Nonviable particulate and viable microbiological surveillance are used to evaluate the design and control of a cGMP-manufacturing environment. The nonviable particulate monitoring program plays an important role as it is used on a routine basis to verify the maintenance of air classifications.
Microbial Environmental Monitoring
To achieve compliance to regulatory guidance, a microbial monitoring program includes the following components:
- Active air (room or enclosure environment)
- Passive air (settle plates)
- Surfaces (contact plates and swabs)
- Personnel (gloves and garments)
- Compressed gases
- Materials and equipment that could compromise product microbiological quality
- Cleaning and sanitization process understanding
EU GMP 2008 and FDA GMP 2004 describe microbial limits for cleanrooms and are a reference for determining process alert and action limits. Keep in mind no microbial sampling plan can prove the absence of contamination even when nothing viable is recovered. A large proportion of microorganisms are viable but unable to grow on the traditional agar media. Microbial monitoring programs do not guarantee sterility of a given batch by collecting counts under defined specifications. However, they do help demonstrate the manufacturing process is in a continuous state of control.
Devices that Monitor Microbes
For the following active air devices, air is drawn through slits in the sampling head using an internal/external vacuum pump. The microorganisms impact on the agar surface in the same pattern as the sampling head slits.
- Contact/Petri Dish Sieve Impactor: MiniCapt® Mobile Microbial Air Sampler and MiniCapt Remote Microbial Air Sampler. These products have compressed gas applications.
- Sterilizable Atrium Impactor: BioCapt® Stainless Steel Impactor
- Single-Use Sterile Atrium Impactor: BioCapt® Single-Use Impactor
These devices contribute to the overall analysis and control of process microbes.
It should be noted that the microbial monitoring within an EM program does not provide an exact quantity and quality of the microorganisms present in the manufacturing area. Numerous studies have shown that there is a large proportion of microorganisms that are viable but unable to grow on the traditional agar media. Therefore, these microorganisms, known as viable but not culturable (VBNC) are not detected using the traditional methodology.
In addition, traditional methods are unable to sample everywhere and at every time. Instead, this methodology provides observational windows of time. Consequently, the microbial monitoring program is not a way to guarantee the sterility of a given batch by collecting counts under defined specifications, but rather it contributes to demonstrating the manufacturing process is in a continuous state of control.
Download the application note for an in-depth analysis of microbiological control in cleanrooms, including recommendations and discussions on current regulatory practice.