The FDA had inspected the Indian facility in February 2018 and received no response from the manufacturer regarding how to deal with the inspection deficiencies found. As a result, a Warning Letter was issued by the FDA. This contains a total of four critical findings.
One of these deficiencies is pharmaceutical water, used for the production of APIs. The Indian manufacturer has failed to validate its pharmaceutical water system. Thus, the manufacturer has no evidence that the water used consistently has the required quality according to USP. This means that, according to the FDA, there is no control over the water system - appropriate maintenance, sanitation and monitoring are also lacking. The limited testing of the water carried out by the company is, of course, not sufficient according to the FDA.
Another deficiency concerns batch documentation. The manufacturing data is documented in design manufacturing records, which are later transferred to another system. The manufacturing document created in this way is then signed by the manufacturing employees. The original manufacturing documents are burned! In addition, an appropriate system for investigating deviations or OOS results is missing.
The FDA also noticed the cleaning of the manufacturing equipment and the lack of approval of the cleaned equipment for production during the inspection. The cleaning specifications were posted on a wall. According to these instructions, the manufacturing equipment is only cleaned with water. The manufacturer did not have any evidence that this procedure was sufficient. During the inspection, the inspectors noticed black encrusted equipment and rust on a filtration unit and on the inner surface of a tank.
Another issue is the omission of the name and address of the API manufacturer on the Certificate of Analysis. The FDA issued an import alert for this supplier in 2017.
On the FDA website, you will find the original Warning Letter to the Indian manufacturer.