Air velocity measurement
As part of risk assessment this evaluation should also consider the selection of locations for the critical control points for monitoring air velocity as well as viable and non-viable particles.
1. Problem Statement-
Where should airflow velocity measurements be taken with respect to a filling line or other aseptic processing areas?
Recommendation
Airflow velocity measurements should be taken at locations where meaningful and reproducible results can be obtained. This is typically at a distance of 6 inches from the filter face.
Rationale for Recommendation
The primary reason for airflow velocity measurements in unidirectional airflow areas (e.g., areas where product, product contact packaging components, and product contact surfaces are exposed) is to assure there is adequate airflow to protect the materials from external airborne contamination.
Accurate measurements can be taken and changes over time detected when airflow velocities are evaluated six inches from the filter face.
This data should be supplemented with smoke study (airflow pattern study) data to provide evidence of adequate protection of the aseptic process.
The optimal airflow velocity depends on the design of the filling line, room design and air handling system. This can be determined from airflow velocity and airflow pattern studies. Once determined, it is important to ensure the velocity stays within the specified parameters. Routine air velocity measurements should be taken at the same locations determined during the initial airflow studies to ensure consistency.
2. Problem Statement-
Is an airflow velocity of 90 ft./min. (0.457 m/s) +/- 20% a requirement when measured within 6” of the filter face?
Recommendation
Airflow velocity should be sufficient to protect exposed product, product contact packaging components, and product contact surfaces from potential environmental contamination especially at working positions / heights. Any airflow velocity demonstrated and specified to accomplish this is acceptable.
Rationale for Recommendation
Optimum airflow velocity is highly dependent on the configuration of the HVAC system and the production facilities, including filling and packaging lines. Velocity should be optimized at a value that results in airflow patterns that protect exposed product, product contact packaging components, and product contact surfaces from airborne contamination especially at working positions / heights. Once established, ongoing velocity measurements should be constant, within defined limits.
3. Problem Statement-
When do velocity measurements have to be taken?
Recommendation
Airflow velocity measurements should be taken during operational and performance qualification studies. Frequency of routine monitoring should be at least annually. HEPA filters in critical areas should be tested semi-annually. More frequent measurements may be appropriate if other measures of clean room quality indicate a significant deviation. Airflow pattern studies should be repeated when any changes are made that might have an impact on the velocity measurements outside validated acceptance criteria (i.e., changes to air handling systems, aseptic processing equipment, HEPA filters). Evaluation of such impact should be made following applicable change management procedures. Airflow measurements can be area or line-specific.
Rationale for Recommendation
Airflow velocity is measured to ensure adequate airflow to protect exposed product, product contact packaging components, and product contact surfaces. It is also measured to ensure there have been no significant changes to the HVAC system. Airflow criteria are established during qualification studies.
4. Problem Statement-
Must a differential pressure of 0.05" WG (0.012 kPa) water be maintained between zones of different air cleanliness classification?
Recommendation
Typically, pressure differentials between 0.03" and 0.05" WG (7 and 12 Pa) water are effective. Other pressure differentials may be used if data are available to support the chosen value. The primary objective is to maintain positive pressure between zones of different air cleanliness classification. Transitory variations are acceptable as doors are opened and closed as long as the proper airflow direction is maintained.
Rationale for Recommendation
Differential pressures are necessary to control the airflow between adjacent, connected areas of different air cleanliness classification. Room air pressures also influence the number of air changes and supply velocities. Data (e.g., airflow pattern studies, physical measurements) should be available to support the adequacy of the chosen pressure differentials.
5. Problem Statement-
What is the frequency with which HEPA filters should be tested?
Recommendation
HEPA filters should be tested for leaks and pressure drop at least annually unless there is information to support the need for a different frequency. HEPA filters in Grade A environments should be tested semi-annually.
Rationale for Recommendation
It is established industry practice to test HEPA filters at least annually. This practice is based on extensive experience with the use of HEPA filters in the field.
6. Problem Statement-
Can HEPA filters be patched? If so, what is the maximum allowable patch size?
Recommendation
Yes, HEPA filters can be patched with RTV silicone or other suitable material as long as filter integrity is restored and the airflow volume and velocity through the filter is not significantly affected (i.e., room pressure differentials, airflow patterns remain as validated).
Repairs to the HEPA filter may be performed providing:
• The size of the repair or repairs does not block or restrict more than 3% of the filters face area (not including the frame), and • The lesser dimension of any repair does not exceed 3.8 cm (1.5 in.), or as otherwise agreed upon by the buyer and the seller.
