Transcript
Pharmaceutical Cleanroom HVAC Ventilation Rate Study Authors Thomas R. Spearman Consultant Engineer IPPO Plant Engineering
Donald R Moore Associate Senior Consultant Engineer Engineering Technical Center
Rebecca J Elliott Research Scientist MS&T Statistics
Eli Lilly and Company Lilly Corporate Center Indianapolis, IN 46285
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Abstract The objective of this experiment was to challenge design practices that utilize high ventilation (air change) rates to maintain particulate levels within classified spaces. This experiment was designed to produce sufficient independent data on the correlation of ventilation rate to both particulate control (within classification limits) and recovery time (clean up from “in operation” particulate levels to one or two orders of magnitude cleaner when “at rest”). This study, which was performed in a pilot p ilot facility at Eli Lilly, as part of a pharmaceutical industry wide ‘Green’ Pharma HVAC Team initiative aimed at reducing HVAC energy costs while maintaining GM GMP P compliance within the cleanroom. The team’s plan is to execute similar studies in other pharma cleanrooms to develop guidelines for the industry for more sustainable HVAC systems. The conclusions of this study are: • For this application, the room recovery rate test is a good measure of cleanroom performance. The theoretical equation provided good estimates of the actual performance. However, at an Adjustable Speed Drive (ASD) setting of 15 Hz (seven air changes per hour), the theoretical equation provided poor estimates of the actual performance. • A more consistent method of generating particles is needed for future testing. The generation rate needs to be independently determined or measured instead of using the equation based on supply air volume used in this report.
Page 2 of 55
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Abstract The objective of this experiment was to challenge design practices that utilize high ventilation (air change) rates to maintain particulate levels within classified spaces. This experiment was designed to produce sufficient independent data on the correlation of ventilation rate to both particulate control (within classification limits) and recovery time (clean up from “in operation” particulate levels to one or two orders of magnitude cleaner when “at rest”). This study, which was performed in a pilot p ilot facility at Eli Lilly, as part of a pharmaceutical industry wide ‘Green’ Pharma HVAC Team initiative aimed at reducing HVAC energy costs while maintaining GM GMP P compliance within the cleanroom. The team’s plan is to execute similar studies in other pharma cleanrooms to develop guidelines for the industry for more sustainable HVAC systems. The conclusions of this study are: • For this application, the room recovery rate test is a good measure of cleanroom performance. The theoretical equation provided good estimates of the actual performance. However, at an Adjustable Speed Drive (ASD) setting of 15 Hz (seven air changes per hour), the theoretical equation provided poor estimates of the actual performance. • A more consistent method of generating particles is needed for future testing. The generation rate needs to be independently determined or measured instead of using the equation based on supply air volume used in this report.
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Purpose The objective of this experiment was to challenge design practices that utilize high ventilation (air change) rates to maintain particulate levels within classified spaces. This experiment was designed to produce sufficient independent data on the correlation of ventilation rate to both particulate control (within classification limits) and recovery (clean up from “in operation” particulate levels to one or two orders of magnitude cleaner when “at rest”) time. The intent is to provide robust data for review by regulators and industry, thus encouraging investigation at a company level helping drive the industry to a science based assessment of the actual air change requirements, being more energy efficient and thus reducing operating costs (energy, filters, maintenance) in the process.
Tests Executed This testing measured the room particulate concentrations with an aerosol (particle) challenge at varying ventilation rates. It also measured the recovery recovery time after the aerosol challenge was stopped. The testing was performed with the room equipment not operating, so that this was a test of the the HVAC system only. The testing was conducted per the pre-approved protocol. Testing was performed in the Cartridge Prep room at an Eli Lilly Pilot Plant, located from 22-Mar-2010 to 25-Mar-2010. Test equipment calibration and HEPA filter integrity tests were verified to be current. The HVAC system smoke detectors were disabled. The ventilation rate was varied using a remote keypad that changed the adjustable speed drive (ASD) setpoint on air handling unit (AHU) 5. For each ASD setting, the volumetric airflow rates for the room terminal HEPA filters and return grilles were measured and recorded. The room dimensions were measured measured and recorded. This information was used to calculate the room volume. The room volume includes includes the volume occupied by equipment. In other words, the equipment volume was not deducted from the room volume.
