PUPSIT Risk-Based Justification · Naga Mounika Nuguri

Document type	Risk Assessment
Topic area	Drug Product
Level	Advanced
Updated	September 2026

This is a ready-to-use risk assessment for the pre-use, post-sterilization integrity test (PUPSIT) decision: perform it, or justify a risk-based omission consistent with EU Annex 1 (2022), which sets PUPSIT as the expectation and puts the burden of proof on the sponsor who wants to skip it. Replace every <<FILL: ...>> placeholder with your own specifics and route it through your normal document control, review, and approval. A worked filled specimen follows. Verify each cited reference against the current source before you rely on it.

Document control header

Field	Entry
Document title	PUPSIT Risk-Based Justification for `<<FILL: product / process step>>`
Document number	`<<FILL: e.g. PUP-2026-02>>`
Version	`<<FILL>>`
Effective date	`<<FILL>>`
Filter / housing	`<<FILL>>`
Document owner	`<<FILL: e.g. Validation Lead>>`

1. Purpose

This assessment documents the decision to perform PUPSIT on the final sterilizing filter for <<FILL: product>>, or to omit it, based on a documented, risk-based evaluation of flaw-masking probability, the strength of the post-use test alone, and any compensating engineering controls, consistent with EU Annex 1 (2022) section 8.

2. Scope

Dimension	Decision
Filter / process step assessed	`<<FILL>>`
Batch volume typically filtered	`<<FILL>>`
Bioburden and particulate load at point of filtration	`<<FILL>>`
Out of scope	`<<FILL: e.g. prefilters, covered separately>>`

3. Responsibilities

Role	Responsibility
Validation lead	Performs the risk assessment, drafts the recommendation.
Manufacturing / engineering	Confirms feasibility and design of any PUPSIT engineering controls, or confirms constraints driving an omission request.
Quality Assurance	Approves the final decision; owns the risk acceptance if PUPSIT is omitted.

4. Flaw-masking probability assessment

Factor	Assessment	Contribution to flaw-masking risk
Batch volume filtered	`<<FILL>>`	`<<FILL: higher volume = more opportunity for a defect to be masked by accumulated product/bioburden>>`
Bioburden load prior to filtration	`<<FILL>>`	`<<FILL>>`
Particulate load prior to filtration	`<<FILL>>`	`<<FILL>>`
Filtration duration	`<<FILL>>`	`<<FILL>>`

5. Strength of the post-use test alone

Field	Entry
Post-use test method and validated sensitivity	`<<FILL>>`
Correlation study reference (retentive vs. non-retentive population)	`<<FILL>>`
Historical post-use test failure rate at this step	`<<FILL>>`

6. Compensating engineering controls (if PUPSIT is performed)

Control	Present?	Description
Redundant downstream filter protecting the line during the pre-use test	`<<FILL: Yes/No>>`	`<<FILL>>`
Sterilized test gas	`<<FILL: Yes/No>>`	`<<FILL>>`
Closed, automated test rig	`<<FILL: Yes/No>>`	`<<FILL>>`

7. Decision

Field	Entry
PUPSIT performed or omitted	`<<FILL>>`
Basis for decision	`<<FILL>>`
If omitted: residual risk statement	`<<FILL>>`
Compensating controls relied upon (if omitted)	`<<FILL: e.g. low volume, low bioburden, strong post-use test correlation>>`

8. References

EU GMP Annex 1 (2022), Manufacture of Sterile Medicinal Products, Section 8. PDA Technical Report No. 26, Sterilizing Filtration of Liquids. ASTM F838, Standard Test Method for Determining Bacterial Retention of Membrane Filters Utilized for Liquid Filtration.

Confirm the current version of each reference before issue.

9. Revision history

Version	Date	Author	Summary of change
`<<FILL: 1.0>>`	`<<FILL>>`	`<<FILL>>`	Initial issue.

10. Approvals

Role	Name	Signature	Date
Author (Validation lead)	`<<FILL>>`
Reviewer (Manufacturing/Engineering)	`<<FILL>>`
Approver (QA)	`<<FILL>>`

Filled specimen

Extract for an example gene therapy drug product fill step with a small batch volume. Company, product, and numbers are illustrative.

Factor	Assessment	Contribution to flaw-masking risk
Batch volume filtered	3 liters, small patient-scale batch	Low; small volume gives limited opportunity for bioburden or particulate to accumulate and plug a pre-existing defect
Bioburden load prior to filtration	Bioburden testing consistently below 1 CFU/mL at this step across the last 20 batches	Low
Particulate load prior to filtration	Formulated drug product, no particulate-generating upstream step immediately before this filter	Low
Filtration duration	Under 20 minutes	Low; short duration limits accumulation

Post-use test: diffusive flow, correlation study RA-FV-018 shows a clear separation between retentive and non-retentive populations with a 3x margin at the production limit; no post-use test failure recorded at this step across 20 prior batches.

Decision: PUPSIT omitted. Basis: small batch volume, consistently low bioburden and particulate load, and a strong post-use test with a well-characterized correlation and clean historical performance together support a documented conclusion that the flaw-masking mechanism has minimal opportunity to operate at this scale. Residual risk accepted by QA, with the assessment scheduled for review if batch volume, bioburden control, or the filter/housing configuration changes.

Common inspection findings this justification prevents

PUPSIT omitted with no documented risk assessment on file at all.
A risk assessment that asserts low flaw-masking risk without batch volume, bioburden, or particulate data to support it.
The post-use test’s own strength never evaluated as part of the justification.
A justification written once and never revisited after a scale, formulation, or process change that could change the risk.
PUPSIT performed without engineering controls addressing its own contamination risk, with no documentation that this trade-off was considered.

How to adapt this justification

Set your document number, filter, and process step in the header.
Populate section 4 with real batch volume, bioburden, and particulate data, not assumed values.
If PUPSIT is performed, document the engineering controls in section 6 that manage its own contamination risk.
State the decision and its basis in section 7 in language a reviewer can evaluate independently, not a bare conclusion.
Set a trigger for reassessment (scale change, formulation change, process change) so this justification does not go stale silently.