FDA Warns Drugmakers in Asia Over Poor Data Integrity, Lack of Process Validation
The US Food and Drug Administration (FDA) warned two drug manufacturing facilities in Japan and China over failures to ensure data integrity and validate processes, among other violations.The warning letters issued to both facilities were made public on Tuesday, following FDA site inspections that revealed significant violations of good manufacturing practices (GMP) for finished pharmaceuticals and for active pharmaceutical ingredients (APIs).
The firms’ drug products are considered adulterated as a result of the cited GMP violations.
Kyowa Hakko Bio
The FDA investigator who conducted the September 2017 inspection at Kyowa Hakko Bio’s manufacturing facility in Yamaguchi, Japan found violations relating to the manipulation of out-of-specification data to obtain the desired testing results.
The firm attributed the root cause to its “lack of awareness of the seriousness” of the cited nonconformities and to an “environment where test data could be easily manipulated,” according to the warning letter. This violation was observed at the firm’s facility in Ube, Japan, as well.
“These repeated failures at multiple sites demonstrate that executive management oversight and control over the manufacture of drugs is inadequate,” said Towanda Terrell, an FDA compliance officer. According to Terrell, the firm should “immediately and comprehensively assess” its “global manufacturing operations to ensure that systems and processes, and ultimately, the products manufactured, conform to FDA requirements.”
The firm’s controls over its high-performance liquid chromatography systems (HPLC) were also found to be inadequate at the time of FDA’s visit due to a lack of audit trail capabilities and unique usernames and passwords for performing HPLC activities.
In its annual product reviews, the firm “used unprotected Excel worksheets to perform calculations and statistical evaluations of production data, such as standard deviation and process capability,” Terrell added. “These electronic files were not secured to prevent unauthorized changes, and have no change history.”
Other data integrity remediation steps the warning letter calls for include conducting interviews with current and former employees and a current risk assessment of the potential quality effects.
Hangzhou Karic Commodities
China-based Hangzhou Karic Commodities has been placed on import alert pending adequate resolution of the cited GMP violations, including a failure to validate the processes the firm had been using for manufacturing drug products at the time of the March 2018 FDA site inspection.
The firm “did not conduct process performance qualification studies” and it lacked an “ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality,” said FDA compliance officer Carrie Ann Plucinski.
The firm was also cited over the release of several over-the-counter drug products that had not been subject to adequate testing for active ingredients’ identity and strength. “Without this testing, you cannot determine if your drug products conform to specifications,” Plucinski said.
Other GMP violations relate to failures in testing incoming raw materials and conducting thorough investigations into incorrect packaging material.
Kyowa Hakko Bio Co., Ltd. 8/10/18
Hangzhou Karic Commodities Co., Ltd. 7/31/18