Kyowa Hakko has received a US FDA warning letter citing GMP and data integrity issues at its amino acid production facility in Yamaguchi, Japan.

The warning letter dated August 10 2018 came following an inspection of Kyowa Hakko Bio’s Hofu facility in September 2017 by the US Food and Drug Administration (FDA).

Deviations from current good manufacturing practice (cGMP) for active pharmaceutical ingredients (API) cited by the Agency included failures in Kyowa Hakko’s quality unit, along with a lack of data control which the FDA said calls the reliability of data into question.

“Your firm’s controls over your HPLC systems are inadequate,” the letter stated. “Some HPLC systems did not have audit trail capability or audit trails enabled. In addition, unique user names and passwords were not required to perform HPLC activities. You stated that you did not create unique usernames and passwords so that operators in different (b)(4) could continue what previous operators had initiated.”

The letter contained repeat observations cited in a previous warning letter sent to the plant in 2010, along with similar issues observed at the firm’s bio-chemical Ube facility during an inspection last year. “These repeated failures at multiple sites demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.”

Business as usual
According to the firm, the Hofu plant produces amino acid for a range of biopharmaceutical purposes, including IV and nucleic acid.

“Hofu Plant uses fermentation technology using microbes, and separation and purification technology using ion exchange resin and centrifuge,” a spokesperson from Kyowa Hakko Kirin told BioProcess Insider. The manufacturing technologies were not cited in the warning letter.

The spokesperson also confirmed no quality deficiencies in its products, and at this time, has not been instructed to recall any products and/or suspend shipments.

“We are taking the warning letter as a high priority to deal with, although we anticipate no influence to the sales since it doesn’t require any product recall or shipment stop of the company.”