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
For each ASD setting, the following data was collected. • Room differential pressure relative to the adjacent mechanica l room (room 16A) • Terminal HEPA volumetric airflow rate in cubic feet per minute (cfm) • Return air volumetric airflow rate in cubic feet per minute (cfm) • Particle counts for 0.5 micron particles and larger and 5 micron particles and larger were recorded in one minute intervals. This data was collected in two separate locations. Dilutors with a 10:1 ratio were used on the particle particle counters to allow for higher particle counts. The room layout with the equipment, motor control center (MCC), low level (LL) return, terminal HEPA, particle counter, and particle generator outlet (P) locations are shown in Figure 1. The particle counter designations (ID#) are also shown. The adjacent mechanical room was used as the reference for differential pressure measurements.
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study Figure 1: Cartridge Prep Room Layout
LL Return
MCC
HEPA MCC
ID# ID# 1
HEPA
HEPA
PPG
Mech Room
ID# ID# 2
HEPA
HEPA HEPA LL Return
Tunnel
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study An ATI model TDA-6C aerosol generator was used as the particle generator. A hose was attached to the generator outlet. A partially opened diaphragm valve was placed on the end of the hose to reduce the particle generation rate. The valve position was determined and set during preliminary testing and was not readjusted during subsequent testing. The valve outlet was elevated approximately four feet above the floor. The Laskin nozzle pressure was set at 3 psig. The generator was started and stopped remotely, outside of the test room. Thirteen test runs were conducted. Run 13 was conducted as a replacement for Run 11 because the particle counter ran out of paper during Run 11. Table A lists the run number, adjustable speed drive (ASD) setting, and test da te.
Table A: Run ASD Settings and Test Dates Run # ASD setting Preliminary Various 1 60 2 15 3 45 4 30 5 15 6 30 7 60 8 45 9 45 10 60 11 30 12 15 13 30
Test Date 22-Mar-2010 23-Mar-2010 23-Mar-2010 23-Mar-2010 23-Mar-2010 24-Mar-2010 24-Mar-2010 24-Mar-2010 24-Mar-2010 25-Mar-2010 25-Mar-2010 25-Mar-2010 25-Mar-2010 25-Mar-2010
Here are the protocol departures. They do not affect the test results. • Datasheets 3 and 4 were not used to setup the particle counters. The particle counters were setup by the Environmental Monitoring group. • The room does not have a routine cleaning procedure. This was marked as not applicable on Datasheet 5 Step 2. • A partially open diaphragm valve was added to the outlet of the particle generator to reduce the particle generation rate. • The room temperature and humidity were not recorded for runs 1 and 4. The particle counters also recorded the room temperature and humidity. This was marked as not applicable on Datasheet 6 Step 4. • The exact location of the particle counters was not measured and recorded per Datasheet 6 Step 6. The approximate locations are shown on Sketch 2 in the protocol and Figure 1 of this report. • The particle generator operation test duration was c hanged from 30 minutes to 15 minutes after preliminary testing. Page 6 of 55
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
•
The ID#1 particle counter ran out of paper during run 11 at minute 41. Run 13 was conducted as a replacement for Run 11.
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Analysis The testing was divided into three time intervals: minute 1 to minute 10, minute 11 to minute 25, and minute 26 to minute 45. From minute 1 to minute 10, personnel were not present and the particle generator was not operating. This time period was used to determine At-Rest particle concentrations. From minute 11 to minute 25, the particle generator was in operation. This time period was used to determine average particle concentrations. From minutes 26 to 45, the particle generator was stopped. This time period was used to determine the two log reduction recovery time. The two log reduction recovery time is the time to achieve a 100 to1 reduction in 0.5 micron particle concentration. For each ASD setting, the following data was determined or calculated. • Maximum 0.5 micron particle concentration • Average 0.5 micron particle concentration • At rest 0.5 micron particle concentration • Supply air volumetric flow rate • Maximum particle generation rate • Average particle generation rate • Air change rate in changes per hour • Actual two log reduction recovery time in minutes • Theoretical two log reduction time in minutes • Difference between actual two log reduction recovery time and theoretical in minutes The maximum 0.5 micron particle concentration (Cmax) is the largest 0.5 micron particle concentration at any time during the run (between minutes 1-45). The average 0.5 micron particle concentration (Cavg) is the average of the 0.5 micron particle concentrations for the last five minutes when the particle generator was operating (minutes 21-25). The actual two log reduction recovery time (R act ) was determined by inspecting the particle concentration data in tabular form. When a two log reduction was not achieved in the case of low air change rates, the single log reduction recovery time was determined and multiplied by 2 to calculate the two log reduction recovery time.
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
The maximum particle generation rates (PGR max) are calculated using the following 1 equation .
