

mixers, tubing, connectors and 

monitoring tools. Product intermediates 

are also filtered and stored 

between UF|DF and chromatography 

purification steps in Gamma 

sterile Fluid Management Systems. 

Fluid Management Systems are 

also adopted for the formulation, 

filtration and aseptic processing of 

final drug products. 

From buffer and media preparation, 

cell culture operations, purification 

operations up to final formulation, 

filtration and transfer, the sterile 

connection is a key element during 

manufacturing processes. 

The BioWelder® Total Containment 

is an innovating device for 

connecting large and liquid 

filled thermoplastic tubing in 

bio pharmaceutical applications. 

The fully automated device allows 

fast and reliable connection in 

sterile welding operations between 

two separate pre-sterilized process 

components. 

The BioWelder® TC is used to 

connect thermoplastic tubing such 

as C-Flex®, PharmaPure®, 

AdvantaFlex®, SaniPure BDF and 

PharMed® BPT, used on disposable 

bags or bag assemblies within 

all biopharmaceutical manufacturing 

processes. BioWelder® TC 

can weld either dry or liquidfilled 

tubing in non classified 

and classified environment while 

maintaining product sterility. 

We have compiled this validation 

guide so that users of the 

BioWelder® TC can plan, implement 

and document their own 

validation procedures.

2. Product Description 

2.1 Description 

The BioWelder® TC is a fully 

automated device for connecting 

thermoplastic tubing in a sterile 

welding operation. 

The fully automated device allows 

sterile connection of liquid 

filled tubing up to 1 inch outer 

diameter. 

The device is programmed with 

standard parameter sets for 

welding C-Flex®, PharmaPure®, 

AdvantaFlex®, PharMed® BPT and 

SaniPure BDF. These parameter 

sets have been validated 

at ambiant temperature. 

2.2 Operating Principles 

The holders, the blade and the tubes 

are inserted into the BioWelder® 

TC. The welding process is fully 

automated and is started via the 

touch screen LCD. The blade is 

first heated up for depyrogenation 

and cooled down to the welding 

temperature. An infrared sensor 

monitors and controls the blade 

temperature during all the welding 

process. When the blade reaches the 

welding temperature, the blade cuts 

the tubes and the new fluid path is 

welded together. 

2.3 Technical Specifications 

Power requirements 230 VAC ±10 % 115 VAC ±10 % 

Input frequency 50 – 60 Hz 

Input current 1.2 – 2.4 A max. 

Operating temperature 5 °C – 40 °C (41 °F – 104 °F) * 

Relative air humidity 20 % – 80 % 

Degree of protection IP20 

Dimensions (L ƒ W ƒ H) [mm] 555 ƒ 261 ƒ 269 

[inches] (21.85 ƒ 10.27 ƒ 10.59) 

Weight [kg] 15.9 (350.53 lb) 

Interface SD Card 

Web browser 

Temperature sensor IR-Termopile 

Validation holder Type K, calibration holder available 

Cutting blade Cr-Ni-Alloy, single-use 

Tube holder size (ID ƒ OD) 

3/8" ƒ 5/8" 

1/2" ƒ 3/4" 

5/8" ƒ 7/8" 

3/4" ƒ 1" 

Welding cycle 1 min 30 – 2 min 30 

(depending on tube diameters and material) 

Standard settings for C-Flex®, PharmaPure®, AdvantaFlex®, 

PharMed® BPT, SaniPure BDF 

Minimum tubing length [mm] 450 

Max. operating pressure validated [bar] 1 

* The device is programmed with standard parameter sets for welding C-Flex®, 

PharmaPure®, AdvantaFlex®, PharMed® BPT and SaniPure BDF. 

These parameter sets have been validated at ambiant temperature. 

2.4 Certifications 

CE 

UL 

WEEE 

RoHS 

| 5

3. Validation Tests 

6 | 

The validation of the BioWelder® 

TC was performed according to 

Sartorius Stedim Biotech standard 

methods. The validation tests were 

performed at ambiant temperature 

on the C-Flex® 374 tubing after 

sterilization. 

3.1 Validation Tests Overview 

Tubing Sterilization (C-Flex® 374) 

Tube Welding 

Visual Inspection 

Pressure Test 

Tensile Strength Test 

Bacterial Challenge Test 

Particle Extractable Endotoxin 

Flow Rate Measurement 

Pressure test and tensile strength 

test are performed to demonstrate 

the robustness of the thermal weld. 

Bacterial challenge test is done 

to demonstrate the ability of the 

BioWelder® TC to maintain the 

product sterility inside the tube 

during welding connection. 

