By Tanner Vandenberg, CEO, FlexPak Leak Detectors Inc.
The FDA guidance for industry on container closure systems is the document people cite and rarely read. Here is what it actually says about demonstrating integrity, and what that means for the testing you have to be able to show.
What the FDA container closure guidance covers
The container closure system FDA guidance describes what the agency expects a drug application to contain about its container closure system: a description of the system and its components, the materials of construction, and data showing the system protects the product for its shelf life.
It is written as expectations for a submission rather than as a test method. So it names the outcome, meaning the system has to be shown to maintain integrity, without prescribing which method proves it. That is why two manufacturers can satisfy the same guidance with different tests.
What a container closure system actually is
A container closure system is the sum of the parts that hold and protect the product: the container itself, the closure, and any component that contributes to the seal or the barrier. A vial, its stopper and its crimp are one system. A pouch and its heat seal are another.
The distinction that matters for testing is that integrity is a property of the assembled system, not of any one part. A stopper that passes on its own tells you nothing about the seal it forms against a particular vial finish.
How integrity gets demonstrated in practice
The guidance expects evidence. In practice that evidence comes from a physical test on the assembled system, and the method depends on the package.
- ASTM F2096, internal pressurization. Air is introduced into the package so a defect shows even when there is little or no headspace. Detects to approximately 250 microns with roughly 81% probability. A laboratory and new-material tool.
- ASTM D3078, bubble emission. Submersion under vacuum, with the leak visible and locatable. Needs gas inside the package.
- ASTM D5094, dry chamber. For liquid-filled and low-headspace formats where submersion is not practical.
Methods you will see cited in this space that FlexPak does not perform: vacuum decay (ASTM F2338), dye penetration (ASTM F1929), helium leak, and high-voltage leak detection. If your submission strategy rests on one of those, that is a different instrument.
Container closure testing
Show an auditor how the seal was verified.
FPIPA runs ASTM F2096 internal pressurization on vials, pouches and syringes with little headspace.
Container closure integrity of parenteral vials
Parenteral vials are the hardest case in this family and worth treating separately. The seal is formed between three parts, the vial finish, the elastomeric stopper and the crimped seal, and the compression that holds it is set during capping.
Two consequences for testing. First, headspace in a filled vial is small, so a method that relies on gas already inside the package is working against you and internal pressurization is usually the better fit. Second, a change to capping force changes the seal without changing anything you can see, which is why integrity testing belongs in change control and not only in initial qualification.
For the wider sterile picture, see container closure integrity testing for sterile products.
What to have ready before an audit
Three things, and the third is the one that is usually missing.
- A described system. Every component that contributes to the seal, named.
- A method with a validated setpoint. Not a vacuum level someone chose because it seemed reasonable.
- Retrievable records. The run, the unit, the batch, the date. A test you ran and cannot produce evidence for is, to an auditor, a test you did not run.
IQ, OQ and PQ qualification support covers the second and third of those on the equipment side.
Frequently asked questions
What does the FDA container closure guidance require for integrity?
It expects a submission to describe the container closure system and provide data showing it protects the product through shelf life. It names the outcome rather than prescribing a specific test method.
What is a container closure system?
The assembled set of parts that hold and protect the product, including the container, the closure and any component contributing to the seal or barrier. Integrity is a property of the assembly, not of one part.
Which test method demonstrates container closure integrity?
It depends on the package. ASTM F2096 internal pressurization suits packages with little or no headspace, D3078 bubble emission suits packages with headspace, and D5094 dry chamber suits liquid-filled formats.
Why are parenteral vials harder to test?
Filled vials have very little headspace, so methods relying on gas already inside the package are working against you, and capping force changes the seal without any visible change.
Does FlexPak perform vacuum decay or helium leak testing?
No. Vacuum decay (ASTM F2338), dye penetration (ASTM F1929), helium leak and high-voltage leak detection are not methods we perform.
About the author
Tanner Vandenberg is CEO of FlexPak Leak Detectors Inc., which builds the equipment described here at its St. Catharines, Ontario facility. Connect with Tanner on LinkedIn.