The US Food and Drug Administration (FDA) has sent warning letters to two Chinese active pharmaceutical ingredient (API) makers over data integrity and good manufacturing practice (GMP) violations.
In recent years, FDA has increased its level of oversight of overseas manufacturers, which has led to a greater number of warning letters being issued to such companies.
So far in 2016, FDA's Office of Manufacturing Quality has issued 25 warning letters, 11 of which were issued to Chinese manufacturers, and seven to manufacturers in India.
The most recent warning letter was issued to Cheng Fong Chemical Co. Ltd. following a five-day inspection in April 2016 that found the company failed to appropriately maintain its facilities and investigate reports of foreign particles in finished batches.
"Our investigator observed corrosion, pitting, dirt, and leaks, on and around your drug manufacturing equipment," FDA writes.
Additionally, FDA says its investigator saw "filth, insects, wet layers of [redacted] unidentified materials on the floors, and foul odors in the cold rooms used to store raw materials and intermediates used in the manufacture of your finished API."
According to FDA, Cheng Fong officials told investigators "that the rooms had never been cleaned."
FDA also says that Cheng Fong failed to adequately investigate complaints about foreign particles in its finished products.
In one case, FDA says the company received a complaint about black particles in a specific batch of its API. However, rather than testing samples from the same batch, the company tested a different batch of API. While the test found the batch contained foreign material, FDA says the company did not identify what the foreign material was and did not extend the investigation to other batches that were likely to be affected.
The other warning letter was issued to Hebei Yuxing Bio-Engineering Co. Ltd. after an August 2015 inspection turned up evidence that the company was keeping incomplete documentation and did not adequately investigate instances of microbial contamination.
According to FDA, Hebei Yuxing ran quality control tests on batches of its products without documenting the results.
"Our investigator found the results of 2,404 high performance liquid chromatography (HPLC) injections in a folder titled 'Experimental' on instrument SZG-002-0061," FDA writes. However, when confronted about the experimental tests, FDA said Hebei Yuxing management "provided different explanations in an attempt to justify the practice, including 'fear' that the sample results would not pass."
In another instance, FDA says the company submitted two different chromatograms that corresponded to the same date, time, batch and instrument. "Both versions of these documents cannot represent the actual assay analysis conducted," FDA says.
FDA also said it found 67 instances in 2015 where Hebei Yuxing documented cases of microbial contamination that were not adequately investigated. Specifically, FDA says that while the company narrowed down four potential causes, it did not identify the root cause, or causes, of the contamination or take appropriate actions to correct them.
As a result, FDA says Hebei Yuxing must conduct a comprehensive investigation and risk assessment relating to its data integrity issues, and recommends the company hire a consultant to help it implement a corrective and preventative action plan.
Hebei Yuxing Warning Letter
Cheng Fong Warning Letter