Rationale for Recommendation
There is significant industrial history to show that HEPA filters so patched do not adversely affect the operation of the facility or equipment in which they are installed.
7. Problem Statement-
What are the recommended alert and action levels for aseptic processing areas?
Recommendation
Each manufacturer should have a formal program which stipulates the environmental monitoring alert and action levels and the methods used to determine them.
Published action levels exist and should be considered as the company designs its EM program. The table provided contains guidelines provided by the agencies stated. These are “starting points” or “targets” in some cases or are required regulations to be met in other cases. Where regulatory guidance is not provided action limits should be based on historical data, as discussed for the establishment of alert levels below.
Alert levels should be based on historical data. For new facilities, production lines, or other aseptic processing areas where historical data are not available, alert levels can be set based on similar aseptic processing areas within the facility or at another facility; or by using environmental data generated during validation studies. In any of these instances, environmental monitoring data from the new area will be generated and should be used to reset the alert levels. Periodically thereafter, data should be reviewed, and if needed, alert levels may be adjusted (e.g., tighter or looser) based on the historical data. Caution should be given when tightening limits to a level that approaches process capability. See PDA Technical Report No. 13 (Revised), “Fundamentals of an Environmental Monitoring Program” Sept/Oct 2001 for several methods of setting alert and action levels using historical data.
Environmental monitoring alert and action levels should be used to monitor and control aseptic processes. They should not be treated as specification (pass/fail) limits. The significance of the environmental monitoring program lies in its ability to identify adverse trends and deviations from the established norm. The absolute value of any particular value is of limited scientific meaning.
Mold does not carry “special” status relative to bacteria. Any significant shifts in type or number require action. The approach to prevention/avoidance of contamination of Grade A environments should focus on eliminating the cause of the contamination (its source) not merely on addressing the symptom.
Rationale for Recommendation
ISO 13048-1 states that, “…Alert and action levels should be derived from and consistent with results obtained during the aseptic process validation. Historical data from routine monitoring may also be appropriate for use in setting alert and action levels.”
The following table is a compilation of some published microbial environmental guidelines. See references for additional information.
a These levels are average values. b Contact plate areas vary from 24-30 cm2
1. Problem Statement-
Where should airflow velocity measurements be taken with respect to a filling line or other aseptic processing areas?
Recommendation
Airflow velocity measurements should be taken at locations where meaningful and reproducible results can be obtained. This is typically at a distance of 6 inches from the filter face.
Rationale for Recommendation
The primary reason for airflow velocity measurements in unidirectional airflow areas (e.g., areas where product, product contact packaging components, and product contact surfaces are exposed) is to assure there is adequate airflow to protect the materials from external airborne contamination.
Accurate measurements can be taken and changes over time detected when airflow velocities are evaluated six inches from the filter face.
This data should be supplemented with smoke study (airflow pattern study) data to provide evidence of adequate protection of the aseptic process.
The optimal airflow velocity depends on the design of the filling line, room design and air handling system. This can be determined from airflow velocity and airflow pattern studies. Once determined, it is important to ensure the velocity stays within the specified parameters. Routine air velocity measurements should be taken at the same locations determined during the initial airflow studies to ensure consistency.
2. Problem Statement-
Is an airflow velocity of 90 ft./min. (0.457 m/s) +/- 20% a requirement when measured within 6” of the filter face?
Recommendation
Airflow velocity should be sufficient to protect exposed product, product contact packaging components, and product contact surfaces from potential environmental contamination especially at working positions / heights. Any airflow velocity demonstrated and specified to accomplish this is acceptable.
Rationale for Recommendation
Optimum airflow velocity is highly dependent on the configuration of the HVAC system and the production facilities, including filling and packaging lines. Velocity should be optimized at a value that results in airflow patterns that protect exposed product, product contact packaging components, and product contact surfaces from airborne contamination especially at working positions / heights. Once established, ongoing velocity measurements should be constant, within defined limits.
3. Problem Statement-
When do velocity measurements have to be taken?
Recommendation
Airflow velocity measurements should be taken during operational and performance qualification studies. Frequency of routine monitoring should be at least annually. HEPA filters in critical areas should be tested semi-annually. More frequent measurements may be appropriate if other measures of clean room quality indicate a significant deviation. Airflow pattern studies should be repeated when any changes are made that might have an impact on the velocity measurements outside validated acceptance criteria (i.e., changes to air handling systems, aseptic processing equipment, HEPA filters). Evaluation of such impact should be made following applicable change management procedures. Airflow measurements can be area or line-specific.