Particle, Extractable and endotoxin 

tests are carried out to check 

that the thermal weld meets the 

specifications given in the section 

“Sterile Water for Injection” of the 

current USP. 

Flow rate measurement test is 

performed to check that the 

thermal weld does not reduce the 

flow rate during fluid transfer. 

3.2 Pressure Test 

Purpose 

The purpose of the pressure test 

is to check the robustness of the 

welding connection. The pressure 

test is performed on the C-Flex® 

374 tubing sterilized under the 

following conditions: 

Test 1: the two tubes are sterilized 

by Gamma irradiation at 50 kGy 

Test 2: the two tubes are sterilized 

by Autoclave 

(1 cycle 121 °C – 20 minutes) 

Test 3: one tube is sterilized by 

Gamma irradiation at 50 kGy and 

one tube is sterilized by autoclave 

(1 cycle 121 °C – 20 minutes) 

Test Method 

For the tests 1, 2 and 3, the tubes 

are first sterilized and filled with 

water. The liquid filled tubings 

are welded together using the 

BioWelder® TC. After a visual check 

of the thermal weld, the tubes are 

immersed into water and tested 

under air pressure at 1 bar for 

30 seconds. 

The test is passed if no air bubble 

appears. 

Results for the Test 1 

(the two tubes are sterilized by Gamma irradiation at 50 kGy) 

Test Samples Sample Quantity Result at 1 bar 

C-Flex® 374 – 3/8" ƒ 5/8" 6 Pass 

C-Flex® 374 – 1/2" ƒ 3/4" 6 Pass 

C-Flex® 374 – 5/8" ƒ 7/8" 6 Pass 

C-Flex® 374 – 3/4" ƒ 1" 6 Pass 


(the two tubes are sterilized by Autoclave (1 cycle 121 °C – 20 minutes)) 


C-Flex® 374 – 3/8" ƒ 5/8" 6 Pass 

C-Flex® 374 – 1/2" ƒ 3/4" 6 Pass 

C-Flex® 374 – 5/8" ƒ 7/8" 6 Pass 

C-Flex® 374 – 3/4" ƒ 1" 6 Pass 


(one tube sterilized by Gamma irradiation at 50 kGy – one tube sterilized by 

Autoclave (1 cycle 121°C – 20 minutes)) 


C-Flex® 374 – 3/8" ƒ 5/8" 6 Pass 

C-Flex® 374 – 1/2" ƒ 3/4" 6 Pass 

C-Flex® 374 – 5/8" ƒ 7/8" 6 Pass 

C-Flex® 374 – 3/4" ƒ 1" 6 Pass

3.3 Tensile Strength Test 

Purpose 

The purpose of the tensile strength 

test is to check the connection 

strength after welding connection. 

The tensile strength test is 

performed on C-Flex® 374 tubing 

sterilized by Gamma irradiation 

at 50 kGy. 

Test Method 

The tubing are first sterilized by 

Gamma irradiation at 50 kGy and 

filled with water. The liquid filled 

tubing are welded together using 

the BioWelder® TC . After visual 

inspection, the tensile strength 

needed to disconnect the welded 

tube is measured. 

Results 

Test Samples Sample Limit Tensile Result 

Quantity Strength [N] 

C-Flex® 374 – 3/8" ƒ 5/8" 6 F > 80 N 375.7 Pass 

C-Flex® 374 – 1/2" ƒ 3/4" 6 F > 80 N 400.3 Pass 

C-Flex® 374 – 5/8" ƒ 7/8" 6 F > 80 N 459.6 Pass 

C-Flex® 374 – 3/4" ƒ 1" 6 F > 80 N 485.1 Pass 

| 7

3.4 Bacterial Challenge Test 

8 | 

Purpose 

The purpose of the Bacterial 

Challenge test is to demonstrate 

the ability of the BioWelder® TC 

to maintain the product sterility 

inside the tube during welding 

connection. 

Test Method 

Test samples are composed by 

C-Flex® 374 tubing plugged at both 

ends. C-Flex® 374 tubing is first 

sterilized by Gamma irradiating at 

50 kGy. Then, the tube is plugged 

on one end and autoclaved to 

ensure it remains sterile. Afterwards, 

The tube is filled aseptically under 

laminar flow with CASO Broth and 

plugged on the other end. 

The blade and the tube wall are 

contaminated with Geobacillus 

stearothermphilus at 10 6 CFU 

per mL. 

The welding connection is 

performed on test samples before 

final incubation at 55 °C for 

14 days. 

