Continuous Microbiological Environmental Monitoring for Process Understanding and Reduced Interventions in Aseptic Manufacturing

Application of Biofluorescent Particle Counters for Real-Time Bioburden Control in Aseptic Cleanroom Manufacturing

“…One of these substances is 2-propanol, which is widely used in aseptic manufacturing for disinfection purposes. The effect of a false MCP detection by the use of 2-propanol has been observed in previous studies [19,23].…”

“…Other than classic laser particle counters, which detect and classify particles by scattered light analysis, a BFPC also measures the wavelength of the scattered light. Substances found in all microorganisms (bacteria and fungi) are dipicolinic acid, nicotinamid adenine dinucteotide (NADH), and riboflavin [19][20][21]. They create a fluorescent signal that can be detected by the device.…”

“…A direct comparison of BFPC-measured values with CFUs counted on agar plates or strips is hardly possible, as described by several scientists [19,[24][25][26]. The reason for this is the dependency on possible growth on agar plates with CFU methods.…”

“…Though the specific species of microbes is not known at this point, this is still valuable not only during pharmaceutical operations, but also for an evaluation of the operational readiness of a cleanroom in preparation for commissioning and qualification [25]. It would minimize the time required for finding bioburden leaks in the cleanroom installation [2,19,27]. A detriment is that industry-wide recommended action limits for MCPs measured by BFPC systems are not available yet [22].…”

A Discussion on Bio-Fluorescent Particle Counters: Summary of the Process and Environmental Monitoring Methods Working Group Meeting with the FDA Emerging Technology Team

“…BFPC systems for air and water have been used successfully in non-good manufacturing practice (non-GMP) monitoring applications by a number of pharmaceutical companies. Some of these applications or use cases have recently been presented in journal articles and webinars (3)(4)(5)(6)(7)(8)(9)(10)(11). BFPC have not yet been broadly adopted for GMP applications despite the benefits described above.…”