Where: PGR max = maximum particle generation rate in particles per minute Cmax = maximum particle concentration (minutes 1-45) in particles per cubic foot Q = supply air volumetric flow rate in cubic feet per minute (cfm)
The average particle generation rates (PGR avg) are calculated using the following 1 equation .
Where: PGR avg = average particle generation rate in particles per minute Cavg = average particle concentration (minutes 21-25) in particles per cubic feet 3 (ft ) Q = supply air volumetric flow rate in cubic feet per minute 1
The air change rates (N) are calculated using the following equation .
60
Where: N = air change rate in changes per hour Q = supply air volumetric flow rate in cubic feet per minute V = room volume in cubic feet
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
The theoretical two log reduction recovery times (R th ) are calculated using the following 2 equation .
⎛ 1 ⎞ − 60 × ln⎜ ⎟ 100 ⎠ ⎝ Rth = N
Where: R th = theoretical two log reduction recovery time in minutes N = air change rate in changes per hour
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Results for Individual Tests Table B summarizes the recorded, measured, and calculated values for each run and particle counter location. For the thirteen test runs, Figures 2-14 plot the 0.5 micron particle concentrations, 5 micron particle concentrations for both particle counter locations. The time the particle generator (PG) is turned on and turned off are indicated.
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Table B: Run Data and Calculated Values Run #
ASD
ID#
Cmax
Cavg
Cr
Q
V
PGRmax
PGRavg
N
Ract
Rth
Ract‐Rth difference
ASD setting
max 0.5
in
particle
particle
at rest
volumetric
generation
generation
air change
actual 2 log
2 log
pts 0.5
particles
flow rate in
room
rate in
rate in
rate in
recovery
recovery
time and
per cubic
cubic feet
volume in
particles
particles per
changes
time in
time in
theoretical in
per minute
cubic feet
per minute
minute
per hour
minutes
minutes
minutes
particles per particles per
Hertz
cubic foot
theoretical between actual
supply air average of 5
cubic foot
foot
2 log recovery
1
60
1
40,730
30,748
1
2881
3527
1.17E+08
8.86E+07
49.0
9
5.6
3. 4
1
60
2
51,710
36,478
1
2881
3527
1.49E+08
1.05E+08
49.0
9
5.6
3.4
2
15
1
112,727
97,197
737
420
3527
4.73E+07
4.08E+07
7.1
36
38.7
2
15
2
127,580
85,350
80
420
3527
5.36E+07
3.58E+07
7.1
30
38.7
‐ 2.7 ‐ 8.7
3
45
1
248,450
215,864
1
2032
3527
5.05E+08
4.39E+08
34.6
11
8.0
3.0
3
45
2
152,180
138,062
1
2032
3527
3.09E+08
2.81E+08
34.6
11
8.0
3.0
4
30
1
312,370
257,758
110
1199
3527
3.75E+08
3.09E+08
20.4
14
13.5
0.5
4
30
2
1,206,530
840,695
10
1199
3527
1.45E+09
1.01E+09
20.4
13
13.5
5
15
1
1,387,630
1,329,324
540
405
3527
5.62E+08
5.38E+08
6.9
26
40.1
5
15
2
1,767,430
1,498,644
530
405
3527
7.16E+08
6.07E+08
6.9
26
40.1
6
30
1
620,660
56,886
1
1193
3527
7.40E+08
6.79E+07
20.3
13
13.6
6
30
2
586,970
457,818
1
1193
3527
7.00E+08
5.46E+08
20.3
12
13.6
‐ 0.5 ‐ 14.1 ‐ 14.1 ‐ 0.6 ‐ 1.6
7
60
1
84,590
41,926
1
2733
3527
2.31E+08
1.15E+08
46.5
9
5.9
3.1
7
60
2
112,480
51,040
1
2733
3527
3.07E+08
1.39E+08
46.5
9
5.9
3.1
8
45
1
42,909
11,526
1
1972
3527
8.46E+07
2.27E+07
33.5
11
8.2
2.8
8
45
2
63,970
53,256
1
1972
3527
1.26E+08
1.05E+08
33.5
11
8.2
2.8
9
45
1
574,370
47,610
1
2015
3527
1.16E+09
9.59E+07
34.3
9
8.1
0.9
9
45
2
747,350
355,496
30
2015
3527
1.51E+09
7.16E+08
34.3
9
8.1
0.9
10
60
1
88,960
53,258
1
2805
3527
2.50E+08
1.49E+08
47.7
8
5.8
2.2
10
60
2
104,820
66,492
1
2805
3527
2.94E+08
1.87E+08
47.7
8
5.8
2.2
11
30
1
245,091
39,418
70
1197
3527
2.93E+08
4.72E+07
20.4
18
13.6
4.4
11
30
2
864,130
702,218
60
1197
3527
1.03E+09
8.41E+08
20.4
14
13.6
0.4
12
15
1
332,131
24,404
3,200
442
3527
1.47E+08
1.08E+07
7.5
34
36.7
12
15
2
549,640
476,074
490
442
3527
2.43E+08
2.10E+08
7.5
22
36.7
‐ 2.7 ‐ 14.7
13
30
1
388,657
20,538
140
1217
3527
4.73E+08
2.50E+07
20.7
14
13.3
0.7
13
30
2
746,370
601,772
1
1217
3527
9.08E+08
7.32E+08
20.7
13
13.3
‐ 0.3
Note: Run 11 is excluded from analysis due to the particle counter running out of paper.
