For nearly two years Teva struggled with impurity issues for an API manufactured at a plant in China, problems that affected about 20% of the product’s production. While the drugmaker has been working for months to get on top of the problems, the FDA has yet to be convinced it has all of its problems solved, it said in a warning letter to the generics giant.
The FDA laid out its findings in a warning letter posted Tuesday for the plant in Xiaoshan, Hangzhou in Zhejiang. Teva had acknowledged receipt of the document recently in an SEC filing.
The warning letter said that between December 2014 and the September 2016 inspection, 10% of batches of an unidentified API failed the limits for an impurity. Another 10% of batches had out-of-trend (OOT) results. The plant reprocessed the rejected OOS batches but didn’t resolve the process design and control flaws that resulted in the impurity buildup, the letter said.
Teva last fall responded to the FDA that it had found the cause of the problem but the agency was unconvinced. The letter pointed out that in March the company acknowledged it had recorded more batch testing failures since the plant resumed production of the API. That, the FDA said, is a pretty good indication that the “root cause analysis and CAPA were ineffective.”
In addition, the FDA said the plant still needed to resolve problems inspectors noted with its validation sampling plan for the API.
When Teva reported in an SEC filing this month that it was the recipient of the warning letter, it said it had initiated steps to deal with the FDA concerns “as well as the underlying causes of those concerns.” It said it would provide the FDA a full response by May 1.
This is Teva’s second warning letter in the last six months. In October, the FDA cited a Teva sterile injectables plant in Hungary, noting significant sterility concerns. The agency had earlier banned the plant from shipping any more products to the United States.