The FDA has been closely scrutinizing Chinese production facilities, and now two Chinese companies with ties to Western drugmakers have been called on the mat to account for problems in their manufacturing. The FDA has issued warning letters to plants operated by Shanghai Desano Chemical Pharmaceutical and Chongqing Lummy Pharmaceutical, slamming them both for manipulating testing and turning in falsified batch test results on APIs.
Shanghai Desano, which is working with GlaxoSmithKline’s ($GSK) ViiV Healthcare, was inspected in May by the FDA, which criticized the facility for conducting “unofficial” tests of drug batches that it kept out of its official record. In an email, a ViiV spokesperson said: “We have been made aware of this FDA warning letter to Desano, and are in contact with the company on this matter.”
In an update on Friday, a ViiV spokesperson said, “After Desano informed us that they had received a Warning Letter from the FDA, we have conducted an internal review of potential implications. We can confirm that we don’t expect any supply issue as a result of this for any of the ViiV Healthcare products.”
“It is important to note that there is no involvement of Desano in the supply of dolutegravir any dolutegravir-based regimens currently marketed.“
The FDA says it found 8,400 unofficial chromatographic analyses at the Desano plant performed between 2012 and 2014. The company has acknowledged that some of those tests related to out-of-spec test results.
For the FDA, "the volume of data in these auxiliary ‘Test Folders’ suggests that performing unofficial analyses is a common practice at your facility.” It pointed out that all data needs to be reviewed by the plant’s quality unit before deciding whether to release batches.
The FDA was also disturbed by finding many electronic logs of production deviations in a folder titled “GMP Anomalies” that had never been investigated.
The agency laid out a 5-part action plan it wants the company to undertake that includes a corrective action plan that describes how the company will ensure the reliability and completeness of all of the data it generates. It also wants to know what interim steps the drugmaker is taking to “protect patients,” such as notifying customers and recalling products.
Last year, ViiV announced that it had struck a deal for Desano to manufacture dolutegravir, the active ingredient in its HIV med Tivicay, so that ViiV would have a less expensive source to produce the med for China and other developing countries.
In the case of Chongqing Lummy Pharmaceutical, the FDA inspected two plants in March. The warning letter slams the drugmaker for widespread and serious data manipulation of batch analyses. It found that the company routinely retested samples without justification and deleted raw analytical data from computerized systems that did not provide the results that were needed.
In one egregious case, the FDA said on March 4, 2016, an analyst set the gas chromatography personal computer clock back to make it appear as if testing had been done in August 2015, 7 months earlier. The analyst then performed 5 injections to produce falsified results for long-term stability for a finished API lot, deleted four and reported only the results of the final injection as passing in the quality-control data package. That was the test the quality unit then relied on to determine if the lot was within specification.
It found similar problems with 18-month stability testing: analysts would stop tests before they were complete and then reset the clock and redo the test until an acceptable result was recorded. In this instance, Chongqing Lummy was conducting tests that the FDA had ordered during a 2013 inspection. Confronted with the evidence, the plant’s quality-control manager said the company “forgot” to perform stability testing and so created falsified results for each missed time point by manipulating the controlling PC clock.
Changqing was also given a step-by-step plan for investigating and dealing with problems.
Last year, Lummy Co, a unit of Chongqing Lummy Pharmaceutical, announced a licensing deal for an oncology dendritic vaccine from Research Triangle Park-based Argos Therapeutics ($ARGS). Lummy will develop the cancer immunotherapy in Greater China.