Chinese API and Drug Manufacturer Issued Warning Letter

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PTSM: Pharmaceutical Technology Sourcing and Management

PTSM: Pharmaceutical Technology Sourcing and Management-01-07-2015, Volume 11, Issue 1

Analytical and procedural deficiencies result in FDA warning letter for Novacyl Wuxi Pharmaceutical.


In a warning letter dated Dec. 19, 2014, FDA cited Novacyl Wuxi Pharmaceutical in Jiangsu, China, for “significant deviations” from cGMPS for the manufacture of APIs and “significant violations” of cGMPs for finished pharmaceuticals found during an inspection in October 2013. The letter notes that Novacyl Wuxi Pharmaceuctical’s response on Nov. 6, 2013 lacked sufficient corrective action.

In citing cGMP deviations for API manufacture, FDA noted the firm’s “failure to manage laboratory systems with sufficient controls to ensure conformance to established specifications and prevent omission of data.”

The FDA inspection revealed deficiencies in documentation practices, including missing raw data.  In addition, the inspection documented that the firm made changes to integration parameters for the impurities test without appropriate documentation or justification; failed to have a written procedure for manual integration despite its prevalence; failed to use separate passwords for each analyst’s access to the laboratory systems; and used uncontrolled worksheets for raw analytical data in the laboratory. In addition, FDA noted the presence of many uncontrolled chromatograms, spreadsheets, and notes of unknown origin.

“The lack of controls on method performance and inadequate controls on the integrity of the data collected raise questions as to the authenticity and reliability of your data and the quality of the APIs you produce,” the letter notes.


FDA notes that Novacyl Wuxi Pharmaceutical stated in its response, dated Nov. 6, 2013, that the firm would create a validation program for all uncontrolled computer systems, create a new standard operating procedure (SOP), and retrain analysts performing analytical tests. “However, observations found during the most recent inspection regarding the inadequacy of your HPLC system raises questions regarding your ability to implement sustainable corrective and preventive actions, as previous commitments made to the agency were not fulfilled,” FDA reports in the warning letter.

cGMP Violations for Finished Products
FDA noted that the firm did not properly document or investigate out-of-specifications (OOS) and other discrepancies; in the case of the presence of metal particles, the firm failed to determine the root cause of the contamination or explain why the step was unable to prevent the contamination.

The company also “failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity” and did not record all CGMP activities at the time these were performed.

FDA has requested that Novacyl Wuxi Pharmaceutical provide an evaluation of the extent of the deletion and destruction of records; a risk assessment regarding the potential effect on the quality of APIs and drug products; and a management strategy that includes details of its global corrective action and preventive action plan. 

Source: FDA Warning Letter to Novacyl Wuxi Pharmaceutical Co., Ltd. 12/19/14