Rationale for Recommendation
Airflow velocity is measured to ensure adequate airflow to protect exposed product, product contact packaging components, and product contact surfaces. It is also measured to ensure there have been no significant changes to the HVAC system. Airflow criteria are established during qualification studies.
4. Problem Statement-
Must a differential pressure of 0.05" WG (0.012 kPa) water be maintained between zones of different air cleanliness classification?
Recommendation
Typically, pressure differentials between 0.03" and 0.05" WG (7 and 12 Pa) water are effective. Other pressure differentials may be used if data are available to support the chosen value. The primary objective is to maintain positive pressure between zones of different air cleanliness classification. Transitory variations are acceptable as doors are opened and closed as long as the proper airflow direction is maintained.
Rationale for Recommendation
Differential pressures are necessary to control the airflow between adjacent, connected areas of different air cleanliness classification. Room air pressures also influence the number of air changes and supply velocities. Data (e.g., airflow pattern studies, physical measurements) should be available to support the adequacy of the chosen pressure differentials.
5. Problem Statement-
What is the frequency with which HEPA filters should be tested?
Recommendation
HEPA filters should be tested for leaks and pressure drop at least annually unless there is information to support the need for a different frequency. HEPA filters in Grade A environments should be tested semi-annually.
Rationale for Recommendation
It is established industry practice to test HEPA filters at least annually. This practice is based on extensive experience with the use of HEPA filters in the field.
6. Problem Statement-
Can HEPA filters be patched? If so, what is the maximum allowable patch size?
Recommendation
Yes, HEPA filters can be patched with RTV silicone or other suitable material as long as filter integrity is restored and the airflow volume and velocity through the filter is not significantly affected (i.e., room pressure differentials, airflow patterns remain as validated).
Repairs to the HEPA filter may be performed providing:
• The size of the repair or repairs does not block or restrict more than 3% of the filters face area (not including the frame), and • The lesser dimension of any repair does not exceed 3.8 cm (1.5 in.), or as otherwise agreed upon by the buyer and the seller.
Rationale for Recommendation
There is significant industrial history to show that HEPA filters so patched do not adversely affect the operation of the facility or equipment in which they are installed.
7. Problem Statement-
What are the recommended alert and action levels for aseptic processing areas?
Recommendation
Each manufacturer should have a formal program which stipulates the environmental monitoring alert and action levels and the methods used to determine them.
Published action levels exist and should be considered as the company designs its EM program. The table provided contains guidelines provided by the agencies stated. These are “starting points” or “targets” in some cases or are required regulations to be met in other cases. Where regulatory guidance is not provided action limits should be based on historical data, as discussed for the establishment of alert levels below.
Alert levels should be based on historical data. For new facilities, production lines, or other aseptic processing areas where historical data are not available, alert levels can be set based on similar aseptic processing areas within the facility or at another facility; or by using environmental data generated during validation studies. In any of these instances, environmental monitoring data from the new area will be generated and should be used to reset the alert levels. Periodically thereafter, data should be reviewed, and if needed, alert levels may be adjusted (e.g., tighter or looser) based on the historical data. Caution should be given when tightening limits to a level that approaches process capability. See PDA Technical Report No. 13 (Revised), “Fundamentals of an Environmental Monitoring Program” Sept/Oct 2001 for several methods of setting alert and action levels using historical data.
Environmental monitoring alert and action levels should be used to monitor and control aseptic processes. They should not be treated as specification (pass/fail) limits. The significance of the environmental monitoring program lies in its ability to identify adverse trends and deviations from the established norm. The absolute value of any particular value is of limited scientific meaning.
Mold does not carry “special” status relative to bacteria. Any significant shifts in type or number require action. The approach to prevention/avoidance of contamination of Grade A environments should focus on eliminating the cause of the contamination (its source) not merely on addressing the symptom.
Rationale for Recommendation
ISO 13048-1 states that, “…Alert and action levels should be derived from and consistent with results obtained during the aseptic process validation. Historical data from routine monitoring may also be appropriate for use in setting alert and action levels.”
The following table is a compilation of some published microbial environmental guidelines. See references for additional information.
a These levels are average values. b Contact plate areas vary from 24-30 cm2
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