Case File #03 — OOS Investigation Closure

Inspection Trigger

Investigator reviewed OOS investigation file OOS-2024-0031 for an assay result on Metformin HCl Tablets 500 mg. The investigation was complete, the result was invalidated, and the batch was released. The investigator then asked who authorized the OOS conclusion and under what evidentiary standard.

Decision Failure

The firm could not produce documentation identifying who authorized the invalidation decision, what Phase I and Phase II evidence was evaluated before that determination, or what regulatory standard governed the authorization.

Regulatory Exposure

21 CFR 211.192 and FDA's 2006 OOS Guidance require that OOS investigations follow a defined two-phase process and that the disposition decision be formally authorized. The authorization decision — who evaluated what evidence and on what basis — must exist as a reconstructable record.

Decision Defense Record

An OOS authorization record documenting named decision owner, Phase I and Phase II findings evaluated, assignable cause determination, invalidation criteria met, and timestamped authorization would have produced an inspection-defensible conclusion and answered the investigator's question immediately.

The inspector pulled the OOS file. The investigation was thorough. Then they asked: "Who authorized invalidation, and what evidence supported that call?"

That question ends careers. Not because the investigation was wrong — but because the authorization logic was never captured as a formal record.

This case file gives you that record.

Section 01

What the Investigator Asked

483 Observation — OOS Authorization Failure

During inspection of the quality control laboratory, the investigator reviewed OOS investigation file OOS-2024-0031, initiated following an out-of-specification assay result for Metformin HCl Tablets 500 mg, Lot 2024-0031. The investigation file contained Phase I laboratory investigation records, Phase II full investigation documentation, analyst interview records, and retest results. The result had been invalidated and the batch released. The investigator requested documentation identifying who authorized the invalidation determination, what evidence was reviewed before that decision was made, and how assignable cause was confirmed rather than suspected. No authorization record responsive to any of these questions was produced.

Inspector's Question

"Who authorized the OOS conclusion — and what evidence was evaluated before that determination was made?"

A completed OOS investigation file confirms that an investigation occurred. It does not document an authorization decision. The investigator's question targets something different — the formal determination that the Phase I and Phase II findings supported invalidation, that assignable cause was confirmed, and that the decision owner accepted responsibility for the conclusion.

A QA signature on an investigation closure form confirms review. It does not document the authorization logic — what evidence was evaluated, how assignable cause was confirmed rather than hypothesized, and who held the authority to formally authorize the invalidation. That distinction is what generates the observation.

Section 02

Evidence Present vs. Authorization Missing

What Existed	What Was Missing
✓ Completed OOS investigation report	→ Named individual who authorized the OOS conclusion
✓ Phase I and Phase II investigation data on file	→ Formal record of what evidence was evaluated before authorization
✓ Assignable cause hypothesis documented	→ Documentation of how assignable cause was confirmed, not suspected
✓ Analyst retest results within specification	→ Documented basis for accepting retests as the basis for invalidation
✓ QA signature on investigation closure form	→ Regulatory standard applied to the authorization decision
✓ Batch disposition and release recorded in QMS	→ Timestamped authorization statement confirming decision preceded release

A completed OOS investigation confirms that a two-phase process was executed. It does not document the authorization decision. The authorization record identifies who evaluated the Phase I and Phase II findings, how assignable cause was confirmed against a defined standard, and who formally accepted responsibility for the invalidation and release determination — at the moment it was made.

Section 03The Operational Cost — Retrospective OOS authorization review required for all investigations closed in the preceding 24 months. OOS SOP revised to require formal authorization documentation at invalidation. Assignable cause confirmation standard defined and incorporated into Phase II investigation procedure.

Section 04DDR Reconstruction — The complete Decision Defense Record for this OOS authorization: named decision owner, Phase I and Phase II findings evaluated, assignable cause determination rationale, invalidation criteria confirmed, regulatory standard anchored, and timestamped authorization statement.

Section 05Authorization Model — The six required elements for OOS investigation authorization, including the assignable cause confirmation standard and the invalidation criteria framework FDA expects to see documented at the time of the decision.

Section 06Preventive Control — Mandatory authorization record at OOS conclusion, structured Phase II evaluation log, and release gate requiring formal decision documentation before disposition status is available in the QMS.

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OOS Investigation Closure — The result was explained. But who authorized that conclusion?

What the Investigator Asked

Evidence Present vs. Authorization Missing

Does your organization have authorization records that hold up under this level of scrutiny?