FDA Cites Apotex Pharmachem India for Data-Integrity Issues

The US Food and Drug Administration has posted a Warning Letter dated, June 16, 2014, for Apotex Pharmachem India based on the agency’s inspection from January 27 through January 31, 2014 of the company’s pharmaceutical manufacturing facility in Bangalore, India.  The agency cited the company for cGMP violations for the manufacture of active pharmaceutical ingredients (APIs) and said the company’s response dated  February 20, 2014 lacked sufficient corrective actions. It also acknowledged receipt of the firm’s additional correspondence dated April 4, 2014, and May 27, 2014. 

FDA cited several data-integrity issues related at the facility. Among the observations cited was that the firm lacked accurate raw laboratory data records for API batches shipped by the company. It said that the inspection revealed that batch samples were retested until acceptable results were obtained. FDA also said the quality control (QC) laboratory failed to include complete data on QC testing sheets, citing that failing or otherwise atypical results were not included in the official laboratory control records, not reported, and not investigated. It noted specific examples with regard to gas chromatography, high-performance liquid chromatography, and Karl Fischer electronic records.

In its letter, FDA said that “according to laboratory analysts interviewed during the inspection, the common practice was to complete the analysis and to record the sample preparation data only if the results were acceptable. If the results obtained were atypical, a fresh sample was to be prepared and analyzed.The original sample testing was not recorded.” FDA said that in its response to these findings, the company did not expand its investigation to discover the full scope of variances from established procedures in recording and maintaining laboratory records. FDA added that the company’s failure to create and maintain accurate documentation is a repeat observation reported during;inspections made in 2006 and 2010.

FDA also cited the firm for failure to investigate and document out-of-specification (OOS) results for testing that occurred in August 2013. The agency cited the firm for failing to prevent the practices of product sample retesting without investigation and rewriting and/or omission of original cGMP records without implementation of controls to prevent data manipulation. FDA said that the firm acknowledged deficiencies regarding data integrity observed during this inspection, but that the company’s evaluation that there was not effect on product quality was based on “unreliable and incomplete data, as undesired records appear to be excluded,” citing an example as failing to include all the batches tested. FDA is requesting that the company provide documentation of all corrective actions taken to address these failures to initiate investigations as required by the company’s procedures and to determine root cause(s) of OOS results. The failure to perform adequate investigations is a repeat observation reported during inspections made in 2006 and 2010 inspections.

FDA also cited the company for failure to record activities at the time they are performed, citing that finished product reports review data worksheet for critical laboratory information days after the actual testing was performed. FDA said that it remained concerned about the capability and credibility of the company’s quality control laboratory. FDA also noted that its inspection showed that the company selectively omitted cGMP records directly related to the testing and manufacturing of the company’s products. It also cited the company for failure to include adequate documentation during complaint investigation.            


Source: FDA

Leave a Reply

Your email address will not be published. Required fields are marked *