FluidTechnologySolutions

FULL VALIDATION GUIDE

PureWeld XL tubing

Executive Summary
This is the full validation guide for PureWeld XL tubing. This
guide contains hyperlinks in section 8, page 6 to the reports
which provide the reader with detailed test procedures andactual test results.

Contents

1 Introduction
2 Conditions of use
3 Chemical compatibility
4 Materials, manufacturing and regulatory compliance statements
a.
b.
c.
d.
e.
f.
g.

Materials of construction
Manufacturing environment
Country of origin
Compliance declaration summary
REACH status
RoHS legislation
Storage conditions

5 Compendial and non compendial testing
a.
b.
c.
d.
e.
f.
g.
h.
i.
j.

Summary table
USP <87>
USP <88>
ISO 10993–4
ISO 10993–5
ISO 10993–6
ISO 10993–10
ISO 10993–11
Kligman maximisation
USP <788>

6 Extractables
7 Conclusions

1

1. Introduction
Watson-Marlow’s PureWeld XL (942.) TPE tubing is USP
88 Class VI and ISO 10993 compliant, and produced
from a USP 88 Class VI raw material. It is manufactured
in an ISO 14644-1 class 7 cleanroom. The cleanroom istemperature and humidity controlled, thereby providing astable extrusion environment.
PureWeld XL TPE tubing exhibits a number of key features:• Low particulate generation in peristaltic pumping• Provides exceptional life and accurate flow rates• Sealable and weldable for sterile connectivity• Excellent chemical resistance• Very low extractables, non-toxic and Animal Derived
Component Free (ADCF)• Comprehensive stock of a wide range of sizes
Watson-Marlow Fluid Technology Solutions (WMFTS) is
the world leader in niche peristaltic and sinusoidal pumps
and associated fluid path technologies. Founded on nearly
60 years of supplying engineering and process expertise
and with over one million pumps installed worldwide, ourpumps are tried, tested and proven to deliver. WMFTS is awholly owned subsidiary of Spirax-Sarco Engineering plc(LSE: SPX), a global organisation employing approximately
4,800 people worldwide. Watson-Marlow Fluid Technology
Solutions comprises nine established brands, each with
their own area of expertise, but together offering ourcustomers an unrivalled breadth of solutions for theirpumping applications.

22. Conditions of use
Watson-Marlow’s PureWeld XL (942.) TPE tubing may
be sterilised using:•••Gamma irradiation up to a maximum of
50 kGYAutoclave 1 bar at 121 C/250F
Ethylene Oxide ( EtO)

4. Materials, manufacturing and regulatorycompliance statements
4a Materials of construction
PureWeld XL tubing is a thermoplastic elastomer(TPE) manufactured from a USP 88 Class VI rawmaterial.

4b Manufacturing environment
2a Working temperature

PureWeld is manufactured in an ISO 14644-1 class
7 cleanroom within a facility operating under an
ISO9001 quality management system.

Watson-Marlow’s PureWeld XL (942.) TPE tubing canbe used from -20C ( XF) to + 80C ( XF).

3. Chemical compatibility
A general guide on chemical compatibility of Pureweld
XL tubing can be found on the Watson-Marlow Fluid
Technology Solutions website: wmfts.com/en-us/
support/chemical-compatibility-guide/4c Country of origin
PureWeld XL is manufactured at Bickland Water Road,
Falmouth, Cornwall, United Kingdom, TR11 4RU.

4d Compliance declaration summary
Table 1 details the different substances that are notpresent in the raw material, manufacturing process orfinal composition of PureWeld XL tubing.

Table 1: List of compliance statements for Pureweld XL tubing and substances not present in themanufacture of Pureweld XL
Named substance/compliance statement

Raw material

Manufacturing process

Final productAnimal Derived Content–––

Melamine–––

Phthalates–––

Bisphenol A (BPA)–––Latex–––

Presence of heavy materials–––Allergens–––‘–’ denotes not present or not added
For a complete range of compliance statements relating to PureWeld XL please refer to the compliance guide

4e REACH legislation
All raw materials, compounds used in themanufacturing process and the final PureWeld XL
tubing comply with the REACH regulations.
None of the chemicals used in the manufacture ofPureWeld XL tubing are on the candidate list or thelist of substances of very high concern (SVHC).

4f RoHSIn compliance with the restriction of hazardous
substances (RoHS) directives, no listed substances
are used in the manufacture of PureWeld XL tubing.

34g Storage conditions
To maintain the performance of the components
throughout their lifecycle, they should be stored ina cool, dry environment away from direct sunlightwithout exposure to chemicals and not subjected
to stress. Normal warehouse conditions of 5C−40C(40F−86F) are acceptable. Wherever possible, original
packaging should be maintained. Stock should berotated on a first in, first out (FIFO) basis.
The performance of any component beyond its use
by date, or which has not been stored according
to the recommendations outlined above, cannot beassured.

