USD3273a

Pall Helium Integrity Test for Allegro™

Single-Use Systems

Supplier high sensitivity integrity test for single-use

systems used in critical applications for enhanced
patient safety
Single-use technologies have gained strong market acceptance in both clinical and
manufacturing operations. Nevertheless, patient safety, as well as protection of operator
and facility must be secured. A suitable strategy to assure the integrity of the single-use
system during the life cycle is essential. This strategy includes the manufacturing process
and the supply chain.

The helium integrity test (using Pall HIT™ technology) provides the highest level of control
that the single-use system leaving the factory is 100% integral. The size of detectable defects
is correlated to microbial ingress. The test can be requested for Allegro biocontainer systems,
Allegro mixer biocontainer systems and single-use filling sets.
As single-use systems are delivered as ready-to use systems, The helium integrity test occurs at the Pall site during the
the SUS supplier has an increased responsibility in the design, manufacturing of Allegro SUS. Figure 1 shows the life cycle of
manufacture and validation of SUS. That is different compared a Pall Allegro SUS with the Pall manufacturing steps in the upper
to conventional reusable stainless steel systems, where the region and the SUS deployment steps at the end-user site in the
end-user is responsible for their life cycle, from design to lower region of the figure.
maintenance, including validation, routine operation tests, etc.
When dealing with complex SUS, additional tests using a high
With SUS, the responsibility is shared between the supplier and
sensitivity pressure decay test may be required on the SUS fluid
the end-user.
transfer parts. Pall can also offer these tests on request.
To develop a suitable strategy for the assurance of integrity
of SUS, in addition to the SUS application specific requirements, Working principle of the HIT method
all the steps in the life cycle of the SUS should be considered, Pall has developed a highly sensitive integrity test system using
from its design and manufacture at the supplier to its disposal helium as a tracer gas.
by the end-user. A proper risk-assessment should be performed
to define the most appropriate risk mitigation strategy. This The tracer gas detection method, in vacuum mode, is the method
risk-based approach is recommended in the Bio-Process of choice recommended by USP <1207.2>1 on package integrity
Systems Alliance (BPSA) guide on ‘Design, Control, and leak test technologies. Helium is used as a tracer gas, due to
Monitoring of Single-Use Systems for Integrity Assurance’ its favorable properties (inertness and small atomic size), in an
(http://bpsalliance.org/technical-guides). inside-out test method, where helium leaking from the defects is
collected in the test chamber (Figure 2).
Quality by Design (QbD) principles, junction tests, visual inspection,
quality control tests and validated processes are used for all Figure 2
Pall manufacturing procedures to ensure robustness and Test chamber schematic
integrity of manufactured SUS. Additionally, Pall can perform
the helium integrity test (using Pall HIT technology) upon request
for Allegro single-use (SU) assemblies. The HIT method provides
the highest level of control of integrity for SUS incorporated
into the most critical steps of drug substance or drug product
bulk storage.

Figure 1
SUS life cycle with Pall and end-user steps

Pall Manufacturing Quality by Design

Development Validation
Component Helium High Sensitivity Routine Testing
Manufacturer Integrity Pressure Decay
Test Test (1) Test (2)

SU Allegro
Components Biocontainer Transfer Sets Packaging Irradiation Shipment
Systems and
Filling Sets

Disposal Use Installation

Post-Use Test Pre-Use Test

Point-of-Use Test of SUS

Test by SUS end-user

Operator Training

End-User Deployment
(1) and (2) are tests performed upon customer request

2
A highly sensitive mass spectrometer (MS) connected to the Applications
test chamber quantifies helium gas concentration. A leak rate
calculated from the helium concentration in the test chamber Single-use systems for the clinical and commercial production
is compared to an acceptance criteria (threshold value) to of drugs
determine whether the tested SUS assembly passes or fails uA
 septic processes in vaccines, gene and cell therapy
the test (Figure 3). applications
u Bulk storage of mAbs, vaccines, r-proteins, etc.
Figure 3
Leak rate measurement u Aseptic filling processes

