QUALIFICATION AND VALIDATION DOCUMENT

PROTOCOL
Title:

Qualification of Modified Co-extruded PE/PVC Tubing

Issue Date:

APPROVAL SIGNATURES
Written by:

Reviewed and Approved by:

Property of Doxpub, Inc.

All proprietary rights reserved.

Date

Responsible Department Head

Date

QA/QC Director

Date

Technical Authority

Date

VP Operations

Date

VP Engineering

Date

QVD Protocol

04-0080-PVP-1.0
Page 1 of 17

TABLE OF CONTENTS
page
1.

PURPOSE ..........................................................................................................................................3

2.

ACCEPTANCE CRITERIA ............................................................................................................3

3.

DESCRIPTION AND HISTORY ....................................................................................................3

4.

RESPONSIBILITIES .......................................................................................................................4

5.

REFERENCES AND APPLICABLE DOCUMENTS ...................................................................4

6.

MATERIALS AND EQUIPMENT..................................................................................................5

7.

HEALTH AND SAFETY CONSIDERATIONS ............................................................................6

8.

GENERAL REQUIREMENTS........................................................................................................6

9.

VALIDATION PROCEDURES.......................................................................................................6

ATTACHMENTS
ATTACHMENT #1
ATTACHMENT #2
ATTACHMENT #3
ATTACHMENT #4
ATTACHMENT #5
ATTACHMENT #6
ATTACHMENT #7
ATTACHMENT #8

Preparation of Test Samples ........................................................................10

Tubing Samples - Accelerated Aging Record ..............................................11
Cytotoxicity....................................................................................................12
Permeability Testing .....................................................................................13
Extractables Evaluation ...............................................................................14
Tensile Testing ..............................................................................................15
Solenoid Valve Compatibility Testing ..........................................................16
RF Sealability and Barb Retention Testing .................................................17

Property of Doxpub, Inc.

All proprietary rights reserved.

QVD Protocol

04-0080-PVP-1.0
Page 2 of 17

1.

2.

3.

PURPOSE
1.1

The objective of this protocol is to complete the qualification of a polyvinylchloride and polyethylene
(PE/PVC) co-extruded tubing for the purpose of replacing the current column and precolumn tubing
material of PVC (Tygon S-50-HL). The co-extruded material is being qualified because an inner
lumen of PE prevents PVC from having direct contact with column fluid and thereby eliminating
leaching of PVC plasticizers, which are suspected of causing precipitation due to interaction with salts
in PBS.

1.2

The material being qualified with this protocol is a modified co-extruded PE/PVC tubing similar to the
tubing qualified in 04-0065-PVP-1.0, Qualification of Co-extruded PE/PVC Tubing. The modified
material has a softer outer PVC extrusion which is expected to make the tubing compatible with the
solenoid valves on the <make & model> instrument.

1.3

Upon completion of the qualification tests, questions related to the safety and functionality of the new
tubing in use with the <make & model> system will be answered along with the co-extruded design
feature.

ACCEPTANCE CRITERIA
2.1

Cytotoxicity: All samples must be non-toxic according to Cytotoxicity test parameters.

2.2

Tubing Cutter Evaluation: No new tooling should be required for cutting the co-extruded PE/PVC
tubing. All tubing cuts must be clean and square. No tubing delamination should be visible.

2.3

Permeability Testing: The water vapor transmission rate (WVTR) of the co-extruded PE/PVC tubing
must be equal to or better than the WVTR of the Tygon.

2.4

Extractable DEHP: The amount of measurable DEHP from all test samples and from samples taken
from three lots of tubing shall meet the requirements of ISO Standard 3826 - Determination of
extractable DEHP (< 10 mg/ 100 mL).

2.5

Solenoid Valve Compatibility: All co-extruded PE/PVC tubing samples must pass the static leak
pressure test at 30 psi.

2.6

Tensile Test: The tensile force of the co-extruded PE/PVC tubing must be greater than 10 lb. at 100%
offset yield per Instron TM-32.

2.7

Barb Connection: The pull force of all PC barb connections with the co-extruded PE/PVC tubing must
be greater than 5 lb. per Instron TM-55.

2.8

RF Sealability: The co-extruded PE/PVC tubing shall be RF sealable.

DESCRIPTION AND HISTORY

3.1

The current column and precolumn tubing is made of PVC material (Tygon S-50-HL). After
manufacturing, e-beam irradiation and during stability testing, particulate material was noticed in the
pigtail tubing assembly of columns and precolumns. An investigation of the particulate concluded that
the material is DEHP (DOP) plasticizer which is an additive used to control the durometer of extruded
tubing during manufacture. A description and history of the particulate problem is outlined in 040065-OQR-1.0.

3.2

A co-extruded PE/PVC material was identified as a potential replacement for the current PVC material
used in the precolumn and column tube assembly. The new material consists of a inner lumen of PE
material and outer coating of PVC material. The outer PVC material contributes to the tubing
hardness while the inner PE is in contact with the fluid passing through the column and precolumn.

3.3

During the qualification testing per 04-0065-PVR-1.0, it was determined that the test PE/PVC tubing
material (Natvar 151) failed to meet the acceptance criteria established for solenoid valve

Property of Doxpub, Inc.

All proprietary rights reserved.

