China-Based API Manufacturer Warned about CGMP and Misbranding Infractions

FDA has issued a warning letter to a China-based API manufacturer and its import/export company for multiple CGMP violations and misbranded products. The infractions were noted during an Oct. 21-24, 2013 inspection at API manufacturer Zhejiang Jiuzhou Pharmaceutical Co., Ltd., and its import/export company Zhejiang Zonebanner Jiuzhou Imp. & Exp. Co., Ltd., both based in Zhejiang Province.

The FDA investigator observed a failure by Zhejiang Zonebanner Jiuzhou Imp. & Exp. Co “to implement an effective system of managing quality and failure to transfer all quality or regulatory information received from the API manufacturer to your customers,” according to the warning letter.

The trading company, Zonebanner, purchased APIs from an outside supplier and relabeled them without the oversight of a quality unit, FDA reports. The information from the original certificate of analysis, generated by the actual manufacturer, was transferred to a new certificate of analysis on Zhejiang Jiuzhou Pharmaceutical Co. letterhead with no information about the original manufacturer or analytical laboratory performing the analyses. In addition, a new label identifying Zhejiang Jiuzhou Pharmaceutical Co. as the manufacturer was added to drums. In taking these actions, the firm “essentially obscured the supply chain of these APIs,” reports FDA.

Zonebanner had no quality system in place for the relabeling operations. In at least one instance of a lot of gabapentin shipped to the United States, the retest date from the original manufacturer’s certificate of analysis (November 2013) was changed to an expiration date listed as 11 months later (October 2014) on the new certificate of analysis.

Although the companies argued that Zonebanner exists as a separate legal entity under Chinese law, FDA considers this entity to be under control of Zhejiang Jiuzhou Pharmaceutical Co.

Zhejiang Jiuzhou Pharmaceutical was cited for three violations including failure of the quality unit to review batch production records prior to distribution of an API batch. FDA reported that the firm shipped finished lots without reviewing the batch records for these lots. Although the firm had procedures requiring the review of batch records prior to their release and distribution, on several occasions the quality unit authorized the shipment of lots prior to their release. Several employees were aware of this practice but took no measures to prevent it, FDA reports.

The company also was cited for failure to document manufacturing operations at the time they are performed. FDA found missing entries in a use, cleaning, and maintenance logbook for the days immediately prior to the inspection. Company operators stated that lines were left blank to later add information about cleaning events that may have occurred during a previous shift. During the inspection, FDA found other similar instances of missing data or belated data entry in manufacturing records, practices that are not consistent with CGMP, FDA reports. Operators acknowledged that there is no system in place to report these lapses in the documentation system; documentation errors of this type did not require deviation investigations or notification to the quality unit.

The investigation also revealed that an employee admitted to falsifying a batch record, indicating that a review was performed when it had not been conducted.

In addition, the company was cited for “failure to adequately maintain equipment in a state appropriate for its intended use in the manufacture of APIs,” FDA reported.

The FDA investigator noted a leak in the purified water (PW) system during the October 2013 inspection; similar findings of leaks in the same PW system were noted in previous inspections. FDA also found other pieces of manufacturing equipment in need of repair and indicated that the agency would review the effectiveness of the company’s revised preventive maintenance program during a future inspection. 

FDA also recommended that the company hire a third-party auditor with experience in detecting data integrity problems to assist the company in evaluating overall compliance with CGMP. In addition, FDA commented that the company’s quality unit is not able to fully exercise its responsibilities.

Source: FDA