The Critical Role of Continuous Monitoring in Sterile Pharmaceutical Production
In sterile pharmaceutical production, maintaining cleanroom quality is paramount and requires continuous monitoring. Alongside particle measurement, viable monitoring is a key priority. New, automated systems are helping to minimize the risk of contamination while simultaneously increasing productivity – as demonstrated in a retrofit project involving Syntegon and an international Contract Development and Manufacturing Organization (CDMO).
Robust Sterile Processes and Cleanroom Standards
Robust sterile processes are essential to maintaining the quality of parenteral pharmaceuticals. A key factor influencing these processes is the condition of the production environment. Any step involving the aseptic processing of sterile products, ingredients, containers, carriers, or components must take place in a cleanroom environment, as defined in detail by relevant ISO standards and regulations such as EU GMP Annex 1 or FDA GMP Guidance. These standards specify criteria for particle concentration and size to achieve a certain cleanroom class.
Particle Measurement and Viable Monitoring: Two Pillars of Cleanroom Control
Stable quality in the production environment requires controlled temperature and humidity, continuous air exchange, a defined air flow, and regulated positive pressure relative to the environment of lower cleanroom classes. However, even when all these requirements are met, continuous monitoring remains essential to detect deviations at an early stage and ensure consistent cleanroom quality. Particle measurements can be carried out using physical measurement technology, which reliably indicates the size and number of particles per volume element and can warn when defined limit values are exceeded or even shut down production.
Monitoring for microorganisms presents a more complex challenge: individual microorganisms are too small to be detected in real time using microscopic methods or to be reliably distinguished from non-viable particles. However, microbial colonies can be counted and identified when grown on a suitable culture medium. The microbial count can be determined using both active and passive methods.
In active sampling, a defined volume of cleanroom air is continuously or intermittently drawn through a culture medium. In passive sampling, culture media are exposed to the cleanroom environment at critical points in the production process. The sedimentation rate of viable microorganisms per unit of time is then measured using culture medium plates.
Addressing the Challenges of Settle Plates
The placement of culture medium plates required for passive viable monitoring – commonly referred to as settle plates in the pharmaceutical industry – presents several challenges. These plates should be positioned close to critical process steps, such as filling, without obstructing filling equipment or workflow.
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