Sampling in the Focus of the FDA

Annex 8 on Sampling of Starting and Packaging Materials of the EU GMP guidelines states: "Sampling is an important operation in which only a small fraction of a batch is taken." The Code of Federal Regulations (CFR) also places great importance to sampling. This was recently confirmed by the FDA in a warning letter. What did the FDA criticise?

In more than twenty cases, mammalian hair was found in the stopper region of vials at the facility of a drug manufacturer. An investigation showed that the main source of contamination came from the stoppers. The FDA now criticises the company for relying inappropriately on pre-shipment/tailgate samples. The company agreed to change its supplier qualification program procedures, and did introduce a special test plan for one supplier, as well as an expanded plan for the other stopper suppliers. But that was not enough for the FDA.

As is usually the case, the FDA expects "documented evidence." Consequently, the FDA wanted to see the amended supplier qualification program and the specific test plan, as well as supporting data as part of the CAPA measures. Furthermore, an increase in the sample size for one stopper supplier was initiated too late, and the FDA stated that this should also have been applied to the other suppliers. Moreover, no tightening of the ANSI test level was carried out, according to the FDA.

The FDA also explicitly refers to a question and answer document on the subject of sampling.

Conclusion: Sampling is an important GMP element for the FDA. Deficiencies related to sampling are subject to CAPA. Higher sampling numbers and a more stringent testing level should also be considered if necessary.

As usual, the entire warning letter is available on the FDA website.