Negative and positive control are 

also tested in parallel to confirm the 

bacterial challenge test. Negative 

control is conducted to check the 

aseptic filling conditions. Positive 

control is conducted to prove the 

fertility of the system. 

The Bacterial challenge test passes 

only if no microbial growth is 

observed on both the test samples 

and the negative control and if a 

microbial growth is observed on the 

positive control. 

Results 

Test Samples Sample Quantity Results 

C-Flex® 374 – 3/8" ƒ 5/8" 6 No Growth 



C-Flex® 374 – 3/4" ƒ 1" 6 No Growth 

Negative control 2 No Growth 

Positive control 2 Growth 

Negative Control Test Samples Positive Control 

Gamma Irradiation at 50 kGy of C-Flex® 374 tubing 

Plugging of one side of the tubing 

Autoclave (15 min at 120 °C) of the Test samples to assure sterility of the filled tube 

Negative control 

No microbial growth 

observed on Negative 

controls 

Aseptic filling of the Test samples with CASO Broth 

Plugging of the second end of the Test sample 

Contamination of the blade and the tubing wall 

with Geobacillus stearothermphilus at 10 2 CFU/mL 

Welding connection 

Final incubation of the Test samples at 55 °C for 14 days 

No microbial growth 

observed on Test samples 

Positive control preparation 

with 10 2 CFU/mL per tube 

Microbial growth 

observed on Positive 

control

3.5 Stability of Water for Injection 

Purpose 

The purpose of the tests is to check 

that the thermal weld meets 

the specifications given in the 

section “Sterile Water for Injection” 

of the current USP. 

Test Method 

The tests are performed after 

Gamma irradiation at 50 kGy 

on the following C-Flex® 374 

tubing sizes: 

3/8" ƒ 5/8" 

3/4" ƒ 1" 

The tubes are filled with WFI and 

welded together using the 

BioWelder® TC. 

The following tests are performed 

on the extracted water: 

Particle 

Extractable 

Endotoxin 

Blank samples, composed only by 

tubing without thermal weld, 

are also tested. 

3.5.1 Particle 

The Particle test is performed 

according to the current 

USP < 788 >. 

Test Samples Sample Results 

Quantity Limits (USP ) 

< 25 Particles/mL (> 10 µm) 

< 3 Particles/mL (> 25 µm) 

C-Flex® 374 – 3/8" ƒ 5/8" not welded 1 Pass 

C-Flex® 374 – 3/8" ƒ 5/8" welded 6 Pass 

C-Flex® 374 – 3/4" ƒ 1" not welded 1 Pass 

C-Flex® 374 – 3/4" ƒ 1" welded 6 Pass 

The thermal welds meet the 

requirements set by the current 

USP . 

| 9

3.5.2 Extractables 

10 | 

Total Organic Carbon 

The TOC test is performed according 

to the current USP < 643 >. 



< 500 ppb 


C-Flex® 374 – 3/8" ƒ 5/8" welded 6 Pass 



The thermal welds meet the requirements 

set by the current USP < 643 >. 

Ions 

Testing of chloride, sulfate, 

ammonium and calcium are 

performed according to the current 

USP in the monograph of “Sterile 

Water for Injection”. 

Test Samples Sample Quantity Chloride Sulfate Ammonium Calcium 

Limits NA < 0.5 mg/L No turbidity < 0.3 mg/L No turbidity 

C-Flex® 374 – 3/8" ƒ 5/8" not welded 1 Pass Pass Pass Pass 

C-Flex® 374 – 3/8" ƒ 5/8" welded 6 Pass Pass Pass Pass 

C-Flex® 374 – 3/4" ƒ 1" not welded 1 Pass Pass Pass Pass 

C-Flex® 374 – 3/4" ƒ 1" welded 6 Pass Pass Pass Pass 


requirements set by the current USP 

in the monograph of “Sterile Water 

for Injection”. 

Oxidizable Substances 

Testing of oxidizable substances are 

performed according to the 

current USP in the monograph of 

“Sterile Water for Injection”. 

Test Samples Sample Oxidizable Substances 

Quantity Acceptance Criteria: 

Pink Color 


C-Flex® 374 – 3/8" ƒ 5/8" welded≠ 6 Pass 




requirements set by the current USP 

in the monograph of “Sterile Water 

for Injection”.

Non Volatile Residues 

Non volatile residues are performed 

according to the current USP . 

Test Samples Sample Non Volatile Residues 

Quantity Limits < 15 mg 







USP . 

pH 

pH test is performed according to 

the current UPS . 

