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FDA Warns Two Chinese Drugmakers for Data Integrity Violations

Posted 30 June 2016 | By Michael Mezher 

FDA Warns Two Chinese Drugmakers for Data Integrity Violations

The US Food and Drug Administration (FDA) has issued warning letters to two Chinese drugmakers over manufacturing and data integrity issues, including backdated tests and falsified records.

The two companies, Chongqing Lummy Pharmaceutical Co., Ltd. (Lummy) and Shanghai Desano Chemical Pharmaceutical Co., Ltd. (Desano), manufacture and sell drugs in China, as well as produce active pharmaceutical ingredients (APIs) for companies abroad.

Focus covered FDA's inspection report for Desano in February as part of a review of eight FDA Form 483s for Chinese manufacturers, several of which cited data integrity issues at the facilities being inspected.

Lummy Warning Letter

FDA says it uncovered "significant deviations" while inspecting two of Lummy's Chongqing facilities from 14-16 March, 2016, which caused the agency to place the company on import alert in April.

"During the inspection, FDA's investigator discovered a lack of basic laboratory controls to prevent changes to and deletions from your firm's electronically-stored data. Your firm relied on incomplete and falsified records to evaluate the quality of drugs and to determine whether your drugs conformed with established specifications and standards," FDA writes in the warning letter.

According to FDA, Lummy employees manipulated data on multiple occasions. "[The] firm re-tested samples without justification and deleted raw analytical data from computerized systems," the letter states.

In one instance, FDA said a Lummy analyst backdated a gas chromatography test for one of the company's APIs by seven months to make it appear as though the test had been done much earlier. Then, FDA says the analyst ran the test five times, deleting the first four results and using only the final test result in the API's quality control record.

According to the warning letter, when the FDA investigator asked Lummy staff about the falsified records, a quality control manager said the company "forgot" to run the some of the tests and faked the date in order to compensate.

In response to FDA's observations, Lummy stated it would upgrade the software for its gas chromatography and high performance liquid chromatography systems and write new standard operating procedures for handling analytical data. However, FDA says these measures are inadequate as the company has not shown how the measures would "correct the broad data manipulation and deletion problems observed at [the facility]."

Because FDA says Lummy's responses to the inspection observations are inadequate, the agency says it will keep the company on import alert and may refuse to approve any new or supplemental applications that list Lummy as an API maker until the company rectifies the issues.

To do so, FDA says Lummy should hire a consultant to help it complete a corrective action plan, and says the firm must conduct a comprehensive investigation and risk assessment into its data integrity issues.

Desano Warning Letter

FDA uncovered similar issues at Desano's Shanghai facility during an inspection from 4-7 May, 2015.

According to the warning letter, the company ran "unofficial" quality control tests that it stored in a separate folder from its officially documented test results.

"Our inspection found that [Desano] performed circa 8,400 of these unofficial chromatographic analyses between 2012 and 2014," which the warning letter states led the agency to believe that running such tests was a "common practice" at the facility.

Following the inspection, Desano told FDA that some of the 8,400 unofficial analyses were "related to out-of-specification investigations" and told the agency it would assess all of the results and get back to the agency by December 2015.

However, FDA says the company's response was inadequate "because it lacks a comprehensive assessment of laboratory practices and management oversight," and failed to detail the extent of the unofficial analyses or what products might have been affected.

In another instance, FDA says it discovered a folder labeled "GMP Anomalies" containing electronic records of numerous deviations. When the FDA investigator compared one random subfolder to the company's official record for the same date, the investigator discovered the "anomalies" had not been "investigated or reported in the official deviation logbook."

According to the warning letter, the deviations included out-of-limit temperature readings for critical process parameters; incomplete batch records; batch records pre-filled before manufacturing; failure to record temperature, humidity and pressure; and failure to add portions of raw materials during manufacturing.

Here, Desano pointed to "deficient procedures and operators' errors" as the cause of the deviations, and said it would review the deviations to assess whether any products' quality suffered as a result. Again, FDA says Desano's response is inadequate as the company's review was not thorough enough to "determine if undocumented deviations could be linked to product quality defects."

As such, FDA says that until Desano can address the issues cited in the warning letter, the agency may withhold approval of applications that list the company as a manufacturer, and warns the company that its products might be refused entry to the US.

Lummy Warning Letter

Desano Warning Letter

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