5. Compendial and non compendial testing

have been evaluated for. Full test methods and results
are available on request. The PureWeld XL tubing was
gamma irradiated at 45–55 kGy prior to testing.

5a Summary table
Table 2 contains a summary of all the compendial
testing and ISO qualifications that PureWeld XL tubing
Table 2: List of compendial and non compendial testing performed
Test reference

Test Description

Result

USP <87>

Biological Reactivity tests, In Vitro, Post Gamma Irradiation samples

PASS

USP <88>

Biological Reactivity tests, In Vivo, Post Gamma Irradiation samples

PASS

ISO 10993-4

Hemolysis

PASS

ISO 10993–5

Biological evaluation of medical devices – part 5: tests for In Vitro cytotoxicity

PASS

ISO 10993–6

Biological evaluation of medical devices, implantation

PASS

ISO 10993–10

Biological evaluation of medical devices, irritation

PASS

ISO 10993–10

Kligman Maximisation testPASS

ISO 10993–11

Biological evaluation of medical devices, systemic toxicity

PASS5b	USP <87> Biological Reactivity tests, InVitro, Post Gamma Irradiation samples
USP 87 determines the biological reactivity of a cell
culture in response to a given test article. Samplesof PureWeld XL tubing were gamma irradiated at45–55 kGy and tested in accordance with USP <87>,
Biological reactivity tests, In Vitro. Extracts, positivecontrol (rubber) and negative control articles wereprepared at 37C (98.6F) for 24 hours. Biologicalreactivity was rated on a scale ranging from Grade 0(no reactivity) to Grade 4 (severe reactivity).
Results: No reactivity was exhibited by thecell cultures when exposed to PureWeld
XL tubing. Therefore they passed therequirements of USP 87 biological reactivity
tests and have no cytotoxic potential.

5c	USP <88> Biological Reactivity tests, InVivo, Post Gamma Irradiation samples
USP Class VI Plastics Test assesses the potential
toxicity of a given test article systemically,
intracutaneously and through implantation. Samplesof PureWeld XL tubing were gamma irradiated at

45–55 kGy and tested in accordance with USP<88>, Biological reactivity tests, In Vivo. This included
the immersion of the test articles in the following
solutions: USP 0.9% sodium chloride, cottonseed oil,
1 in 20 ethanol in NaCl and polyethylene glycol 400 at
70C (158F) for 24 hours.
Results: PureWeld XL tubing extracts andimplants showed no toxicity. Therefore theypassed the requirements of USP <88>
biological reactivity tests.

5d ISO 10993-4 (Hemolysis)
The hemolysis test assesses the potential for indirectcontact of a given sample with blood to cause therupture of erythrocytes (red blood cells).
Samples of PureWeld XL tubing were tested inaccordance with ISO 10993–4, 2002, Biological
Evaluation of Medical Devices – Part 4: Selection ofTests for Interactions with Blood.
Results: PureWeld XL tubing showed no signsof haemolytic activity. Therefore they passed
the requirements of ISO 10993–4.

45e	ISO 10993–5 Biological evaluation of
medical devices – part 5: tests for In Vitrocytotoxicity

is extracted using 0.9% sodium chloride for injection,
cottonseed oil, 1 in 20 ethanol in NaCl or polyethylene
glycol 400 at 70C for 24 hours.

The biological reactivity of a cell culture, in response
to extracts from PureWeld XL tubing was determined.
The maintenance medium on the cell cultures wasreplaced by extracts of PureWeld XL tubing orcontrol article.
The cell cultures were incubated for 48 hours at37±1C (98.6F±33.8F). Biological reactivity wasevaluated by a photo spectrometer at 450 nm
wavelength.

Results: PureWeld XL tubing meet therequirements of ISO 10993–11 guidelines forthe systemic injection test toxicity.

5i	ISO 10993–10 Kligman Maximisation test
The purpose of this test is to detect the allergenic
potential of a test article.
Samples of PureWeld XL tubing were extracted
in USP 0.9% sodium chloride for injection andcottonseed oil at 70C (158F) for 24 hrs and theninjected interdermally. After two weeks, an additional
topical application was introduced to the site ofinterdermal injections.

Results: PureWeld XL tubing showed no signsof cytotoxic potential. Therefore they passed
the requirements of ISO 10993–5.

5f ISO 10993–6 Biological evaluation of 		medical devices, implantation

Results: The sites that were exposed to thetest articles and negative control showedno signs of erythema or edema. Therefore,PureWeld XL tubing are deemed not tocontain any allergic potential.