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 2: Run 1 Plot
Run 1 60 Hertz 1.00E+05
PG on
PG off
1.00E+04
1.00E+03 ID#1 0.5 micron per ft3 ID#2 0.5 micron per ft3 1.00E+02
ID#1 5.0 micron per ft3 ID#2 5.0 micron per ft3
1.00E+01
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 2: Run 1 Plot
Run 1 60 Hertz 1.00E+05
PG off
PG on
1.00E+04
1.00E+03 ID#1 0.5 micron per ft3 ID#2 0.5 micron per ft3 1.00E+02
ID#1 5.0 micron per ft3 ID#2 5.0 micron per ft3
1.00E+01
1.00E+00 1
3
5
7
9
11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 Minute
Page 13 of 55
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 3: Run 2 Plot
Run 2 15 Hertz 1.00E+06
PG on
PG off
1.00E+05
1.00E+04
1.00E+03
ID#1 0.5 micron per ft3 ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3
1.00E+02
1.00E+01
ID#2 5.0 micron per ft3
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 3: Run 2 Plot
Run 2 15 Hertz 1.00E+06
PG off
PG on
1.00E+05
1.00E+04
ID#1 0.5 micron per ft3
1.00E+03
ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3 1.00E+02
ID#2 5.0 micron per ft3
1.00E+01
1.00E+00 1
3
5
7
9
11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 Minute
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 4: Run 3 Plot
Run 3 45 Hertz 1.00E+06 PG on
PG off
1.00E+05
1.00E+04
1.00E+03
ID#1 0.5 micron per ft3 ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3
1.00E+02
1.00E+01
ID#2 5.0 micron per ft3
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 4: Run 3 Plot
Run 3 45 Hertz 1.00E+06 PG on
PG off
1.00E+05
1.00E+04
ID#1 0.5 micron per ft3
1.00E+03
ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3 1.00E+02
ID#2 5.0 micron per ft3
1.00E+01
1.00E+00 1
3
5
7
9
11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 Minute
Page 15 of 55
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 5: Run 4 Plot
Run 4 30 Hertz 1.00E+07
PG on
PG off
1.00E+06
1.00E+05
1.00E+04 ID#1 0.5 micron per ft3 1.00E+03
ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3
1.00E+02
1.00E+01
ID#2 5.0 micron per ft3
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 5: Run 4 Plot
Run 4 30 Hertz 1.00E+07
PG on
PG off
1.00E+06
1.00E+05
1.00E+04 ID#1 0.5 micron per ft3 ID#2 0.5 micron per ft3
1.00E+03
ID#1 5.0 micron per ft3 ID#2 5.0 micron per ft3
1.00E+02
1.00E+01
1.00E+00 1
3
5
7
9
11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 Minute
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 6: Run 5 Plot
Run 5 15 Hertz 1.00E+07
PG on
PG off
1.00E+06
1.00E+05
1.00E+04 ID#1 0.5 micron per ft3 1.00E+03
ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3
1.00E+02
1.00E+01
ID#2 5.0 micron per ft3
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 6: Run 5 Plot
Run 5 15 Hertz 1.00E+07
PG off
PG on
1.00E+06
1.00E+05
1.00E+04 ID#1 0.5 micron per ft3 ID#2 0.5 micron per ft3
1.00E+03
ID#1 5.0 micron per ft3 ID#2 5.0 micron per ft3
1.00E+02
1.00E+01
1.00E+00 1
3
5
7
9
11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 Minute
Page 17 of 55
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 7: Run 6 Plot
Run 6 30 Hertz 1.00E+06
PG on
PG off
1.00E+05
1.00E+04
1.00E+03
ID#1 0.5 micron per ft3 ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3
1.00E+02
1.00E+01
ID#2 5.0 micron per ft3
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 7: Run 6 Plot
Run 6 30 Hertz 1.00E+06
