Warning Letter for Indian Sterile Manufacturer

Recommendation

15/16 June 2023

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In early August, the Indian manufacturer Emcure Pharmaceuticals Ltd. received a warning letter from the FDA. In this case, the background was an inadequate analysis of the causes of deviations within the scope of the sterility test. Emcure had indicated "laboratory errors" as the cause of the positive sterility control, but failed to substantiate this finding. At the same time, possible production causes were insufficiently investigated. The FDA summarized this as follows:

• The sterility tests were performed in a closed ISO Class 5 test environment with laminar airflow. This significantly reduces the likelihood of unwanted contamination during the test. However, the possible sources of contamination that could have occurred in such a system were not sufficiently analyzed.
• No contamination was detected in the negative controls.
• In addition, the environmental monitoring data did not reveal any deviations during the test.
• The investigations performed did not reveal any gaps in the aseptic procedure of the test or in the actual procedure itself, or in the material or technology used.
• At the same time, possible causes of deviations in production were not adequately investigated.

It is also interesting to note that the microorganisms detected in the sterility test were not only found in the laboratory environment (which led to the "laboratory error" analysis) but were also detected within the production areas in the previous months. Accordingly, a comprehensive analysis of the manufacturing conditions would have been necessary.  In this context, the FDA draws particular attention to the special risks of the sealing process and the "Container Closure Integrity", as deviations and recalls had already occurred in the past.

It is worth noting that the same company had already received a warning letter in 2016 in which the following issues were listed:

• inadequate aseptic practices
• inadequate sterilisation practices 
• facility design
• unreliable environmental and personnel monitoring 
• insufficient optical controls
• incomplete, inaccurate or falsified laboratory records

As a whole series of errors in the area of production were already recorded at that time, it would have made sense to investigate the aseptic nature of the production processes, the aseptic behaviour during production and the associated contamination possibilities.

Further details can be found in the latest Warning Letter and the Warning Letter from 2016.