A recent inspection revealed a concerning discrepancy between retain samples and the actual marketed products, resulting in a 483.
The retain samples for drug products repackaged in 30-count and 60-count blister cards were not representative of the final packaging of the marketed product released to consumers.
The 483 reads:
…..Reserve drug product samples are not representative of each lot or batch of drug product.
Specifically, the retain samples specific for the drug products that are repackaged in the 30-count and 60-count blister cards are not representative of the packaging operations that your facility performs and the marketed product that is released.
Your written procedure SOP …,“Retained Samples”, instructs for a visual inspection of the retain samples by utilizing the “Sample Review Check List” at time periods of … following repackaging. The “Sample Review Check List” contains your firm’s assessment of drug product tablets/capsules inside the blister bubbles, to include documentation of drift outside the bubbles and visible degradation.
However, the firm collects … each for their retain samples, which are not representative of the repackaged 30 and 60-count final drug product blister cards. Additionally, your firm has never conducted formal comparability study of the two different packaging configurations to assess if they have comparable stability performance
In 21 CFR 211.166, the phrase “designed to assess the stability” is where the ambiguity lies. The extension of this phrase is clear in the case of the 483 in spotlight, meaning retain samples have to reflect actual product in the field.
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The extended CFR Guidance reads:
(a) There shall be a written testing program designed to assess the stability characteristics of drug products. The results of such stability testing shall be used in determining appropriate storage conditions and expiration dates. The written program shall be followed and shall include:
(1) Sample size and test intervals based on statistical criteria for each attribute examined to assure valid estimates of stability;
(2) Storage conditions for samples retained for testing;
(3) Reliable, meaningful, and specific test methods;
(4) Testing of the drug product in the same container-closure system as that in which the drug product is marketed;
(5) Testing of drug products for reconstitution at the time of dispensing (as directed in the labeling) as well as after they are reconstituted.
