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Record Plug-and-play starting point Sterility & Microbiology

Record: Sterility Test Positive Investigation and Invalidation Decision

A plug-and-play investigation record for a sterility test positive: isolate identification, environmental and control review, isolate comparison, adjudication against the four USP <71> invalidation criteria, and batch disposition, with a filled specimen.

Document type: Record

Read and copy the template below into your own quality system. It is a generic starting point for your own internal use, provided as is, with no warranty; see the Terms and License. Adopting it does not by itself create compliance.

This is a ready-to-use investigation record for a sterility test positive. It structures the evidence and the adjudication so an invalidation decision is defensible and a batch is never retested into compliance. Replace every <<FILL: ...>> placeholder, keep one record per positive event, and route it through QA. The default outcome of a positive is batch rejection; invalidation is the exception, allowed only when a USP <71> criterion is unequivocally met. A field guide and a filled specimen follow. The compendial chapter is copyrighted; the four criteria below are described in original wording, and you must read the current chapter. This is general guidance to adapt and verify, not legal or regulatory advice. This record pairs with the SOP: Sterility Testing (USP <71>).

Event header

FieldEntry
Record ID<<FILL: e.g. SPI-2026-0007>>
Product / batch<<FILL>>
Test / worksheet reference<<FILL>>
Day of growth<<FILL: incubation day observed>>
Medium / vessel<<FILL: FTM or SCDM, vessel ID>>
Analyst / date observed<<FILL>>
Batch statusQuarantined (confirm)

1. Immediate actions

  1. Batch quarantined and on hold: <<FILL: Yes / ref>>.
  2. Turbid vessel preserved, not discarded: <<FILL: Yes>>.
  3. Isolate submitted for identification: <<FILL: submission ref>>.
  4. QA and SME notified same day: <<FILL: date / time>>.

2. Organism identification

FieldEntry
Method (MALDI-TOF, 16S/ITS, phenotypic)<<FILL>>
Genus / species<<FILL>>
Organism character (skin commensal, waterborne Gram-negative, mold, spore-former)<<FILL>>
Matches personnel/environment library?<<FILL: Yes/No, library ref>>
Matches a product/component/manufacturing isolate?<<FILL: Yes/No, ref>>

The identity is the single most informative piece of evidence. A skin commensal points toward handling; a waterborne Gram-negative or an environmental mold needs more work before any conclusion.

3. Session evidence review

EvidenceResultWithin limits / clean?
Viable air, settle, surface EM<<FILL>><<FILL>>
Personnel glove / gown monitoring<<FILL>><<FILL>>
Isolator / cabinet performance, particle counts, alarms<<FILL>><<FILL>>
Media-only negative controls<<FILL>><<FILL>>
Method negative control (rinse + membrane)<<FILL>><<FILL>>
Media growth promotion for the lot<<FILL>><<FILL>>
Technique / procedure / interventions review<<FILL>><<FILL>>

4. Adjudication against the USP <71> invalidation criteria

Mark each criterion met only if the evidence above supports it unequivocally.

#Criterion (paraphrased)Met?Evidence
1Monitoring shows the sterility testing facility environment was out of control during the test<<FILL: Yes/No>><<FILL>>
2Review reveals a fault in how the test procedure was carried out<<FILL: Yes/No>><<FILL>>
3The negative controls show microbial growth<<FILL: Yes/No>><<FILL>>
4The isolate identification attributes the growth without ambiguity to a materials or technique fault of the test itself<<FILL: Yes/No>><<FILL>>

Decision rule: invalidate only if at least one criterion is unequivocally met. If none is met, the result stands and the batch is rejected. You cannot retest into compliance (the Barr principle, United States v. Barr Laboratories, 1993).

5. Decision

FieldEntry
Outcome<<FILL: INVALIDATE (criterion met) / CONFIRM FAILURE (reject)>>
Basis<<FILL: which criterion, or why none met>>
If invalidated: retest authorized (same number of units)<<FILL: ref>>
Retest result<<FILL: no growth / growth>>
Batch disposition<<FILL: release subject to conclusion / reject>>
Scope assessment (other lots, process, water, CCS)<<FILL>>
CAPA reference<<FILL>>
QA adjudication board / date<<FILL: members, date>>
QA approval<<FILL: name, signature, date>>

Field guide

  • Do not begin from “the first one was probably contamination.” Begin from batch failure and let the four criteria pull you off it only with unequivocal evidence.
  • Speciate the isolate; a Gram stain alone is not identification.
  • Missing negative controls or missing growth promotion for the run usually forces a confirmed failure, because you cannot rule the lab in or out.
  • An invalidation retest uses the same number of units as the original test, not fewer.

Filled specimen

Two contrasting outcomes on the same product.

Case A, invalidated. 2 mL injectable, day 6, one SCDM vessel turbid. ID: Staphylococcus epidermidis (coagulase-negative skin staph). EM: the analyst’s right-hand glove-print plate at action level with S. epidermidis; isolator background and other plates clean; negative controls clear; growth promotion and procedure records clean. The isolate matches the analyst’s glove.

CriterionMet?Evidence
1 Environment out of controlNoIsolator and background within limits
2 Procedural faultNoRecords clean
3 Negative controls grewNoClear
4 ID attributes to test techniqueYesPersonnel glove excursion with matching S. epidermidis

Decision: invalidate (criterion 4). Retest with the same number of units read clean. Batch released subject to the full investigation, with a CAPA on aseptic technique and gowning.

Case B, confirmed failure. Same product, day 6, one turbid SCDM vessel. ID: Ralstonia pickettii (a waterborne Gram-negative). EM clean, negative controls clear, technique sound, growth promotion clean. No lab fault to point to, and the organism is a plausible water-system contaminant.

CriterionMet?Evidence
1-4NoNo environmental, procedural, control, or ID-based fault of the test

Decision: confirm failure, reject the batch. Scope assessment opens on the water system and the process, and other lots on the same line are assessed. No retest to a pass is attempted.

The two cases share almost everything except the organism identity and the personnel evidence, and that is exactly where the decision turns.

Common inspection findings this record prevents

  • Invalidating on “probably technique” without an identified organism or environmental and control evidence.
  • Retesting to a pass with no valid, documented laboratory cause.
  • Identifying the isolate only to Gram stain.
  • No scope assessment after a confirmed failure.

How to adapt this record

  1. Point the immediate-actions and disposition sections to your deviation, CAPA, and batch-disposition SOPs.
  2. Name your isolate library and identification methods.
  3. Define your QA adjudication board membership in advance, not during the event.
  4. Confirm the four criteria wording against the current USP <71> before issue.
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