PG off
PG on
1.00E+05
1.00E+04
ID#1 0.5 micron per ft3
1.00E+03
ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3 1.00E+02
ID#2 5.0 micron per ft3
1.00E+01
1.00E+00 1
3
5
7
9
11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 Minute
Page 18 of 55
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 8: Run 7 Plot
Run 7 60 Hertz 1.00E+06
PG on
PG off
1.00E+05
1.00E+04
1.00E+03
ID#1 0.5 micron per ft3 ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3
1.00E+02
1.00E+01
ID#2 5.0 micron per ft3
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 8: Run 7 Plot
Run 7 60 Hertz 1.00E+06
PG on
PG off
1.00E+05
1.00E+04
ID#1 0.5 micron per ft3
1.00E+03
ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3 1.00E+02
ID#2 5.0 micron per ft3
1.00E+01
1.00E+00 1
3
5
7
9
11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 Minute
Page 19 of 55
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 9: Run 8 Plot
Run 8 45 Hertz 1.00E+05
PG on
PG off
1.00E+04
1.00E+03 ID#1 0.5 micron per ft3 ID#2 0.5 micron per ft3 1.00E+02
ID#1 5.0 micron per ft3 ID#2 5.0 micron per ft3
1.00E+01
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 9: Run 8 Plot
Run 8 45 Hertz 1.00E+05
PG off
PG on
1.00E+04
1.00E+03 ID#1 0.5 micron per ft3 ID#2 0.5 micron per ft3 1.00E+02
ID#1 5.0 micron per ft3 ID#2 5.0 micron per ft3
1.00E+01
1.00E+00 1
3
5
7
9
11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 Minute
Page 20 of 55
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 10: Run 9 Plot
Run 9 45 Hertz 1.00E+06
PG on
PG off
1.00E+05
1.00E+04
1.00E+03
ID#1 0.5 micron per ft3 ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3
1.00E+02
1.00E+01
ID#2 5.0 micron per ft3
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 10: Run 9 Plot
Run 9 45 Hertz 1.00E+06
PG on
PG off
1.00E+05
1.00E+04
ID#1 0.5 micron per ft3
1.00E+03
ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3 1.00E+02
ID#2 5.0 micron per ft3
1.00E+01
1.00E+00 1
3
5
7
9
11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 Minute
Page 21 of 55
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 11: Run 10 Plot
Run 10 60 Hertz 1.00E+06
PG on
PG off
1.00E+05
1.00E+04
1.00E+03
ID#1 0.5 micron per ft3 ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3
1.00E+02
1.00E+01
ID#2 5.0 micron per ft3
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 11: Run 10 Plot
Run 10 60 Hertz 1.00E+06
PG off
PG on
1.00E+05
1.00E+04
ID#1 0.5 micron per ft3
1.00E+03
ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3 1.00E+02
ID#2 5.0 micron per ft3
1.00E+01
1.00E+00 1
3
5
7
9
11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 Minute
Page 22 of 55
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 12: Run 11 Plot
Run 11 30 Hertz 1.00E+06
PG on
PG off
1.00E+05
1.00E+04
1.00E+03
ID#1 0.5 micron per ft3 ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3
1.00E+02
1.00E+01
ID#2 5.0 micron per ft3
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 12: Run 11 Plot
Run 11 30 Hertz 1.00E+06
PG off
PG on
1.00E+05
1.00E+04
ID#1 0.5 micron per ft3
1.00E+03
ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3 1.00E+02
ID#2 5.0 micron per ft3
1.00E+01
1.00E+00 1
3
5
7
9
11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 Minute
Note: The particle counter (ID#1) ran out of paper at minute 41.
