3-5 November 2020
Hürth near Cologne, Germany
The considered period from 2012 until the first quarter of 2014 pertains to both companies in and outside of the United States. None of the 19 mentioned warning letters is solely due to deficiencies regarding equipment. However, the big picture shows the lack of understanding of FDA requirements relative to used production equipment. In almost every case there are references to violations against requirements defined in 21 CFR 211.67 (equipment cleaning and maintenance), such as the absence of a maintenance system or a maintenance system that doesn't fulfill the requirements. In one case scratches and rust in production boilers were found. In another case the authority found obvious defects with regard to the condition of the equipment, and in addition objected to the complete lack of plans for maintenance and maintenance/cleaning of the production building. The routine calibration was found to be insufficient in another case, and records of calibration work carried out were even missing completely.
The qualification of production equipment can be found on the list of shortcomings as well. In one case, for example, the missing accuracy check of a tablet test station (hardness, weight) depending on the different possible speed settings as part of the PQ was criticized. Also, the ejection of tablets in relation to the tablet press' different velocities was insufficiently considered in the PQ. In two warning letters issued to companies in China and Taiwan, the qualification of the production equipment was found to be completely absent.
In most cases, though, the warning letters are the response to an insufficiently comprehensive catalogue of measures following the findings in previous inspections. For example, in a case the required calibrations were found to be missing. But the company's reply lacked information regarding the evaluation of the batches on the market that had been manufactured with non-calibrated equipment. In another case - affected was the maintenance and cleaning of a filling line - the evaluation was supposed to be extended to other products which had been manufactured with the faulted system. It is also expected that the newly created maintenance and cleaning plans plus a statement relative to their effectiveness is submitted as well. Somewhat abstruse is the case of another company which had already been noted with regard to the missing or deficient maintenance and cleaning of their facilities in 2001, 2003 and in 2011. In a new FDA inspection in 2012 the appropriate SOPs were still found in draft status.