QVD Protocol

04-0080-PVP-1.0
Page 3 of 17

compatibility. It was not seen as an acceptable replacement for the tubing used for the precolumn
assembly which is used in conjunction with solenoid valves. The recommendation from 04-0065PVR-1.0 was to continue the investigation with the PE/PVC tubing manufacturer to develop a custom
blend of PE/PVC material that would be compatible with the instrument solenoid valve.
3.4

4.

Samples of a modified PE/PVC tubing material (Natvar 151 with an outer 607 PVC) were received
from the vendor and tested for solenoid valve compatibility. Preliminary testing showed that samples
of this material met the solenoid valve static leak test. This protocol outlines the testing required to
qualify the modified PE/PVC tubing material for use as a replacement for the PVC tubing used on the
precolumn and column, P/N 100176-03 and 100178-03.

RESPONSIBILITIES
4.1

Engineering
4.1.1
4.1.2
4.1.3

4.2

Manufacturing
4.2.1
4.2.2

4.3

Irradiate all test samples.

Natvar
4.6.1

5.

Perform all cytotoxicity testing.

Nicolet Electron Services (NES)

4.5.1

4.6

Review and approval of the QVD protocol and report.

Support the monitoring, coordination, and execution of the qualification tests.

North American Science Associates (NAmSA)

4.4.1

4.5

Review and approval of the QVD protocol and report.

Prepare all test samples used in the qualification studies.

QA/QC
4.3.1
4.3.2

4.4

Preparation of the QVD protocol and report.

Monitor, coordinate, and execute the studies as defined in the protocol with the appropriate
vendors, individuals and departments.
Review of qualification data.

Manufacture the co-extruded PE/PVC tubing.

REFERENCES AND APPLICABLE DOCUMENTS

5.1

The following documents pertain to the preparation of test samples:

5.1.1
5.1.2
5.1.3
5.1.4
5.1.5

DWG 400252-XX, Co-extruded Tubing PE/PVC

PNS 400061-04, Tubing, Med Grade Tygon (.094 ID x .156 OD)
MBR 100098-01, Phosphate Buffered Saline, 0.1% Sodium Benzoate
MBR 100244-01, Tube Assembly, Precolumn
MBR 100245-01, Tube Assembly, Column

Property of Doxpub, Inc.

All proprietary rights reserved.

QVD Protocol

04-0080-PVP-1.0
Page 4 of 17

5.2

The following documents contain information used to develop this protocol:

5.2.1
5.2.2
5.2.3

5.3

The following documents describe test methods that will be used for protocol execution:
5.3.1
5.3.2
5.3.3
5.3.4
5.3.5
5.3.6
5.3.7

6.

04-0065-PVR-1.0, Qualification of Co-extruded PE/PVC tubing

ISO 3826:1993(E), Determination of extractable di-(2-ethylhexyl)phthalate (DEHP)
ENGR 0085, Accelerated Aging Procedure to Simulate Ambient and Cold Storage of Plastic
Components and Packaging

09-0204-SOP-1.0, Calibration, Testing & Maintenance of Instron Model 1011

09-0200-SOP-1.0, Tensile Testing of Tubing Using Instron 1011
09-0071-SOP-1.0, Operation & Maintenance of the Beckman DU 640 Spectrophotometer
Instron TM-32 (Engineering Development Test), Tensile Testing for Tubing Materials
Properties
Instron TM-55 (Engineering Development Test), Tensile Tubing Connection
Instructional Manuals, Instron Series IX Automated Materials Testing System Version 5
Applicable Contract Laboratory Test Protocols and Specifications

MATERIALS AND EQUIPMENT

6.1

The following materials are required for the qualification studies.

Table 1: Materials Required for the Qualification Studies

Materials
30 Co-extruded PE/PVC Tubing w/ Heat Sealed Tubing
Ends (Applicable to first tubing lot only)
30 Co-extruded PE/PVC Tubing w/ Heat Sealed Tubing
Ends (Applicable to second and third tubing lot only)
30 Co-extruded PE/PVC Tubing w/ Barbed Tubing Ends
30 Co-extruded Tygon Tubing w/ Heat Sealed Tubing Ends
30 Co-extruded Tygon Tubing w/ Barbed Tubing Ends
10X PBS
PBS 0.1% Sodium Benzoate
6.2

MBRs Used to Build

100245-01 (Modified)

Quantity
45

100245-01 (Modified)

25 per Lot

100245-01 (Modified)
100245-01 (Modified)
100245-01 (Modified)
100099-01
100098-01

125
45
125
N/A
N/A

The following equipment are required for the qualification studies.

Table 2: Equipment Required for the Qualification Studies

Equipment
INSTRON, Series IX Automated Material Testing System
6.04
VWR 1810IR Oven
MARSH Pressure Gauge 1186ISSR
SARTORIUS Type BA6100 Scale
SEBRA RF Tube Sealer
BECKMAN DU 640 Spectrophotometer
VERSA Minicutter

Property of Doxpub, Inc.

All proprietary rights reserved.

QVD Protocol

Equipment,
Calibration Control
or Serial Number
S/N ####

Calibration
Due Date
4/19

CCN 0566
CCN 1033
CCN 0583
S/N ###
E/N LB-015
E/N PK-012

5
9/30
6/30
N/A
5/31
5/31

04-0080-PVP-1.0
Page 5 of 17