Container-closure integrity testing system
CCI testing · CCIT · Leak testing · Vacuum decay
The testers and methods that show sealed containers do not leak: by sampling or every unit, as the closure type requires, with methods validated to a known detection limit.
What this page does not claim
An equipment family page teaches how a kind of equipment works and how it is assured. It is not a qualification of any site’s equipment, sets no universal limits, and was checked by SPEQ against the sources it lists, not by an independent engineer.
WHAT IT DOES
A sterile product stays sterile only while its container stays closed. Annex 1 asks that final containers be "closed by appropriately validated methods" (8.21); that for fusion-sealed containers the parameters affecting seal integrity be controlled and monitored; and that other containers be sampled and tested by validated methods with a scientifically justified sampling plan (8.22, 8.23).
It is explicit that "visual inspection is not considered as an acceptable integrity test method" (Annex 1, 8.22). Deterministic methods such as vacuum decay, high-voltage leak detection and headspace analysis detect a leak path physically; dye and microbial ingress tests are probabilistic.
Where it sits: In process for fusion-sealed units, at release on samples, during stability across shelf life, and in container-closure validation including shipping.
WHERE YOU FIND IT
- Glass ampoules, BFS and FFS units, and bags closed by fusion
- Stoppered and crimped vials and syringes, by sampling
- Containers sealed under vacuum, before release and during shelf life (Annex 1, 8.24)
In the reference facility: Aseptic filling & isolator line, QC analytical laboratory, Packaging, labelling & serialisation
Not covered on this page: Package integrity of secondary packaging; Sterile barrier systems for components, covered in sterilisation packaging.
MAJOR COMPONENTS
- Test head or chamber. Holds the container for vacuum, pressure or electrical testing.
- Detector. Pressure transducer, high-voltage electrodes, laser headspace analyser or tracer gas sensor.
- Positive controls. Containers with known, calibrated defects that show the method detects at its claimed limit.
- Data system. Records results per unit with the method and settings used.
Connects to: Filling and sealing line; Visual inspection; Quality control laboratory; Stability programme; Transport qualification.
INSTRUMENTS AND WHAT THEY MEASURE
- Container-closure integrity tester. Leak paths in sealed containers by a validated method with a shown detection limit. Watch for: method detection limit not shown with positive controls.
- Pressure transmitter (gauge or absolute). Vacuum or pressure decay in the test chamber. Watch for: gauge and absolute values compared directly.
PARAMETERS
SETPOINT · MEASURED · LIMIT · ATTRIBUTE- Container leak result (limit, pass / fail or leak rate or equivalent orifice size). Against the method’s validated detection limit and the site’s acceptance criterion for the product and closure.
- Chamber or vessel pressure (measured, bar a or bar g or kPa). Test vacuum or pressure and decay over a defined time, for decay methods.
SPEQ publishes no universal alarm or acceptance values: they depend on the process, the product and the site’s own qualification.
CONTROLS, ALARMS AND INTERLOCKS
- Control loop: Seal parameter control. For fusion-sealed containers, controls the parameters that affect seal integrity during operation (Annex 1, 8.22).
- Interlock: In-line reject. Removes units that fail an in-line integrity test.
- Procedure: Sampling plan. Scientifically justified, based on supplier management, component specifications and process knowledge (Annex 1, 8.23).
- Procedure: Vacuum maintenance check. Vacuum-sealed containers tested after a predetermined period before release and during shelf life (Annex 1, 8.24).
An alarm asks for a response; an interlock stops an action; a safety function protects people and has its own risk basis.
HOW IT FAILS
- Method not sensitive enough. Leaks below the detection limit pass.
- Stopper or crimp defect from the line. Leak paths in a fraction of units that sampling may miss.
- Integrity lost in transport. Decompression or extreme temperatures open a seal; Annex 1 asks validation to consider shipping (8.25).
- Destructive method used where non-destructive is needed. Tested units cannot be released, so sample sizes shrink.
ASSURANCE ACROSS THE LIFECYCLE
EXAMPLES, NOT A MANDATORY LIST- Container-closure validation. Method selection and validation with positive controls; Worst-case components and process settings; Transport and shipping conditions (Annex 1, 8.25).
- Routine. In-process or release testing to the sampling plan; Seal parameter records for fusion-sealed units.
- Shelf life. Integrity in the stability programme; Vacuum maintenance for vacuum-sealed containers (Annex 1, 8.24).
WHAT THIS DOES NOT PROVE
- A unit that passed visual inspection is not shown to be integral. Instead: A validated integrity test (Annex 1, 8.22).
- A pass by a method does not prove there is no leak smaller than its detection limit. Instead: The method’s validated detection limit against the product’s maximum allowable leakage.
- Integrity at release does not prove integrity after shipping and storage. Instead: Transport validation and stability integrity results (Annex 1, 8.25).
SOURCES
2 CITED- EU GMP Annex 1: Manufacture of Sterile Medicinal Products — European Commission (EudraLex Volume 4), 2022 revision, in operation 25 August 2023. EU / EEA; revised jointly with the PIC/S Committee; in force. Supports: Validated closure (8.21); fusion-sealed containers and visual inspection is not an integrity test (8.22); sampling of other containers (8.23); vacuum-sealed containers (8.24); transport (8.25).
- EU GMP Annex 15: Qualification and Validation — European Commission (EudraLex Volume 4), 2015. EU / EEA; in force. Supports: Method and process validation approach.
HOW THIS PAGE WAS CHECKED
Researched and checked against the sources above by SPEQ (Claude) on 2026-10-21. It has not been reviewed by an independent engineer. It teaches how this kind of equipment works and is assured; it does not say any site, asset or process is qualified, validated or compliant.
- The sampling extent Annex 1 sets for small-volume fusion-sealed units is not stated: the text extracted for 8.22 was incomplete.
- USP <1207> is not yet cited; it was not checked here.
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