Zhejiang Medicine Receives FDA Warning Letter

August 17, 2016
Pharmaceutical Technology Editors

PTSM: Pharmaceutical Technology Sourcing and Management

PTSM: Pharmaceutical Technology Sourcing and Management-09-07-2016, Volume 11, Issue 9

The Chinese facility was cited for data integrity violations.

FDA sent a warning letter to Zhejiang Medicine Co. Ltd. on August 4, 2016 for violations of current good manufacturing practices (CGMP) in regards to data integrity. The violations were observed during a June 2015 inspection of the company’s Shaoxing, Zhejiang facility. 

During the June 2015 inspection, investigators found that the company had failed to include complete testing data in laboratory control records. Gas chromatography (GC) analysis for residual solvents was performed on product samples, and the results were recorded in separate folders that were not part of the official quality control records. The company did not consider these results when they evaluated the quality of the API or when batch release decisions were made. FDA stated in the warning letter that the company’s response to the citation, that they performed ‘pre-trial’ sample analysis to check system suitability not for compliance, was inadequate because “FDA considers the use of an actual sample in test, prep, or equilibration runs as a means of disguising testing into compliance, a violation of CGMP.”

FDA also said in the letter that the company failed to have sufficient controls over computer systems. Specifically, the investigator found that the GC system lacked controls to prevent the manipulation, deletion, or unauthorized access of data. Analysts shared a common login ID and password. “Your use of universal administrator privileges and a single common login/password meant that actions could not be traced to specific individuals. Additionally, because the audit trail feature on the system’s software was not configured to create a file history for all activities executed by the user during analysis, your electronic data was exposed to manipulation and/or deletion without traceability,” FDA stated in the letter.

Analysts were observed pre-dating or backdating results of API quality control results and laboratory worksheets. “Worksheets were dated five days before the tests that they purported to document were actually carried out. Our investigators also observed analysts signing and dating microbiological testing laboratory worksheets five days before the test results would be available and backdating laboratory worksheets for impurities and content testing by four days,” FDA stated.

To correct these violations, FDA recommended to the company that they complete a comprehensive investigation of their quality system in regards to data integrity. The company was advised to complete an investigation of protocol and methodologies that includes a summary of all laboratory, operations, and systems. FDA advised the company to have a third party interview current and former employees to identify root causes of data inaccuracies. An assessment of data integrity deficiencies and an evaluation of analytical testing data integrity were also recommended. FDA also detailed a strategy for corrective actions and preventive actions that the company should perform.

Source: FDA