Contamination Control Strategy (CCS) Questions

Answer: Both, for different reasons. Remember that FMEA is a quantitative tool that weighs severity, occurrence and detectability. We need historical data to trend or estimate the likelihood of an event to understand the occurrence portion. Severity and detectability are defined by the consequences and alerts of failures, and requires additional interpretation from an experienced subject matter expert (SME) focused on science-based expectations.

Answer: In my experience, yes. Most vibratory bowls are for feeding, sorting and orientation, so the introduction of a contaminant at this stage is relatively low, especially for an aseptic filling machine. However, it’s still necessary to capture particulate data. We can address the generated particles by revalidating for the appropriate alert and alarm limits of the particle counter in this particular area.

Answer: Vial sealing and capping take place in a Grade A classified area, and the best location for a non-viable counter is where the highest risk of contamination has been determined through a quality risk assessment (QRA). In this assessment, we need to consider the sterile surfaces, sterile equipment, personnel, and product when identifying the risk. If the capping area is inside an isolator or a part of the filling line, this area is classified as Grade A. If the crimping machine is in Grade C with unidirection airflow, this is a Grade A Supply area. According to Annex 1, Grade A air supply is air that’s passed through a filter that capable of producing Grade A non-viable quality air. However, there’s no requirement to perform continuous nonviable monitoring or meet Grade A viable monitoring limits, and the area itself is not classified. The area is used explicitly to protect fully stoppered vials where the cap has not been crimped and the equipment and engineering systems directly impact product quality.

In sum, the QRA should assess the correct position of the particle counter according to the process and design of the area.

Answer: The L-R method could be very useful, but it only allows you to see the sampling point trend. For the new filling line, the fluid dynamical studies help to see all possible impacts for contamination. These impacts are not direct, but carried by the turbulence generated above all inside the insulators.

Answer: For sterile API and finished product, it is necessary to evaluate the presence of endotoxins with the LAL test. The appropriate suit must be defined based on the production process and the operators’ comfort. It must be certified by the manufacturer with low particle release and must be sterile. From a microbiological point of view, each operator must be qualified for the dressing procedure by defining critical sampling points.