Page 23 of 55
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 13: Run 12 Plot
Run 12 15 Hertz 1.00E+06 PG on
PG off
1.00E+05
1.00E+04
1.00E+03
ID#1 0.5 micron per ft3 ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3
1.00E+02
1.00E+01
ID#2 5.0 micron per ft3
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 13: Run 12 Plot
Run 12 15 Hertz 1.00E+06
PG off
PG on
1.00E+05
1.00E+04
ID#1 0.5 micron per ft3
1.00E+03
ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3 1.00E+02
ID#2 5.0 micron per ft3
1.00E+01
1.00E+00 1
3
5
7
9
11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 Minute
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 14: Run 13 Plot
Run 13 30 Hertz 1.00E+06
PG on
PG off
1.00E+05
1.00E+04
1.00E+03
ID#1 0.5 micron per ft3 ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3
1.00E+02
1.00E+01
ID#2 5.0 micron per ft3
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 14: Run 13 Plot
Run 13 30 Hertz 1.00E+06
PG on
PG off
1.00E+05
1.00E+04
ID#1 0.5 micron per ft3
1.00E+03
ID#2 0.5 micron per ft3 ID#1 5.0 micron per ft3 1.00E+02
ID#2 5.0 micron per ft3
1.00E+01
1.00E+00 1
3
5
7
9
11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 Minute
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Results 2
Figure 15 compares ASD setting to the air change rate. The R fit of 0.999 is an indication of the repeatability of the ASD settings to supply air flow. See Appendix A 3 for statistical analysis. The linear relationship is predicted by the Fan Laws .
Figure 15: Air Change Rate versus ASD Setting and Run
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Results 2
Figure 15 compares ASD setting to the air change rate. The R fit of 0.999 is an indication of the repeatability of the ASD settings to supply air flow. See Appendix A 3 for statistical analysis. The linear relationship is predicted by the Fan Laws .
Figure 15: Air Change Rate versus ASD Setting and Run
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Table C examines the average particle generation rates. For the three runs at each ASD setting and for each particle counter location (ID#), the average and standard deviation are calculated. The high standard deviation relative to the mean is an indication of the high particle generation rate variability. Run 11 is excluded.
Table C: ASD Setting Particle Count Average and Standard Deviation standard
standard
ASDsetting ID# Run# PGRavg average deviation ID# PGRavg average deviation 60
1
1
60
1
7 114.6E+6
2 139.5E+6
60
1
10 149.4E+6
2 186.5E+6
45
1
3 438.6E+6 185.8E+6
45
1
8
22.7E+6
2 105.0E+6
45
1
9
95.9E+6
2 716.3E+6
30
1
4 309.1E+6 134.0E+6
30
1
6
67.9E+6
2 546.2E+6
30
1
13
25.0E+6
2 732.4E+6
15
1
2
15
1
5 538.4E+6
15
1
12
88.6E+6 117.5E+6
40.8E+6 196.7E+6
10.8E+6
30.5E+6
222.0E+6
153.1E+6
296.3E+6
2 105.1E+6 143.7E+6
2 280.5E+6 367.3E+6
2
2
1.0E+9 762.2E+6
35.8E+6 284.4E+6
40.9E+6
314.8E+6
232.3E+6
292.7E+6
2 607.0E+6 2 210.4E+6
Figure 16 compares the average particle concentration in particle per cubic feet to the air change rate in changes per hour. C1avg is the average particle concentration for particle counter ID#1 and C2avg is the average particle concentration for particle counter ID#2. Run 11 is excluded. Figure 17 plots maximum 0.5 micron particle concentration for both particle counter locations by ASD setting. Figure 18 plots average 0.5 micron particle concentration for both particle counter locations by ASD setting. Examining these figures, the test with the ASD at 15 Hertz is much different than the other tests. At an ASD setting of 30 Hertz, the two instruments are much different, but not at ASD settings of 45 Hertz and 60 Hertz. Figure 19 plots maximum 0.5 micron particle concentration for both particle counter locations by run. Figure 20 plots average 0.5 micron particle concentration for both particle counter locations by run. In both figures, there are three points that are high and “don’t fit”. The maximum and average particle concentrations increased over the testing period. For the average particle concentration, instrument 2 had an increase in concentration over the testing period. There is a clear difference in the instruments.
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Figure 16: Average Particle Concentration versus Air Change Rate
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Figure 17: Maximum Particle Concentration Variability Chart
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 17: Maximum Particle Concentration Variability Chart
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Figure 18: Average Particle Concentration Variability Chart
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 18: Average Particle Concentration Variability Chart
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Figure 19: Maximum Particle Concentration by Run
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 19: Maximum Particle Concentration by Run
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Figure 20: Average Particle Concentration by Run
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 20: Average Particle Concentration by Run
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Table D shows the actual two log reduction room recovery rates for both pa rticle counter locations. This information is sorted by ASD setting and run number. The average and standard deviation of the three runs at each ASD setting for each particle counter location is shown (see Appendix A for JMP output). The low standard deviation is an indication of high repeatability of this test. The higher standard deviation at ASD setting of 15 Hertz indicates that the test is not as repeatable at lower air change rates. Run 11 is excluded.
