single-use systems for critical process applications
TRANSCRIPT
Single-Use Systems for Critical Process Applications
Mitigating the Risk by Implementing a Two-Step Specific Approach for Integrity and Leak Testing
Nathalie PATHIER - Global Product Manager SUT – Pall Life Sciences
•What does a leak mean for the end-user ? •Which applications are critical ? •How can we reduce the risks ? •Potential approach for integrity and leak testing •Summary
Outline
BioPlan Associates Survey
Graph on this slide showing only the top 10 reasons
What Does A Leak Mean ?
Safety Operator and/or
Environment
Safety Product
Costs Business Impact
Which Applications Are Critical ?
Upstream <2000 L
Downstream <2000 L
Formulation & Filling <200 L
How Can We Reduce The Risks ?
Single Use Systems Manufacturing Quality By Design Approach
Robust Data Storage Supported by a Central Data Management System
Component selection
Component validation
Robust sourcing
Application and technical reviews
Risk assessment
Qualification support
Validated processes for assembly and
irradiation
Transportation, Shelf life studies
Leak testing
QbD Design Development Validation Routine Testing
Typical Work Flow from Manufacturing to Final Disposal
Tested by component
manufacturer
SU components
Tested by SUS provider
Assembly Packaging Irradiation Shipment
Disposal Use Installation
Post-use Test Pre-use Test
Tested by SUS end-user
OPERATOR TRAINING
Work Flow from Manufacturing to Final Disposal – Specific Approach
Point-of-Use Test of SUS
Helium Integrity Test of Biocontainers
Tested by component
manufacturer
SU components
Tested by SUS provider
Assembly Packaging Irradiation Shipment
Disposal Use Installation
Post-use Test Pre-use Test
Tested by SUS end-user
OPERATOR TRAINING
Overview of Leak Test Methods
Factor Helium Integrity Test Pressure Decay Leak Flow
Sensitivity ≥5 µm* ≥ 30 µm** ≥ 30 µm**
Environmental influences
Low Medium (Temperature)
Medium (Temperature)
Volume Impact Low – Medium High Medium
Handling Complex Simple Simple
Test Time Low - Medium Medium Medium * Volume dependent ** Pressure and Volume dependent, without volume reduction by testing between plates
• Main steps – Loading the biocontainer – Pulling vacuum – Helium introduction in
the biocontainer – Measuring Helium
concentration in the chamber
Helium Integrity Testing Principle
Helium Integrity Testing Principle
Helium Integrity Testing Results
• HIT at SUS provider – 5 µm defect can
successfully be detected in 2D biocontainer (50 L) and 3D biocontainer (200 L)
Helium Integrity Testing Results
0
2
4
6
8
10
12
14
50L CONTROL 50L with 5 µmDEFECT
200L CONTROL 200L with 5 µmDEFECT
RATI
O O
F HE
LIU
M L
EAK
RATE
Point-of-Use Leak Test at End Users
Leak test using volume-dosed flow measurement technology
Palltronic® Flowstar LGR Test Instrument
Point-of-Use Leak Test at End Users
Point-of-Use Leak Test at End Users
Palltronic Flowstar LGR video http://www.pall.com/main/biopharmaceuticals/product.page?lid=i5s8um3x
Point-of-Use Leak Test at End Users
Examples of single-use systems successfully tested using Palltronic Flowstar LGR instrument
Specific Approach for Integrity and Leak Testing in Critical Applications
Enhanced risk mitigation by a specific two-steps approach
Approach for Risk Mitigation
Summary
• Single-use technologies maturing – Increased need to reduce risks of losing integrity – Especially in critical applications such as F&F (<200 L)
• Risk mitigation – QbD, qualification and routine tests, training, etc. – Enhanced integrity and leak testing
• Very sensitive method at supplier • Point of use leak testing, post installation & pre-use
•Pall R&D Team – Anil Kumar – Vishwas Pethe
Acknowledgements
Contact: [email protected]