CGMP Violations Found in Zhejiang Hisun Inspection
A 3/2-3/7/15 FDA inspection at Zhejiang Hisun Pharmaceutical Co., Zhejiang Province, China, found significant deviations from current good manufacturing practice for the manufacture of active pharmaceutical ingredients (API), according to a 12/31/15 Warning Letter. Specific deviations included:
failing to prevent unauthorized access and changes to data, and to provide adequate controls to prevent manipulation and omission of data; and failing to conduct appropriate microbiological testing on API batches where microbial quality is specified.
The letter says that agency investigators discovered a lack of basic laboratory controls to prevent changes to the firm’s electronically stored data and paper records. It was found that the company relied on incomplete records to evaluate the quality of its drugs and to determine whether they conformed with established specifications and standards. Investigators also determined, the letter says, that the firm routinely re-tested samples without justification and deleted analytical data.
“We observed systematic data manipulation across your facility, including actions taken by multiple analysts, on multiple pieces of testing equipment, and for multiple drugs,” the letter says. “You are responsible for determining the causes of these deviations, for preventing recurrence, and for preventing other deviations from CGMP.”
The agency acknowledges the company’s commitment to hire a third-party consultant, set up user access restrictions, and upgrade computerized systems with audit trails. “However,” it says, “simply activating audit trail functions and instituting password controls are insufficient to correct the broad data manipulation and deletion problems observed at your facility and to prevent their recurrence. Your management is responsible for assuring that the scope and extent of the third-party audit is adequate, including a full evaluation of sophisticated electronic systems and their potential for manipulation. Your management is also responsible for fully documenting and preserving records.”
The letter also notes that some records requested during the inspection were not provided in a timely manner. The firm was placed on an Import Alert 9/9/15. If the deviations are not corrected, FDA says it may continue to refuse admission to the U.S. of items manufactured at the facility. The company was told to respond with a list of specific steps taken to correct and prevent the recurrence of deviations cited in the letter and a timetable for completion.