Test Samples Sample pH Limits (USP ) 

Quantity 5 < pH < 7 







USP . 

Conductivity 

Conductivity is performed according 

to the current UPS . 

Test Samples Sample Conductivity 


< 5 µS/cm 







USP . 

| 11

3.5.3 Endotoxin 

The Endotoxin test is performed 

according to the current USP 

. 

12 | 



< 0.25 EU/mL 







USP .

3.6 Flow Rate Measurement 

Purpose 

Flow rate measurement test is 

performed to check that the 

thermal weld does not reduce the 

flow rate during fluid transfer. 

Test Method 

C-Flex® 374 tubing is sterilized by 

Gamma irradiation at 50 kGy. 

One test sample is prepared without 

any welding connection and 

another test sample is prepared 

with ten welding connections. 

Each test sample is connected to a 

loop where some water is 

re-circulated into a tank by using a 

pump. For each test sample the flow 

rate and the pressure are measured. 

Results 

Flow Rate Measurement 

Test Samples Flow Rate Flow Rate 

without Welding with 10 Welding 

Connections Connections 

[L/min] [L/min] 

C-Flex® 374 – 3/8" ƒ 5/8" 5.2 5.2 

C-Flex® 374 – 1/2" ƒ 3/4" 5.2 5.2 

C-Flex® 374 – 5/8" ƒ 7/8" 5.2 5.2 

C-Flex® 374 – 3/4" ƒ 1" 5.2 5.2 

Pressure P1 Measurement 

Test Samples P1 differential between Samples with 

10 thermal Welds & without Weld [%] 

C-Flex® 374 – 3/8" ƒ 5/8" 0.6 

C-Flex® 374 – 1/2" ƒ 3/4" 0.4 

C-Flex® 374 – 5/8" ƒ 7/8" < 0.05 

C-Flex® 374 – 3/4" ƒ 1" < 0.05 

Results show that the thermal 

weld does not reduce the flow rate 

during fluid transfer. 

| 13

Sales and Service Contacts 

For further contacts, visit www.sartorius-stedim.com 

Europe 

Germany 

Sartorius Stedim Biotech GmbH 

August-Spindler-Strasse 11 

37079 Goettingen 

Phone +49.551.308.0 

Fax +49.551.308.3289 

www.sartorius-stedim.com 

Sartorius Stedim Systems GmbH 

Schwarzenberger Weg 73–79 

34212 Melsungen 

Phone +49.5661.71.3400 

Fax +49.5661.71.3702 


France 

Sartorius Stedim Biotech S.A. 

ZI Les Paluds 

Avenue de Jouques – BP 1051 

13781 Aubagne Cedex 

Phone +33.442.845600 

Fax +33.442.845619 

Sartorius Stedim France SAS 

ZI Les Paluds 

Avenue de Jouques – CS 71058 

13781 Aubagne Cedex 

Phone +33.442.845600 

Fax +33.442.846545 

Austria 

Sartorius Stedim Austria GmbH 

Franzosengraben 12 

A-1030 Vienna 

Phone +43.1.7965763.18 

Fax +43.1.796576344 

Belgium 

Sartorius Stedim Belgium N.V. 

Leuvensesteenweg, 248/B 

1800 Vilvoorde 

Phone +32.2.756.06.80 

Fax +32.2.756.06.81 

Denmark 

Sartorius Stedim Nordic A/S 

Hoerskaetten 6D, 1. 

DK-2630 Taastrup 

Phone +45.7023.4400 

Fax +45.4630.4030 

Hungary 

Sartorius Stedim Hungária Kft 

Kagyló u. 5 

2092 Budakeszi 

Phone +36.23.457.227 

Fax +36.23.457.147 

Italy 

Sartorius Stedim Italy S.p.A. 

Via dell’Antella, 76/A 

50012 Antella-Bagno a Ripoli (FI) 

Phone +39.055.63.40.41 

Fax +39.055.63.40.526 

Netherlands 

Sartorius Stedim Netherlands B.V. 

Edisonbaan 24 

3439 MN Nieuwegein 

Phone +31.30.6025080 

Fax +31.30.6025099 

Poland 

Sartorius Stedim Poland Sp. z o.o. 

ul. Wrzesinska 70 

62-025 Kostrzyn 

Phone +48.61.647.38.40 

Fax +48.61.879.25.04 

Russian Federation 

OOO "Sartorius ICR" 

Rasstannaya str. 2, b.2, lit.A, 

p/b 134, 

192007, Saint-Petersburg 

Phone +7.812.6100821 

Fax +7.812.6100821 

Spain 

Sartorius Stedim Spain SA 

C/Isabel Colbrand 10, 

Oficina 70 

Polígono Industrial de Fuencarral 

28050 Madrid 

Phone +34.90.2110935 

Fax +34.91.3589623 

Switzerland 

Sartorius Stedim Switzerland AG 

Ringstr. 24 a 

8317 Tagelswangen 

Phone +41.52.354.36.36 

Fax +41.52.354.36.46 

U.K. 

