Data Integrity Violations Found at Japanese Facility

FDA sent a warning letter, dated Aug. 10, 2018, to Kyowa Hakko Bio Co., Ltd. after an inspection of the company’s Yamaguchi, Japan facility found current good manufacturing practice (CGMP) violations. During the inspection, which occurred from Sept. 4–8, 2017, inspectors found data integrity deviations, including the manipulation of data.

The warning letter stated that the company had performed retesting or had manipulated data after obtaining out-of-specification (OOS) results. The company told the agency that data were manipulated to meet nonconforming system suitability tests (SST) for high-performance liquid chromatography (HPLC) analysis of raw materials. “You attributed the root cause to your firm’s ‘lack of awareness of the seriousness’ of CGMP deviations, and to an ‘environment where test data could be easily manipulated.’ Your investigation stated that you reanalyzed the crude sample and concluded that it met the specification. You provided no further details on the root causes and on the effect of using a system that failed SST to test your raw material,” the agency stated in the letter. FDA asked the company to provide an assessment of the company’s quality system and perform a retrospective review of all distributed lots.

Lack of data integrity control was also cited by the FDA investigators. The agency stated that controls over HPLC systems were inadequate, and unprotected Excel worksheets were used to perform calculations and statistical evaluations of production data. “These electronic files were not secured to prevent unauthorized changes and have no change history. Your firm’s lack of data control calls the reliability of your data into question,” the agency stated. FDA asked the company to provide a review of its controls and procedures and provide a detailed corrective action and preventive action plan. The agency also detailed steps the company should take to complete data integrity remediation.

Source: FDA