PUPSITPre-Use Post-Sterilization Integrity Test

Filters can be damaged during sterilisation or installation. A post-use integrity test detects failure after the fact; PUPSIT aims to detect damage before product is exposed.

A concern is filter masking: a damaged filter partially blocked by product might pass a post-use test. PUPSIT addresses that risk.

Common non-destructive tests include bubble point, diffusion or forward flow, and pressure hold. Test parameters come from the filter manufacturer's validation for the specific wetting fluid.

The test method and limits should be qualified for the filter and fluid used.

PUPSIT requires wetting and testing downstream of a sterilised filter without compromising sterility. This adds connections, valves and vents on the sterile side, each of which is a potential contamination risk.

Good design minimises sterile-side manipulations, uses closed or single-use assemblies and is qualified.

Annex 1 accepts that PUPSIT may not always be possible, for example with very small volumes, and allows alternatives where a risk assessment justifies them and compliance is achieved.

Justifications should consider filter damage likelihood, masking potential, process design and supplier data.

Post-use integrity testing remains expected. PUPSIT complements it rather than replacing it.

Failed post-use tests require investigation and batch impact assessment.

A failed PUPSIT result can arise from improper wetting, leaks in the assembly, temperature effects or real filter damage. Retesting follows defined rules, often after re-wetting, before rejecting the filter.

Record each attempt and the conclusion; repeated testing without investigation is not acceptable.

Pitfalls include adding sterile-side connections without considering contamination risk, inadequate wetting, unqualified test limits and weak documentation of retests.

Another is applying a generic justification to skip PUPSIT across all processes.

• Design the filter assembly so the sterilised filter can be integrity tested without breaking the sterile boundary downstream.
• Define how wetting fluid is introduced and removed, and how its effect on the first product volume is handled.
• Record the test instrument, its calibration status, the test parameters and the pass limit on the batch record.
• Specify what happens on a failed test: re-wet and retest limits, filter replacement and investigation triggers.

Where a manufacturer decides PUPSIT is not feasible, EU GMP Annex 1 expects a documented risk-based justification. That justification should be reviewed whenever the filter, product or process changes.

Reviewers need to see pre-use and post-use integrity results next to the batch they protect. Capturing the results as structured fields, with the operator and time attached, makes it easier to confirm that both tests passed before the batch moves to release review.

Batch disposition remains a decision for the authorised person. A complete filter record supports that decision; it does not make it.

V5 batch records, equipment and material records can capture filter identifiers, integrity test results and deviations against the batch, keeping them traceable.

V5 does not perform integrity tests or decide test acceptance. Qualified personnel and validated instruments do.

List every sterilising filtration step and record whether PUPSIT is performed or justified otherwise. Check that justifications reflect the current Annex 1 text.

Review failed tests over the past year for patterns.

Industry debate focused on whether the contamination risk of extra sterile-side manipulations outweighed the benefit of detecting rare damaged filters. Joint industry work studied filter masking and design approaches, informing current practice.

The outcome is that design quality matters: a well-engineered single-use assembly can make PUPSIT simpler and lower risk.

Pre-sterilised single-use assemblies with integrated wetting and drain bags can enable PUPSIT with fewer manipulations. Suppliers may provide integrity and sterilisation evidence for the assembly.

Qualify the assembly as part of the process and verify supplier documentation.

A pre-use bubble point test fails slightly below the limit. The operator follows the procedure to re-wet with the specified fluid and retests; the filter passes.

Investigation finds the wetting step was shortened. The procedure is clarified, the event is logged with both results, and trending is monitored.

1. Confirm the applicable requirement, product scope and decision owner.
2. Map the current method and the records already available.
3. Define terms, responsibilities, evidence and exception handling in the approved procedure.
4. Pilot the method on one representative process and challenge a difficult exception.
5. Train affected roles, approve the change and monitor whether the method works as intended.
6. Review after significant change and retain a transparent history of decisions.

Scale the formality to risk and complexity. A small operation still needs clear responsibilities and reconstructable evidence, while a multi-site operation also needs harmonised definitions, governance and comparison rules.

• Can a reviewer identify the source, owner, method and current approved version?
• Do summaries reconcile to original records and include unfavourable or missing evidence?
• Are exceptions visible, assessed and linked to the affected material, product or process?
• Are actions assigned, overdue items escalated and effectiveness reviewed?
• Have changes in product, supplier, equipment, method or regulation triggered reassessment?
• Does the record distinguish system support from the decision an authorised person made?

• Approved scope, definitions and responsibilities for PUPSIT (Pre-Use Post-Sterilisation Integrity Testing).
• Source records and identifiers that let a reviewer reconstruct the work.
• Methods, assumptions, calculations, exclusions and any data-quality limitations.
• Exceptions, investigations, decisions, approvals and resulting actions.
• Version history showing when the approach changed and why.

Records should be proportionate to the decision and usable by someone who was not present. Preserve original evidence and corrections rather than replacing it with an unexplained summary.

• Can users trace every summary value back to its source record and version?
• How are roles, permissions, signatures and corrections recorded?
• Can the workflow reflect our approved procedure without inventing a universal rule?
• What happens during an outage, and how are later entries distinguished?
• Can we test the highest-risk exception with realistic data before committing?
• Which decisions remain explicitly assigned to an authorised person?