Key Elements of SUS Integrity

Pall has very high standards with regards to the design (QbD)
The Pall HIT method is a non-destructive test method. The and validation of the manufacturing process for Allegro SUS.
method and acceptance criteria have been fully validated Additional key elements of the Pall approach for assurance of
to detect down to a 2 µm defect with assemblies including integrity are the HIT test and pressure decay test at the supplier
Allegro biocontainers ranging in size from 50 mL to 50 mL to as well as a SUS leak test at the end-user (Figure 4).
200 L and Allegro mixer biocontainers in sizes up to 200 L.
End-user point-of-use in-situ leak testing to confirm
For filling set assemblies the method is validated to detect down
to a 10 µm defect. that no damage occurred during shipping, handling
or installation of the single-use system
Both comply to the MALL (Maximum Allowable Leakage Should there be a need to confirm the absence of leaks
Limit defined in USP<1207>1) approach and are correlated prior to use from a risk management perspective an easy and
to microbial ingress2. reliable point-of-use leak test can demonstrate that the SUS
has not been damaged during installation. This point-of-use test
Features Benefits
at the end-user complements Pall manufacturing tests and
50 mL to 200 L Allegro biocontainer Assurance of single-use systems provides an additional level of assurance of integrity. For further
systems integrity tested down to integrity information please refer to Pall datasheet reference USD3015 -
2 µm defects
Highest patient safety and protection Palltronic® Flowstar LGR Test Instrument.
50 L to 200 L 3D LevMixer® of operators
biocontainer systems and Allegro
Magnetic mixer biocontainer Less risk of batch losses due to leakage
systems with top hat, integrity or sterility breach
tested down to 2 µm defects

Filling sets are integrity tested

down to 10 µm defects

www.pall.com 3
Figure 4
Approach for assurance of integrity of SUS

Pall Manufacturing

SUS components (standard tests)

• Allegro Central
Management System
(ACMS) SUS integrity tests at Pall (upon request) Confirm integrity
• Quality by Design • Allegro SUS, helium integrity test (HIT platform) HIT
of SUS after
• Transfer sets, high sensitivity pressure decay test System
assembly at Pall

End-User Deployment
Confirm that
SUS was not
• Visual Inspection Point-of-use SUS leak test (in-situ) Palltronic damaged
• Operator Training • Post-installation and pre-use test Flowstar LGR between Pall
Instrument manufacturing
and point-of-use

The Palltronic® Flowstar LGR test instrument enables in-situ,

post-installation point-of-use leak testing of single-use systems
up to 200 L nominal volume and provides the ability to test
filter integrity. It allows end users to test endless configurations
of single-use systems and filters with one device, without
compromising system sterility. It is more specifically designed
for use in the vaccines, biotech, and pharmaceutical applications
with a specific focus on formulation and filling operations.

References
1. United States Pharmacopiea <1207.2> General Chapter,
Package Integrity Evaluation – Sterile Products – Package
integrity leak test options

2. Pall Biotech data - Design, Control, and Monitoring of

Single-Use Systems for Integrity Assurance, BPSA, July 2017

Visit us on the Web at www.pall.com/biotech

Contact us at www.pall.com/contact

International Offices
Corporate Headquarters Pall Corporation has offices and plants throughout the world in: Argentina, Australia, Austria, Belgium, Brazil,
Port Washington, NY, USA Canada, China, France, Germany, India, Indonesia, Ireland, Italy, Japan, Korea, Malaysia, New Zealand, Norway,
Philippines, Poland, Russia, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, United
+1.800.717.7255 toll free (USA) Kingdom, and Vietnam. Distributors in all major industrial areas of the world. To locate the Pall office or distributor
+1.516.484.5400 phone nearest you, visit www.pall.com/contact.

European Headquarters The information provided in this literature was reviewed for accuracy at the time of publication. Product data
may be subject to change without notice. For current information consult your local Pall distributor or contact
Fribourg, Switzerland Pall directly.
+41 (0)26 350 53 00 phone

Asia-Pacific Headquarters
Singapore © 2019, Pall Corporation. Pall, , Allegro, HIT, LevMixer, and Palltronic are trademarks of Pall Corporation.
+65 6389 6500 phone ® indicates a trademark registered in the USA. TM indicates a common law trademark. Filtration.Separation.
Solution. is a service mark of Pall Corporation.

4 11/19, PDF, GN19.07501 USD3273a