Table D: Two Log Reduction Recovery Rate Averages and Standard Deviations Run #
ASD
ASD
N air
R1act actual 2
R2act actual 2
change
log
log
rate in
recovery
recovery
setting in changes Hz
time in
per hour minutes
standard
time in
average deviation minutes
standard average deviation
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Table D shows the actual two log reduction room recovery rates for both pa rticle counter locations. This information is sorted by ASD setting and run number. The average and standard deviation of the three runs at each ASD setting for each particle counter location is shown (see Appendix A for JMP output). The low standard deviation is an indication of high repeatability of this test. The higher standard deviation at ASD setting of 15 Hertz indicates that the test is not as repeatable at lower air change rates. Run 11 is excluded.
Table D: Two Log Reduction Recovery Rate Averages and Standard Deviations Run #
ASD
ASD
N air
R1act actual 2
R2act actual 2
change
log
log
rate in
recovery
recovery
setting in changes Hz
time in
standard
per hour minutes
time in
standard
average deviation minutes
1
60
49.0
9
8.7
7
60
46.5
9
9
10
60
47.7
8
8
3
45
34.6
11
8
45
33.5
11
11
9
45
34.3
9
9
4
30
20.4
14
6
30
20.3
13
12
13
30
20.7
14
13
2
15
7.1
36
5
15
6.9
26
22
12
15
7.5
34
26
10.3
13.7
32.0
0.6
1.2
0.6
5.3
9
11
13
30
average deviation 8.7
0.6
10.3
1.2
12.7
0.6
26.0
4.0
Figure 21 compares the actual and theoretical two log recovery times in minutes to the ASD setting in Hertz. R1act is the actual two log recovery time for particle counter location ID#1. R1th is the theoretical two log recovery time for particle co unter location ID#1. R2act is the actual two log recovery time for particle counter location ID#2. R2th is the theoretical two log recovery time for particle counter location ID#2. Run 11 is excluded. Figure 22 compares the difference between actual and theoretical two log recovery times by ASD setting. Figure 23 compares the difference between actual and theoretical two log recovery time by run. The air change rate is significant. Only for the ASD settings of 30 Hertz are the results near zero, yet the instruments are different. For the ASD settings of 45 and 60 Hertz, the difference is consistent but actual is greater than theoretical. For the ASD setting of 15 Hertz, all the results are less than theoretical.
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Figure 21: Two Log Recovery Time versus ASD Setting
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Figure 22: Difference between Actual and Theoretical 2 Log Recovery by ASD Setting
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 22: Difference between Actual and Theoretical 2 Log Recovery by ASD Setting
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 23: Difference Between Actual and Theoretical 2 Log Recovery by Run
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Figure 23: Difference Between Actual and Theoretical 2 Log Recovery by Run
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Discussion There was a delay in the particle generator starting during some runs. This is apparent in the following Figures and Runs. • Figure 3, Run 2 • Figure 4, Run 3 • Figure 5, Run 4 • Figure 6, Run 5 • Figure 9, Run 8 • Figure 10, Run 9 • Figure 12, Run 11 • Figure 13, Run 12 During some runs, the particle generation dec lined prior to turning off the particle generator. This is apparent in the following Figures and Runs. • Figure 5, Run 4
Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Discussion There was a delay in the particle generator starting during some runs. This is apparent in the following Figures and Runs. • Figure 3, Run 2 • Figure 4, Run 3 • Figure 5, Run 4 • Figure 6, Run 5 • Figure 9, Run 8 • Figure 10, Run 9 • Figure 12, Run 11 • Figure 13, Run 12 During some runs, the particle generation dec lined prior to turning off the particle generator. This is apparent in the following Figures and Runs. • Figure 5, Run 4 • Figure 6, Run 5 • Figure 7, Run 6 • Figure 10, Run 9 • Figure 12, Run 11 • Figure 14, Run 13 During some runs, the particle generation co ntinued after the particle generator (PG) was turned off. This is apparent in the following Figures and Runs. • Figure 2, Run 1 • Figure 3, Run 2 • Figure 4, Run 3 • Figure 8, Run 7 • Figure 9, Run 8 • Figure 11, Run 10 The inconsistent particle generation may be attributable to: • Unstable aerosol production by the Laskin nozzles at 3 psig. • Aerosol back pressure building up upstream of the diaphragm valve and then bleeding off after the generator was turned off. • Variation in the room absolute pressure due to varying air supply flow rate which creates varying backpressure on the aerosol generator hose discharge. The unstable aerosol production may be due the flow surging because the nozzle did not reach sonic velocity, also known as choked flow. The 5 micron particles were significantly higher in concentration at lower airflow rates. This is expected since higher airflow rates have a higher transport velocity and carries larger particles more easily.
