Data Integrity Failures Found at China Facility

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FDA sent a warning letter to Jilin Shulan Synthetic Pharmaceutical Co., Ltd. after an inspection found CGMP violations including a lack of data integrity.

FDA sent a warning letter, dated May 14, 2018, to Jilin Shulan Synthetic Pharmaceutical Co., Ltd. after an inspection of the company’s Shulan City, Jilin Province, China facility found several data integrity failures. The agency stated in the letter that the company had failed to document and investigate out-of-specification (OOS) results, failed to control computerized systems, and failed to keep contemporaneous records.

Specifically, batch records showed that an operator had violated a process, but the deviation was not reported or investigated. The effects of the deviation on product quality was also not investigated. “In your response, you said the operator violated your procedure for (b)(4). Your response was inadequate because you did not explain why the operator did not follow the procedure. Also, you did not explain how you will ensure all deviations are documented and critical deviations are investigated as required,” the agency stated in the letter.

Investigators also found dual sets of laboratory records. One set of records included OOS results, while the other included results within specifications. Evidence for the passing results was not provided, and investigations into the OOS results were not conducted. “In your response, you stated that the failure to investigate these deviations was due to the staff’s lack of CGMP knowledge. You provided retest results and your updated “Out-Of-Trend (OOT) Manage Procedure.” Your response was inadequate because you addressed OOT results instead of OOS results; you did not provide your investigations into the original OOT/OOS results. You also failed to identify the root causes of the OOS results,” FDA stated.

The audit trails in standalone instruments were not enabled and no other recording and monitoring mechanisms were found by investigators. Electronic data from the instruments were backed up on a portable drive that was not password protected and stored in an unlocked drawer. Operators had full system permissions with the ability to modify and delete files. “In your response, you committed to upgrading your chromatography computer systems to a software version with audit trails. Your response was inadequate because you did not provide appropriate procedures or details on your updated computer systems to demonstrate how you will restrict access or changes to your data,” the agency stated.

The company also failed to record operations at the time of their performance, according to FDA. Blank batch production records were found pre-signed by the operator. Partially completed batch records and batch records with data changes in pencil were found. “In your response, you indicated that these deficiencies were due to the lack of oversight by your quality assurance department. Your response was inadequate because you did not explain why your quality unit did not ensure contemporaneous documentation or exercise adequate oversight,” the agency stated.


FDA asked the company to provide the agency with a comprehensive investigation into its data records and recording, a detailed investigation in protocol and methodology, interviews with current and former employees to identify the scope of data inaccuracies, an assessment of data integrity deficiencies, and a retrospective evaluation of the company’s testing, manufacturing, and other data integrity deficiencies. A risk assessment of the potential effects of failures on product quality and a management strategy for corrective actions and preventive actions were also requested.

The agency placed the firm on Import Alert 66-40 on March 1, 2018. FDA stated in the letter that it may refuse admission of product manufactured at the facility if the company fails to correct the deviations.

Source: FDA