The agency inspected the plant from May 15 to May 24, 2017, and observed that staffers at the plant were basically gaming the quality control system.
Earlier this month, the U.S. Food and Drug Administration (FDA) issued a warning letter to Fresenius Kabi AG of Germany for its plant in India.
Fresenius Kabi AG is the unit of Fresenius SE that operates more than 25 manufacturing facilities worldwide.
The manufacturing plant cited in the warning letter is Fresenius Kabi Oncology Ltd at D-35, Industrial Area, Kalyani, Nadia, West Bengal, India. The agency inspected the plant from May 15 to May 24, 2017, and observed that staffers at the plant were basically gaming the quality control system. When their drug-quality tests showed there was a problem, they stopped the tests, claiming they were the result of human or machine errors. The FDA cited 248 such events at the facility.
The letter cites an example, when an out-of-specification (OOS) impurity was observed in a batch of active pharmaceutical ingredients (API), they stated that “over-sonication might have increased the temperature of the water bath and caused degradation of the sample solution.”
The letter goes on to say, “However, your investigation lacked evidence to support this possible root cause. Instead, your investigation found that the analyst only briefly sonicated the solution … at temperature. In addition, degradation studies conducted as part of high performance liquid chromatography (HPLC) validation showed that heat degradation was minimal even after (b)(4) at extremely high … temperatures.”
Although the agency noted that the company has acknowledged the need to correct the problem, their response was inadequate.
“It is essential that you initiate an immediate and comprehensive assessment of your company’s global manufacturing operations to ensure that systems and processes, and ultimately, the products manufactured, conform to FDA requirements at all your sites,” the letter states.
The FDA provided a four-step plan for resolving the quality issues, including the company undertake a retrospective review of all invalidated results related to the U.S. market, assess the company’s overall system for investigating OOS results, evaluate all cases where a chromatographic run was interrupted or aborted, and provide an updated laboratory investigation procedure.
The letter also referred to a previous warning letter that cited similar problems, saying that “these repeated failures demonstrate that your facility’s oversight and control over the manufacture of drugs is inadequate.”
If the company doesn’t comply, the FDA could refuse drugs with those ingredients manufactured at that facility from entering the U.S. market.
The specific API were redacted in the letter, but Fresenius manufactures APIs used in many types of chemotherapeutics.
Fresenius SE is Europe’s largest publicly traded healthcare provider. The company made two big acquisitions in 2017, buying Illinois-based generic pharmaceutical company Akorn in April for $4.3 billion, and also in April, paid Merck KGaA $184.7 million, plus licensing fees and up to 500 million euros in milestone payments for the company’s biosimilars portfolio.