The purpose of this test is to evaluate the solidmaterial in direct contact with living tissue.
Strips of PureWeld XL tubing (1mm x 1mm x 10mm)
and the negative control plastics were tested. The testsites were examined for inflammation, encapsulation,
necrosis, haemorrhage and discolouration
macroscopically.
Results: PureWeld XL tubing did notdemonstrate any remarkable difference ascompared to the control implant sites when incontact with tissue for 2 weeks. Therefore, itmeet the requirements of the 10993-65g	ISO 10993–10 Biological evaluation of
medical devices, irritation
The intracutaneous test is designed to evaluate local
responses to the extracts of PureWeld XL tubing
following intracutaneous injection. PureWeld XL tubing
is extracted using 0.9% sodium chloride for injection,
cottonseed oil, 1 in 20 ethanol in NaCl or polyethylene
glycol 400 at 70C for 24 hours.
Results: PureWeld XL tubing meet therequirements of ISO10993–10 guidelines forthe intracutaneous injection test.

5h	ISO 10993–11 Biological evaluation of
medical devices, systemic toxicity
The purpose of the systemic injection study isdesigned to screen test articles (PureWeld XL tubing)extracts for potential toxic effects as a result of asingle dose systemic injection. PureWeld XL tubing

55j

USP <788> Particulate testing/			
microscopic particulate count analysis
test
USP Limulus amebocyte lysate (LAL) bacterial
entoxin assay Endotoxins are lipopolysaccharide
complexes in gram negative bacterial cell walls. Thelimulus ameobocyte lysate (LAL) Kinetic Chromogenic
assay is used to determine the quantitative level ofendotoxin present within our products. PureWeld XL
tubing was tested in accordance to the requirementsof USP 85. PureWeld XL (29.0 cm² surface area)
was extracted in 50mL of LAL reagent water at roomtemperature for 60 minutes. LAL-lysate was added
to each sample well on an automated microtiter plate
and then transferred to a plate reader where theabsorbance of each well was read at 405 nm and 37°C at set timepoints. A standard curve was generatedusing software based on reaction time versus
endotoxin concentration which was then compared tothe endotoxin concentration and reaction time of thesample extract.
Results: PureWeld XL extracts had an EU/ml
value of <0.009 EU/cm² which is comparable
to the levels of endotoxin observed in water forinjection.

6. Extractables testing
PureWeld XL tubing connectors were subjected toextraction in multiple solvents at controlled temperatures.
The solvent extracts were then analysed using highpressure liquid chromatography—diode array detectormass spectrometry (HPLC-DAD/MS), Direct injection
Gas Chromatography—Mass spectrometry (DI-GC/MS),
Headspace Gas Chromatography—Mass spectrometry(HS-GC/MS) and Inductively Coupled plasma—Mass
Spectrometry (ICP/MS). HPLC-DAD/MS is used to detect
the presence of non-volatile and UV active extractables. DIGC/MS identifies if there are any semi volatile compounds
present in the extracts whilst volatile extractables can bedetected using HS-GC/MS. Potential elemental impurities
can be identified by ICP-MS.

7. Conclusions
PureWeld XL tubing have been shown to pass a numberof compendial and ISO testing summarised in this guide.
For further information with full compliance statements
and compendial test reports, please contact your WMFTSrepresentative.

8. Hyperlinks to test reports
SectionHyperlink to test data

5b/5e

USP <87> Biological Reactivity tests, InVitro, Post Gamma Irradiation samples;ISO 10993-5 Biological evaluation of
medical devices-part 5: tests for In Vitro
cytotoxicity

5c/5f/5g/5h SP <88> Biological Reactivity tests, InU
Vivo, Post Gamma Irradiation samples;ISO 10993–6 Biological evaluation of
medical devices, implantation; ISO
10993–10 Biological evaluation of
medical devices, irritation; ISO 10993–
11 Biological evaluation of medicaldevices, systemic toxicity

5dISO 10993-4 Haemolysis

5iISO 10993-10 Kligman maximisation

5jUSP <788> Particulate testing/microscopic particulate count analysis
testUSP 85

6Extractables report

The extracts were evaluated for the elemental impurities
listed in the ICH Q3D and USP <232> guidelines.
Results: These studies have shown that there
were extractables indicative of the materialsof construction. WMFTS can provide further
information and assistance in the evaluation ofextractable data for risk assessment purposes.

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Full validation guide: PureWeld XL tubing
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7Disclaimer: The information contained in this document is believed to be correct but Watson-Marlow Limited
accepts no liability for any errors it contains and reserves the right to alter specifications without notice. It is
the users responsibility to ensure product suitability for use within their application. Watson-Marlow, ReNu,
LaserTraceability, Pumpsil, Bioprene, Marprene are registered trademarks of Watson-Marlow Limited.
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