21 CFR 211.192 - Production Record Review - Investigation of Discrepancies and Failures

What it says

Any unexplained discrepancy or failure of a batch to meet its specifications must be thoroughly investigated, whether or not the batch has already been distributed. The investigation must extend to other batches of the same drug product, and to other products, that may have been associated with the specific failure or discrepancy. A written record of the investigation must be made and must include the conclusions and follow-up.

Paraphrased for plain-language clarity. Always verify against the current published regulation text.

What it means in practice

• Every deviation, OOS result, complaint or unexpected event that could indicate a quality problem triggers an investigation obligation, not just events that are formally labeled a deviation.
• The investigation must identify a root cause, not simply document that the discrepancy occurred. Describing what happened is not the same as explaining why the system allowed it to happen.
• Scope extension is not optional. The investigation must explicitly consider whether other batches, other products, or other sites could be affected by the same root cause, and document that conclusion even when the answer is no.

What FDA inspectors look for

• Whether the stated root cause is a genuine systemic explanation or a restatement of the symptom (for example, 'human error' or 'operator did not follow procedure' with no further explanation of why).
• Whether the investigation record shows evidence the scope extension question was actually asked and answered, not just assumed.
• Whether corrective actions trace logically back to the stated root cause, rather than being generic actions like retraining applied regardless of what the investigation actually found.
• Timeliness: whether the investigation began promptly after the discrepancy was identified, rather than being backfilled once required for another purpose such as a batch release decision.

Related regulations