Chinese Drugmaker Hit With FDA Warning Letter

January 19, 2016

A December warning letter to China’s Zhejiang Hisun Pharmaceutical posted last week outlines the company’s “systemic data manipulation” and cGMP deficiencies uncovered during a March 2015 inspection.

The letter to Hisun — which formed a joint venture with Pfizer in 2012 to make and sell some of the drug giant’s off-patent drugs in China — identifies a trove of improper practices. These practices include incomplete and potentially altered data — such as a lack of sample analysis records — drug test results deleted from computer hard drives, a disabled audit trail and discarded chromatograms.

“Our investigators found that your firm routinely re-tested samples without justification and deleted analytical data,” the warning letter says.  “We observed systemic data manipulation across your facility, including actions taken by multiple analysts, on multiple pieces of testing equipment, and for multiple drugs.”

The warning letter highlights that during the inspection, a company analyst removed a USB thumb drive from a computer controlling a high performance liquid chromatography.  When asked to provide the drive, the analyst instead left the room. Although company management subsequently provided a drive to the FDA, “[i]t is impossible to know whether management provided the same USB thumb drive that the analyst had removed,” the warning letter says.

In addition, the inspector reviewed a company data package that included results from HPLC injections, and audits showed there were 61 injections. However, raw data only were available for 17 of the 61 injections.

The FDA requested a comprehensive investigation and risk assessment of how the deficiencies may affect the reliability of quality information for the company’s drugs.

The warning letter also cites for the company for failure to conduct appropriate microbiological testing on API batches.

Inspectors pointed to several customer complaints of out-of-specification results from 2012 to 2014 when they tested API upon receipt. Hisun attributed the OOS results to different test methods, but it never retested the affected batches, even after the FDA pointed out the deficiency, the letter says. The agency asked Hisun to conduct retroactive microbial testing for all potentially compromised batches, as well as a review of all microbial test methods.

Hisun indicated it wanted to resolve issues, and management told the agency that specific API batches “were sold to (the) Chinese market, and it planned to retest the batches to determine whether they meet specifications.”

Hisun’s troubles reflected in the warning letter gained attention last month, when the House Energy and Commerce Committee cited allegations that one of its plant workers allegedly was caught deleting a record from a quality control laboratory during an inspection. When confronted, the worker turned and ran, the committee said, noting it as an example of the need for GAO oversight of foreign facilities. 

The FDA banned the company’s products from entering the United States.

Read the warning letter here: www.fdanews.com/01-12-16-ZhejiangHisunPharma.pdf.