Lack of OOS investigation leads to FDA Warning Letter

Recommendation

27/28 November 2019
Barcelona, Spain

Setting Specifications and Acceptance Criteria

This FDA warning letter issued to Chinese manufacturer of active pharmaceutical ingredients (APIs) Jilin Shulan Synthetic Pharmaceutical Co., Ltd. on 14 May, 2018 is based on an inspection that has taken place in November 2017. During this inspection, the FDA criticised in particular that there had been no proper investigation into OOS results.

The FDA inspector discovered that the company failed to record, investigate and resolve OOS results in the laboratory. He found two different datasets of overall 9 batches. One of the datasets contained OOS results while in the other dataset, all results where within specification.

The company could not justify that only the convenient results had been submitted while the OOS results hadn't. No root cause investigations had been performed for these OOS results. The quality department confessed to this during the FDA inspection. In their response after the FDA inspection, Jilin Shulan stated that the respective employees had a lack of cGMP knowledge.

They submitted the retest results as well as the SOP "Out-of-Trend (OOT) Manage Procedure" to the FDA. This answer was deemed insufficient, since the document covered OOT, but not OOS investigations. There had been no review of the OOS results.

It was also criticised during the FDA inspection that the Audit Trails of the electronic laboratory instruments (HPLC, GC, IR) had not been enabled.

Find further details in the FDA warning letter to Jilin Shulan Synthetic Pharmaceutical Co., Ltd. from 14 May, 2018.