7 Methods For Airborne Microbial Sampling For Aseptic Manufacturing Environments
Aseptic manufacturing is a series of aseptic processes performed in a sterile environment. An aseptic environment is maintained through specialized equipment that prevents microbial material from technicians, raw materials, or machinery from contaminating medical devices or products.
The terms aseptic and sterile are not synonymous. While both sterile and aseptic products will prevent microbial contamination following use, the processes by which microbial contamination is prevented are different. The term sterile means a complete absence of viable microorganisms or microbes that have the potential to reproduce. Thus, sterile products are often chemically or heat sterilized after being placed in their final packaging. This heat or chemical sterilization process kills any viable microorganisms inside the products (obtained during manufacturing and packaging). The chemical or heat sterilization process after final product packaging is known as terminal sterilization.
On the other hand, an aseptic process is one that prevents contamination by the exclusion of microorganisms. Thus, aseptic healthcare products are made and packaged in a controlled environment designed to prevent microbial contamination of the product. Though the definitions for aseptic and sterile are not the same, sterile is used interchangeably with aseptic. Indeed, many products labeled as sterile are manufactured by aseptic processing rather than terminal sterilization.
What are examples of medical products manufactured in aseptic environments?
- Pharmaceutical sterile products
- Bulk sterile drug substances
- Sterile intermediates
- Excipients
- Medical devices
- Biologics
What is airborne microbial sampling, and why is it important for the environmental monitoring of aseptic manufacturing processes?
It is vital to ensure that aseptic environments maintain an exceptionally low level of microbial contamination. As a result, the air in aseptic environments is regularly sampled for any viable microbes. There are no USP standard methods for air sampling, and air sampling literature indicates that air-sampling methods are highly variable. Thus, when deciding which air sampling methodology to use, do not assume that similar air sample volumes taken by different methods will produce similar rates of microbial recovery. The top seven methods for sampling airborne microbial contaminants are described in detail below.
#1: Slit-to-Agar (STA) Air Sampler
An attached vacuum powers STA samplers. The air intake is obtained through a slit. Underneath the slit, a slowly revolving Petri dish captures any contaminants on a nutrient agar surface. Airborne Viable organisms will grow on the agar plates. Any captured organisms are later characterized and assessed for the volume and type of microorganisms present. On average, slit-to-agar devices have an 80-liters/minute sampling capacity.
#2: Sieve Impactor
Sieve impactors are a popular option for air sampling. Impactors house a container with a nutrient agar Petri dish. The cover of the container housing the petri dish is perforated with openings through which air flows. These perforations provide the “sieve” through which airborne microorganisms are captured. A vacuum pump draws a specific volume of air through the sieve cover. Airborne viable microorganisms are captured by the agar and grow. Some samplers feature nested sieves that contain perforations of decreasing size. Nested sieves sort viable microorganisms by particle size.
#3: Centrifugal Sampler
Centrifugal samplers are one of the most common sampling methods. Centrifugal samplers have a propeller or turbine that gathers a specific air volume into the unit and propels the air to impact a tangentially placed nutrient agar strip. The nutrient agar strip collects any viable microorganisms and is supported by a flexible plastic base.
#4: Sterilizable Microbiological Atrium
The sterilizable microbiological atrium is similar to the single sieve impactor. The cover of the atrium contains uniform holes of 0.25 inches in size. The bottom of the unit contains a Petri dish with nutrient agar. A vacuum pump controls the movement of air through the unit. Atrium systems offer multiple-unit control centers and remote sampling probes.
#5: Surface Air System Sampler
The entry point of the surface air system has an agar plate. Behind the agar plate, a motorized turbine pulls air through the unit’s perforated cover, over the agar contact plate, and out the back of the motor. Any viable microorganisms are captured on the agar plate. On average, surface air sampling devices have a little over 80-liters/minute sampling capacity.
#6: Gelatin Filter Sampler
The gelatin filter sampler has a vacuum pump with an extension hose that ends in a filter holder. The filter consists of gelatin fibers that retain airborne microorganisms. To assay viable microorganisms, the filter is aseptically removed and dissolved in a diluent. The resulting solution is then plated on an agar medium and assessed.
#7: Settling Plates
Settling plates are the most inexpensive way to assess airborne microbes. Settling plates work best for determining environments over prolonged exposure times (4- to 5-hour periods). Settling plates are handy when assessing areas where sampling vacuums are intrusive or hazardous to the aseptic operation. However, settling plates are limited in the volume of air being tested. When the microbial level in the air is expected to contain low contamination levels, at least one cubic meter of air should be tested to maximize sensitivity. With settling plates, exposure to one cubic meter of air cannot be guaranteed, and exposure is based on time instead of a calculated airflow volume.
Summary
Overall, airborne sampling is an important method for environmental monitoring for aseptic manufacturing. Airborne sampling evaluates whether a manufacturing environment is suitable for preventing microbial contamination of medical products during aseptic manufacturing and packaging. Impaction and centrifugal samplers are the most popular forms of airborne sampling. Settling plates are the least expensive sampling method. Air-sampling methods are highly variable. Thus, when deciding which air sampling methodology to use, do not assume that similar air sample volumes taken by different methods will produce similar rates of microbial recovery. If outsourcing environmental monitoring, make sure you choose a contract testing organization that can support you with appropriate environmental monitoring for the aseptic manufacture of your medical device or product.
References
United States Pharmacopeial Convention. <1116> Microbiological Control & Monitoring of Aseptic Processing Environments. Rockville, MD, USA. 2021. (USPC <1116>).
