Takeda took a big hit to its reputation after a U.S. recall of rare disease med Natpara last year. The reason? Rubber particles that could shed into drug vials. Now, the FDA is putting Takeda on notice once again for failing to adequately investigate and address more particulate concerns at a Japanese plant.
In a warning letter published Tuesday, the FDA knocked Takeda for failing to identify the cause of black particulate found in finished dose vials at its Hikari plant, despite multiple in-house investigations.
Following a November inspection, FDA investigators also found that Takeda failed to address a malfunctioning piece of aseptic equipment––name redacted in the letter––that led to multiple in-process batches being rejected. The drugmaker launched "multiple investigations" into the malfunctioning machinery but later testing turned up the same issues, underscoring Takeda's inability to address the problem.
In a statement Wednesday, Takeda pledged to "respond to the FDA within the targeted timeframe" and said it was performing daily monitoring of its drug supply.
The concerns over particulate contamination are no laughing matter after the drugmaker launched recalls for hypoparathyroidism med Natpara in September.
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Takeda pulled the supplies on the chance that small rubber particles could shed into the drug's injectors.
The particles could come from a rubber covering, or septum, in the injector cartridge, the company said. When the septum is repeatedly punctured over the 14 days each injector is used, small rubber fragments could get into the cartridge.
The recall caused a minor uproar as patients who relied on the drug had few options. Suddenly stopping therapy raised the risk of a precipitous drop in blood calcium levels. One Natpara patient, Lindsey Cowles of Clearfield, Utah, told FiercePharma that the recalls "left many of us in a panic about our future."
A Takeda spokesperson on Thursday clarified that Natpara is not produced at the Hikari facility.
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In its warning letter, the FDA also nailed Takeda employees for a rash of cleanliness issues, including failing to sanitize their gloved hands after touching surfaces "such as curtains and computer screens."
During the FDA's inspection in November, investigators also found that employees "conducted manipulations using rapid movements, rather than slow and deliberate aseptic technique," investigators said. The FDA also discovered that employees were using sterile wipes with a "lack of traceability"––meaning investigators couldn't determine whether the specific wipes being used had been formally received into inventory.
In response to the plant's aseptic concerns, Takeda promised the FDA it would institute new training protocols for its employees, but the agency wasn't impressed with the plan.
"We acknowledge from your response that you have retrained your operators in aseptic behavior, but you did not extend this training to supervisory staff," the FDA letter read.
Editor's note: This story has been updated to include a comment from Takeda.