Sartorius Stedim UK Limited 

Longmead Business Park 

Blenheim Road, Epsom 

Surrey KT19 9 QQ 

Phone +44.1372.737159 

Fax +44.1372.726171 


America 

USA 

Sartorius Stedim North America Inc. 

5 Orville Drive 

Bohemia, NY 11716 

Toll-Free +1.800.368.7178 

Fax +1.631.254.4253 

Sartorius Stedim SUS Inc. 

1910 Mark Court 

Concord, CA 94520 

Phone +1.925.689.6650 

Toll-Free +1.800.914.6644 

Fax +1.925.689.6988 

Sartorius Stedim Systems Inc. 

201 South Ingram Mill Road 

Springfield, MO 65802 

Phone +1.417.873.9636 

Fax +1.417.873.9275 

Argentina 

Sartorius Argentina S.A. 

Int. A. Avalos 4251 

B1605ECS Munro 

Buenos Aires 

Phone +54.11.4721.0505 

Fax +54.11.4762.2333 

Brazil 

Sartorius do Brasil Ltda 

Av. Dom Pedro I, 241 

Bairro Vila Pires 

Santo André 

São Paulo 

Cep 09110-001 

Phone +55.11.4451.6226 

Fax +55.11.4451.4369 

Mexico 

Sartorius de México S.A. de C.V. 

Circuito Circunvalación Poniente No. 149 

Ciudad Satélite 

53100 Naucalpan, Estado de México 

Phone +52.5555.62.1102 

Fax +52.5555.62.2942 

Asia|Pacific 

Australia 

Sartorius Stedim Australia Pty. Ltd. 

Unit 5, 7-11 Rodeo Drive 

Dandenong South Vic 3175 

Phone +61.3.8762.1800 

Fax +61.3.8762.1828 

China 

Sartorius Stedim Beijing 

Representative Office 

No. 33, Yu’an Road, 

Airport Industrial Zone B, Shunyi District 

Beijing 101300 

Phone +86.10.80426516 

Fax +86.10.80426580 

Sartorius Stedim Shanghai 

Represantative Office 

Room 618, Tower 1, German Centre, 

Shanghai, PRC., 201203 

Phone +86.21.28986393 

Fax +86.21.28986392.11 

Sartorius Stedim Guangzhou Office 

Room 704, Broadway Plaza, 

No. 233–234 Dong Feng West Road 

Guangzhou 510180 

Phone +86.20.8351.7921 

Fax +86.20.8351.7931 

India 

Sartorius Stedim India Pvt. Ltd. 

#69/2-69/3, Jakkasandra 

Kunigal Road, Nelamangala Tq 

Bangalore – 562 123 

Phone +91.80.4350.5361 

Fax +91.80.4350.5253 

Japan 

Sartorius Stedim Japan K.K. 

KY Building, 8–11 

Kita Shinagawa 1-chome 

Shinagawa-ku 

Tokyo 140-0001 

Phone +81.3.3740.5407 

Fax +81.3.3740.5406 

South Korea 

Sartorius Korea Biotech Co., Ltd. 

8th Floor, Solid Space B/D, 

PanGyoYeok-Ro 220, 

BunDang-Gu 

SeongNam-Si, GyeongGi-Do, 

463-400 

Phone +82.31.622.5700 

Fax +82.31.622.5799 

Malaysia 

Sartorius Stedim Malaysia Sdn. Bhd. 

Lot L3-E-3B, Enterprise 4 

Technology Park Malaysia 

Bukit Jalil 

57000 Kuala Lumpur 

Phone +60.3.8996.0622 

Fax +60.3.8996.0755 

Singapore 

Sartorius Stedim Singapore Pte. Ltd. 

1 Science Park Road, 

The Capricorn, #05-08A, 

Singapore Science Park 2 

Singapore 117528 

Phone +65.6872.3966 

Fax +65.6778.2494 

Specifications subject to change without notice. Printed in Germany on paper that has been bleached without any use of chlorine. 

Publication No.: SGI5701-e12032 · Order No.: 85032-541-89|Ver. 03/2012

VG BioWelder® Total Containment SGI5701 ... - Sartorius AG

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