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For plotting on semi-log scale, particle counts of zero were rounded up to one. For the 0.5 micron data, particle counts of less than 10 can be ignored since dilutors with a 10:1 ratio were installed on the particle counters. The particle counts at locations ID#1 and ID#2 were notably separated in the following Figures and Runs. • Figure 5, Run 4 (30Hz) • Figure 9, Run 8 (45 Hz) • Figure 12, Run 11 (30Hz) • Figure 13, Run 12 (15 Hz) • Figure 14, Run 13 (30 Hz) The particle concentration difference in the two instruments is also indicated in Figures 16 and 17. There is more separation between instruments at an ASD setting of 30 Hertz than other settings. Significantly different airflow patterns between higher and lower air flow rates may account for this separation. Computational Fluid Dynamic (CFD) computer models may be a useful tool to determine if this is the case. Figure 20 also indicates that the separation between instruments became greater over time, specifically runs 11-13. Figure 22 shows a difference in the instruments at an ASD setting of 30 Hertz. Table D and Figures 21 and 22 show that the room recovery rates are consistent between runs at the same ASD settings of 30, 45, and 60 Hertz. This indicates that this test is a good measure of the room recovery rate. This is also indicated by the low standard deviations in Table D. The room recovery rate was inconsistent at the ASD setting of 15 Hertz. Sources for error include: • Shortridge AirData Multimeter calibration • Supply air flow rate measurement technique • Particle counter calibration • Dilutor calibration • HEPA filter integrity (Supply air particle counts) • Room pressurization variability between cartridge prep room and a djacent rooms. • Room pressurization variability, the effect of the room absolute pressure on the aerosol generator • Repeatability of the particle generation rate • Not deducting equipment volume from the room volume calculations
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Conclusions For this application, the room recovery rate test is a good measure of cleanroom performance. The theoretical equation provided good estimates of the actual performance. However, at an ASD setting of 15 Hz (seven air changes per hour), the theoretical equation provided poor estimates of the actual performance.
A more consistent method of generating particles is needed for future testing. The particle generation needs to begin immediately when the particle generator is started. The particle generation rate needs to be consistent from minute to minute when the particle generator is operating. The particle generation needs to end when the particle generator is stopped. The generation rate needs to be independently determined or measured instead of using the equation based on supply air volume used in this report.
References 1. ISPE Good Practice Guide Heating, Ventilation, and Air Conditioning, First Edition, International Society of Pharmaceutical Engineers (ISPE), 2009, p. 253 2. DiGiovanni, M and Spearman T, “Recovery Testing a Pharmaceutical Cleanroom Case Study”, Performance Review, Spring 2006 edition, Controlled Environment Testing Association (CETA), p. 7-14. 3. 2008 ASHRAE Handbook – HVAC Systems and Equipment , page 20.4.
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Appendix A Statistical Analysis JMP 7.01 was used for all analyses. The ASD setting and the air change rate is the same for both ID# 1 and 2. This regression analysis uses ID#1 and includes Run #11.
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
This table was generated using Tables Summary. ASD set ti ng i n Hertz
ID#
N Rows
Mean(actual 2 log recovery time in minutes)
Std Dev(actual 2 lo g recovery time in minutes)
15
1
3
32
5.29150262
15
2
3
26
4
30
1
3
13.6666667
0.57735027
30
2
3
12.6666667
0.57735027
45
1
3
10.3333333
1.15470054
45
2
3
10.3333333
1.15470054
60
1
3
8.66666667
0.57735027
60
2
3
8.66666667
0.57735027
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Appendix B Photographs
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Photo B1: Particle Counter with Dilutor
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Photo B2: Particle Counter with Dilutor
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Photo B3: Low Level Vent
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Photo B4: Low Level Vent
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Photo B5: Aerosol Generator Diaphragm Valve and Hose
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Photo B6: Aerosol Generator
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Pharmaceutical Cleanroom HVAC Ventilation Rate Study
Photo B7: Vail Washer Protected with Plastic
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Photo B8: Aerosol Generator Diaphragm Valve
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Photo B9: Aerosol Generator Diaphragm Valve
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Photo B10: Cartridge Washer
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Photo B11: Sterilization Tunnel
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Photo B12: Sterilization Tunnel
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