21 CFR 211.170 - Reserve Samples

What it says

An appropriately identified reserve sample representative of each lot of active ingredient and, where applicable, each lot of drug product must be retained, in the same container-closure system as marketed where applicable, for a defined period after the batch's expiration date, and visually examined at least annually for evidence of deterioration.

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

What it means in practice

• Reserve samples exist specifically to support future investigation - if a complaint or stability signal emerges after distribution, the physical sample of that exact batch must still be available to test.
• Retention in the actual marketed container-closure system, not a separate storage vessel, is expected where applicable, since the sample must represent real-world storage conditions for the product.
• The annual visual examination requirement is a distinct, standing obligation, not something triggered only when a specific concern about a batch arises.

What FDA inspectors look for

• Whether reserve samples are actually retained for the full required period and remain identifiable and traceable to their specific batch.
• Whether the annual visual examination is genuinely performed and documented, with any observed deterioration triggering follow-up investigation.
• Whether reserve sample quantities retained are sufficient to support the testing that might realistically be needed for a future investigation.

Related regulations