Due to deficiencies in the design of the filling system as well as the testing for particulate matter, the FDA has issued a warning letter to an Italian manufacturer of sterile products in Rome. The FDA inspection already took place in December of 2016. Because of the non-satisfactory reply in regards to the inspection findings by the manufacturer, the FDA issued the warning letter in July 2017.
The FDA inspectors noticed that smoke studies in the filling area showed turbulent airflow. These flow visualisations are usually performed and recorded during the qualification of the system. In areas where open products are handled or vial caps are not yet crimped, unidirectional airflow is needed in order to protect the product. The smoke study performed a year later also showed turbulent areas in different parts of the filling line. What's more is that - due to a suboptimal system design - the operators have to lean over the open product when they feed the line with sterile closure components. Countless manual manipulations in the production stood out during the inspection, as well, and were noted down by the FDA inspector. The FDA now expects the manufacturer to identify all possible contamination risks in his aseptic production, including analyses of the facility layout, personnel and material flow, air systems and ergonomics of the equipment. On this basis, the manufacturer is to draw up a risk analysis which evaluates the risk of a microbial contamination. Furthermore, he is to describe the measures to be taken in order to reduce those risks.
Another major deficiency is that there's no testing of the product for particulate matter before release. The manufacturer's declaration of intent to introduce this wasn't satisfactory for the FDA. The FDA also demanded a revised product specification as well as written instructions regarding the in-process inspection for visible particles.
Another deficiency was found in sterility testing. Due to the current handling of the samples, there is a danger of microorganisms being inactivated before they can be found during the testing.
More details can be found in the FDA's Warning Letter to Tubilux Pharma.