ENVIRONMENTAL MONITORING
Cleanrooms and controlled environments are utilized in order to control the levels of non-viable and viable particulates that medical devices and pharmaceutical products are exposed to during the manufacturing process. The objective of an environmental monitoring program is to estimate the microbial and particulate content of room air and surfaces. An effective environmental monitoring program can alert you when conditions contributing to excessive microbial levels arise due to ineffective cleaning, sanitation or other personnel/equipment issues. MicroMed can provide you with the appropriate level of service that you need to ensure your manufacturing environment complies with FDA, USP and ISO requirements.
Modifications to Cleanrooms/Controlled Environments should be evaluated to ensure the existing validation is still applicable. Addition of major components, expansion of the room and addition of more personnel and operations in the room can all affect the performance of the room. At the very least Alert and Action levels should be re-evaluated to ensure realistic cleanliness standards are kept within the room and sterilization validations do not become compromised.
MicroMed can also characterize and identify your bacterial or fungal contaminants associated with on-site Environmental Monitoring should a contamination occur.
MicroMed recommends following the EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use for Environmental Monitoring.
Grade A: The local zone for high risk operations, e.g. filling zone, stopper bowls, open ampoules and vials, making aseptic connections. Normally such conditions are provided by a laminar flow work station. Laminar air flow systems should provide a homogeneous air speed in the range of 0.36 – 0.54 m/s (guidance value) at the working position in open clean room applications. The maintenance of laminarity should be demonstrated and validated. A uni-directional air flow and lower velocities may be used in closed isolators and glove boxes.
Grade B: For aseptic preparation and filling, this is the background environment for the grade A zone.
Grade C and D: Clean areas for carrying out less critical stages in the manufacture of sterile products.
Clean Room and Clean Air Device Classification
4. Clean rooms and clean air devices should be classified in accordance with EN ISO 14644-1. Classification should be clearly differentiated from operational process environmental monitoring. The maximum permitted airborne particle concentration for each grade is given in the following table.
| Maximum permitted number of particles per m3 equal to or greater than the tabulated size. |
| |
At Rest |
In Operation |
| Grade |
0.5 µm |
0.5 µm |
0.5 µm |
0.5 µm |
| A |
3,520 |
20 |
3,520 |
20 |
| B |
3,520 |
29 |
3,520 |
29 |
| C |
352,000 |
2,900 |
352,000 |
2,900 |
| D |
3,520,000 |
29,000 |
Not defined |
Not defined |
| Grade |
Examples of operations for terminally sterilized products. |
| A |
Filling of products, when usually at risk. |
| C |
Preparation of solutions, when usually at risk. Filling of products. |
| D |
Preparation of solutions and components for subsequent filling. |
| Grade |
Examples of operations for aseptic preparations. |
| A |
Aseptic preparation and filling. |
| C |
Preparation of solutions to be filtered. |
| D |
Handling of components after washing. |
| Recommended limits for microbial contamination (a) |
| Grade |
Air sample cfu/ m3 |
Settle plates (diameter 90mm) cfu/4hours (b) |
Contact plates (diameter 55mm) cfu/plate |
Glove print 5 fingers cfu/glove |
| A |
<1 |
<1 |
<1 |
<1 |
| B |
10 |
5 |
5 |
5 |
| C |
100 |
50 |
25 |
- |
| D |
200 |
100 |
50 |
- |
(a) These are average values.
(b) Individual settle plates may be exposed for less than 4 hours.
DIY - ENVIRONMENTAL MONITORING KITS
We will help you develop an Environmental Monitoring plan for your cleanroom or controlled environment room based on your room classification and send you a kit to collect your microbial samples. The objective of an environmental monitoring program is to estimate the microbial and particulate content of room air and surfaces. An effective environmental monitoring program can alert you when conditions contributing to excessive microbial levels arise due to ineffective cleaning, sanitation or other personnel/equipment issues. After collection you can mail the media plates back to MicroMed Labs for incubation and enumeration. Once finished we will send you a report with analysis of the samples. MicroMed can provide you with the appropriate level of service that you need to ensure your manufacturing environment complies with FDA, USP and ISO requirements.
MicroMed can also characterize and identify your bacterial or fungal contaminants associated with your Environmental Monitoring should a contamination occur.
PREVENTATIVE MAINTENANCE
Regular and proper HVAC preventive maintenance on clean rooms is absolutely critical. Since all clean rooms run 24 hours a day/ 7 days a week, typical maintenance tasks can be separated into two parts: filter maintenance and equipment maintenance.
Filter maintenance is a key part of clean room support and critical to keep the room within specification. The 24/7 operation of the room puts continuous flow through the filters, causing them to foul faster than equipment that runs on a time schedule. All clean rooms use HEPA filters for the final cleaning of the conditioned air into the space. These are usually preceded by high-density (magnehelic metered) bag (or box) filters, which are then preceded by pre-filters. Because HEPA filters are expensive and time consuming to replace, it's imperative to be diligent in the maintenance of the bag (or box) filters that protect them. Since the bag (or box) filters are somewhat expensive as well, it's also important to frequently replace the pre-filters that protect the bag (or box) filters.
A typical minimum filter replacement schedule for a clean room could be the following:
- Pre-filters - Six times per year
- Bag filters - One time per year
- HEPA filters - Once every three years.
This schedule may need to be adjusted for any particular clean room, as a result of the percentage of outside air that's introduced into the system, as well as the geographic or physical location of the building. Monitoring how dirty the pre-filters are during service, and the changes in magnehelic readings on the bag (or box) filter housings, will ultimately determine the actual frequency of the filter changes.
MicroMed can work closely with the occupants of the clean room, as well as the facilities personnel, this will help you discover the needed frequency of your equipment maintenance.
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