Environmental Monitoring Equipment in Sterile Bio-Pharmaceutical Manufacturing Facilities
According to 21 CFR 211.42, cGMP for Finished Pharmaceuticals-Design and Construction Features, “a system for monitoring environmental conditions” must be established in a drug manufacturing facility. Environmental conditions inside the facilities must be monitored at a validated pre determined frequency and document the results. Quality Control units of pharmaceutical manufacturers are usually responsible for performing environmental monitoring (EM). QC associates use various equipment to collect environmental monitoring samples.
Viable surface, viable air, and non-viable particulate air samples are required to be sampled in sterile drug manufacturing facilities by ISO 14644 and USP Chapter 1116. Viable surface samples are collected using Replicate Organism Detection and Counting (RODAC) plates. These RODAC plates are circular in shape and have agar covered by a lid. QC associate would open the lid and touch the agar on desired surfaces. RODACs filled with two types of agar are usually used for EM. Trypticase Soy Agar (TSA) is used to detect bacteria and Saboroaud Dextrose Agar (SAB) is used to detect mold and yeast. TSA RODACs are more frequently used in EM while SAB RODACs are only used less frequently (mostly used in critical filling areas in conjunction with TSA RODACs). Per USP, TSA plates are usually incubated three to five days and SAB plates usually incubated for 7 to 10 days. If additional incubation periods are required, possibly due to weekend and/or holiday coverage, incubation periods longer than above can be validated via test method validation.
Slit to Agar (STA) machines are used for viable air sampling. STA machines use a large 150mm TSA plate for collecting viable microorganisms in the room air. They have a vacuum pump, a plastic dome cover, and a small slit in the dome cover. When the machine is in use, the vacuum pump sucks in the room air through the slit and microorganisms, if they are present in the air, are deposited onto the large TSA plate. The plate is incubated for 3 to 5 days and result is read. Viable air samples are run usually for 50 minutes per sample. That means that TSA plate has 50 minutes of sampling and 10 minutes of control. In other words, 5/6 of the TSA plate would be exposed to room air and the remaining 1/6 of the plate would serve as control.
Viable monitoring using STA samples are usually used in non-critical rooms where only one sample plate is required. But in critical areas, such as compounding and filling rooms, continuous viable monitoring is required while critical manufacturing activities are being performed. For continuous viable air monitoring in critical areas, Sterilizable Microbial Atrium (SMA) systems are used. SMA have a vacuum pump, 100mm TSA plates, and the plates usually have 32mL of TSA. According to USP, sampling time for a 32 mL TSA is three hours.
Met One laser particle counters are used in sampling non-viable particles in the manufacturing rooms’ air. MetOnes also have vacuum pump which suck in air through a laser counter which counts for small particles 0.5 micrometer and 5.0 micrometer in size. In noon critical areas, only 10 minutes of MetOne samples are required but in critical areas, continuous monitoring is required. MetOnes can be programmed to collect non viable air samples continuously.
On my next blog, I will talk about determining alert and action levels of manufacturing rooms.
Sources
21 CFR 211.42, “Design and construction features”.
