The US Food and Drug Administration (FDA) has posted a Warning Letter, dated July 9, 2014, to Zhejiang Jiuzhou Pharmaceutical Co, based in Taizhou, Zhejiang Province, China, for violations of good manufacturing practices (GMPs) and misbranding of products. The letter was issued as a result of the FDA's inspection of the company's active pharmaceutical ingredients (APIs) facility, Zhejiang Jiuzhou Pharmaceutical Co., Ltd., and its import/export company Zhejiang Zonebanner Jiuzhou Imp. & Exp. Co., Ltd. (i.e.,Zonebanner), both located in Taizhou, Zhejiang Province, China. The inspection was conducted October 21 to October 24, 2013, and the firm responded by correspondence on November 14, 2013 and January 14, 2014.
With respect to cGMP violations, the FDA cited Zonebanner for failing to implement an effective system of managing quality and for failing to transfer all quality or regulatory information received from the API manufacturer to its customers. The FDA said Zonebanner, purchased APIs from an outside supplier and relabeled them without the oversight of a quality unit. The agency said that 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 doing so, your firm essentially obscured the supply chain of these APIs," said the FDA in its letter.
The agency said that Zonebanner had no quality system in place for the relabeling operations. In addition, the FDA noted that in at least one instance of a lot of gabapentin shipped to the US, the retest date from the original manufacturer’s certificate of analysis (November 2013) was changed to an expiration date listed as eleven months later (October 2014) on the new certificate of analysis.
"In your response, your firm states that Zonebanner exists as a separate legal entity under Chinese law. However, the FDA considers this entity to be under your control," said the FDA in its letter. "During the inspection, your employees stated that Zonebanner is a group within Zhejiang Jiuzhou Pharmaceutical Co. Ltd. and provided organizational charts showing that Zonebanner management reports to you as CEO. Zonebanner is located at the same physical address as the inspected manufacturing facility, and the Zonebanner personnel work in the same office space. Moreover, API shipments from Zonebanner are accompanied by a letter stating that Zhejiang Zonebanner and Zhejiang Jiuzhou Pharmaceutical Co. Ltd. are in one group. Despite this close relationship, however, your management has allowed the Zonebanner group to continue to operate outside of your firm’s quality system."
With respect to Zhejiang Jiuzhou Pharmaceutical, the FDA said the firm's quality unit failed to review batch production records prior to the distribution of an API batch. "Our investigator discovered that your firm shipped finished lots without reviewing the batch records for these lots," said the FDA in its report. "Although your firm has procedures requiring the review of batch records prior to their release and distribution, on several occasions your quality unit authorized the shipment of lots prior to their release. Several of your firm’s employees were aware of this practice but took no measures to prevent it."
The FDA also cited the firm for failing to document manufacturing operations at the time that they were performed. The agency noted instances of missing data or belated data entry with respect to cleaning events as well as data falsification and record-keeping deficiencies with a quality assurance reviewer signing off for a batch release but not having performed the review.
The FDA also cited the firm for failing to adequately maintain equipment in a state appropriate for its intended use in the manufacture of APIs, noting a leak in the purified water system, which had also been cited in earlier inspections. The current inspection also found other pieces of manufacturing equipment in need of repair.
The FDA further noted that during its inspection, the company's quality unit’s personnel indicated that the unit’s workload was too large for its current staffing levels. "Our review of the significance of current findings indicates that your quality unit is not able to fully exercise its responsibilities," said the FDA in its letter. "For instance, at the time of the inspection, your chief operating officer informed our investigator that your quality unit had not yet had time to review batch records for any products manufactured that month. It is your responsibility to ensure that adequate and appropriate resources are available to the quality unit to allow it to carry out its responsibilities."