Chemolee Lab Corporation Receives Warning Letter (022316) (Click Here)
Investigators from the U.S. Food and Drug Administration (FDA) inspected Chemolee Lab Corporation, located at 3820 Conflans Road, Irving, Texas from January 12 thru February 13, 2015 and found a number of CGMP violations for exceeding microbial specifications. These included:
- Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed, and failed to extend the investigation to other batches that may have been associated with the specific failure [21 CFR 211.192]. Please note that this represents a repeat Observation from September 2011.
(b)(4) Acne Control Spot Treatment lots manufactured in August and September of 2013 were rejected because they failed established microbial specifications for total microbial count: “Fail if any CFU is greater than (b)(4).” Your quality control unit did not adequately investigate these specification failures.
For lot (b)(4), three different objectionable microorganism tests failed. Specifically, you failed testing on media used for detecting Aspergillus niger (brasiliensis), Candida albicans, and Pseudomonas aeruginosa. All three tests yielded levels that were too numerous to count (TNTC). You concluded that insufficient cleaning of the transfer pump was the root cause of these failures. On August 30, 2013, you implemented a new sanitization procedure in response to these microbial testing failures.
On September 12, 2013, the (b)(4) lot manufactured after implementation of this new sanitization procedure, lot(b)(4), failed five different objectionable microorganism tests. Specifically, you failed testing on media used for detecting Aspergillus niger, Candida albicans, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. You concluded the source of this contamination “points to somewhere in the filling process.”
Your response to the initial contamination event was ineffective as contamination continued to occur. You did not extend your investigations to other potentially affected lots such as those manufactured with common raw materials or equipment. Furthermore, your response to the second contamination event (lot (b)(4)) is also deficient in that you have not provided any data to justify your conclusion that contamination is occurring “somewhere in the filling process.” You did not find the root cause of these contamination events, and thus you will not be able to prevent them from recurring.
In your response to the FDA 483, you stated that 1:10 other drug lots manufactured on the same equipment immediately before and after lots (b)(4) and (b)(4) were found to be out-of specification (OOS) for microbial testing. You also stated that you updated your (b)(4) procedure for non-conformances and your (b)(4)procedure for corrective and preventive actions to extend failure investigations to other associated batches. Your response is inadequate because you still failed to provide scientifically sound evidence to support your conclusions about contamination sources, affected lots, and corrective actions.
Comment:
The FDA found that the Company failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed, and failed to extend the investigation to other batches that may have been associated with the specific failure (21 CFR 211.192). Chemrolee also failed to identify the “root cause”. Further, since this is a “repeat Observation” from September 2011 that has not been corrected, and cited again, it is not surprising that the Company received a Warning Letter.
Our investigators also determined that your monitoring, inspecting, and repair of the RO water system was inadequate in ensuring that it was maintained in a validated state. Beyond the failure to maintain your RO system from January 8, 2014, through October 8, 2014, microbiological test results from water sampled at the RO (b)(4) were TNTC on (b)(4) occasions. Without justification, you discontinued sampling at the RO (b)(4) that yielded these results. We note that the finished product lots that you rejected in 2013 for microbial contamination included gross contamination with Pseudomonas aeruginosa, a microorganism commonly found in water.
Comment:
While Purified Water, i.e., water leaving a RO System may contain upwards of 100 CFU/mL, gross contamination of RO water with Pseudomonas aeruginosa is unacceptable and considered a “specified organism”. In addition, anytime that a specific microorganism is isolated in numbers less than a specification, but still within “gross contamination” levels (>30 or so CFU/mL), one should attempt to determine its root cause and correct the problem.
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