The Challenges With Real-Time Viable Particle Counters

Rapid Microbiological Methods (RMM) instruments significantly reduce the time to obtain microbial results from a collected sample. Several manufacturers have recently introduced real-time viable particle detectors which use optical techniques to determine particle viability on a particle-by-particle basis. With this new family of RMM insturments there are significan benefits but also some new challenges associated with evaluating, testing and vailidating.

Real-time viable particle detectors have several key operating parameters, which should be considered and addressed when evaluating and validating real-time viable particle detectors.

• Sample Flow Rate - amount of air that the instrument analyzes
• Aerosol Efficiency - the ratio of the number of particles present in the manufacturing environment
• Sensitivity - the ability to measure low number of viable particle counts
• False Positive Rate - occur due to the non-specific nature of the LIF technique

Evaluation

Current RMM guidance does not appropriately address the critical performance parameters of real-time viable particle detectors. As mentioned previously, current guidance focuses on comparing new laboratory based methods to the compendial culture based method. This guidance addresses the majority of post sample collection laboratory based RMM instruments. Evaluation of real-time viable particle detectors must include the following critical factors:

• How the aerosol is introduced during routine operation as well as laboratory based evaluation
• The aerosol efficiency of the real-time viable particle detector
• The aerosol efficiency of the active sampler used to obtain the comparison sample
• The detection efficiency of the real-time viable particle detector
• The false positive rate of the real-time viable particle detector

The challenges associated with evaluating this new family of RMM instrumentation are directly related to the benefit they offer to the manufacturing process: the ability to measure for the presence of viable organisms on a real-time basis. The FDA aseptic processing guidelines states: “Manufacturers should be aware of a device’s air monitoring capabilities, and the air sampler should be evaluated for its suitability for use in an aseptic environment based on collection efficiency, clean ability, ability to be sterilized, and disruption of unidirectional airflow” (Guidance for Industry Sterile Drug Products Produced by Aseptic Processing-Current Good Manufacturing Practice FDA 2004). Similar awareness and understanding needs to be developed for real-time viable particle detectors.