Managing the transition from the new paradigm of in-process control using continuous biofluorescent particle counters from the traditional growth-based air monitoring is a difficult challenge requiring a comprehensive regulatory strategy. This is best approached within confines of the concept of process analytical technology. A five-stage approach to the evaluation, validation, test runs and data analysis, regulatory approval, and implementation is recommended. Critical to the implementation is the application of the safe harbor concept to avoid non-compliance issues.