Professional Documents
Culture Documents
Elements to Consider
When Qualifying Control
Environmental Chambers Used
for CGMP Applications
David Vincent and Allan Marinelli
Table I: Setup parameters. cycle it is acceptable that the temperature (i.e., ther-
Type of study Temperature distribution mocouples measured in air) to go slightly out of
2C or 8C for a very short period of time. When
Number of thermocouples 16 total
the defrost cycle temperature fluctuation occurs it
Type of thermocouple T
is recommended to perform an additional study
Resolution 0.01C by encompassing the geometric placement of the
Validator hardware thermocouples in product or solution in support
Printer intervals N/A of this protocol and to subsequently ensure that the
PCMCIA intervals N/A 2C to 8C are met.
File intervals 10 min
OPEN-DOOR STUDY
This test is done to measure the time that it takes for the
temperature controlling unit to recover from temperature
Table II: Kaye calibration points requirements. fluctuation caused by opening the door.
Low -5C An open-door study can be useful in explaining how
the product can be affected or not affected to an auditor
High 15C
by the constant opening and closing of the door during
Check 4C a typical work schedule. To fully capture the range of
Sensor stability criteria the opening door data, four phases must be tested as
Maximum temperature change 0.5C follows:
Duration 3 minutes Priorto-open-door phase
Open door phase
Sensor deviation criteria
Close door phase
Maximum uncalibrated deviation from standard 1.0C Normal phase.
Maximum calibrated deviation from standard 0.5C
Log corrected results at 30-second intervals for 3 minutes This test is performed in an empty chamber distribu-
tion profiling X amount of hours or the minimum time
required to attain all four phases in condition that at
Data Analysis least one hour in each of the priorto-open-door phase
The following steps should be performed for data and normal phase is attained.
analysis:
Record any thermocouples that are outside the 2C Procedure
to 8C operating range and the duration they are An example of a generic open-door study procedure is
out during defrost cycle indicated as follows:
Graph the data and interpret the results per SOP Prepare and calibrate 16 thermocouples using the
XXXX setup parameters specified in Table III. The pre-cali-
Verify that no more than 10% of the thermocouples bration of all thermocouples must Pass the pre-
malfunctioned during the study or failed post-study defined specifications as stipulated in Table IV. For
verification. operation of the Kaye 2000, refer to the Kaye Valida-
tor 2000 operation manual and/or SOP XXXXXX.
Acceptance Criteria Distribute 16 calibrated thermocouples throughout
The following criteria should be obtained: the interior of the cold room in accordance with
Calibration verification readings (post-calibration Figure 1
of thermocouples) must be within 0.5C of the Allow the temperature in the chamber to stabilize
reference temperature standard. More than 85% of at set point
all thermocouples must be within 0.5C during Initiate data logging and ensure data are captured in
post-use calibration verification. each of the identified phases specified as follows:
The temperature in every location during empty Prior to open door phase
chamber distribution must be controlled within Open door phase
2C to 8C. Attach all supporting data such as Close door phase
excel graphs, etc. (see Figure 2). During every defrost Normal phase.
88 Journal of Validation T echnology [Spring 2009] iv thome.com
D AV I D V I N C E N T A N D A L L A N M A R I N E L L I
8.00
TC 01
TC 02
7.00
TC 03
TC 04
Temperature ( C)
6.00 TC 05
TC 06
5.00 TC 07
TC 08
TC 09
4.00 TC 10
TC 11
3.00 TC 12
TC 13
TC 14
2.00 TC 15
TC 16
1.00
0.00
13:26:22
14:59:00
16:32:00
18:05:00
19:38:00
21:11:00
22:44:00
11:08:00
12:41:00
14:14:00
15:47:00
17:20:00
18:53:00
20:26:00
21:59:00
23:32:00
10:23:00
11:56:00
13:29:00
15:02:00
0:17:00
1:50:00
3:23:00
4:56:00
6:29:00
8:02:00
9:35:00
1:05:00
2:38:00
4:11:00
5:44:00
7:17:00
8:50:00
Time
Acceptance Criteria
The following criteria should be obtained:
Calibration verification readings (post-calibra- Table IV: Kaye calibration points requirements.
tion of thermocouples) must be within 0.5C Low -5C
of the reference temperature standard. More than
High 15C
85% of all thermocouples must be within 0.5C
Check 4C
during post-use calibration verification.
A ll four phases are captured as specified in the Sensor stability criteria
procedure section. Attach all supporting data Maximum temperature change 0.5C
such as Excel graphs. For example, refer to Fig- Duration 3 minutes
ure 3. Note: The door was opened for a longer
Sensor deviation criteria
duration on the left side of Figure 3 compared
Maximum uncalibrated deviation from standard 1.0C
to the right side (the second time the door was
opened). Maximum calibrated deviation from standard 0.5C
Log corrected results at 30-second intervals for 30 seconds
12.00
10.00
Temperature ( C)
8.00
TC 04
TC 12
TC 14
6.00 TC 16
4.00
2.00
0.00
10:32:01
13:03:30
11:22:30
14:44:30
12:13:00
13:54:00
21:28:30
0:00:00
0:50:30
1:41:00
2:31:30
3:22:00
4:12:30
5:03:00
5:53:30
6:44:00
7:34:30
8:25:00
9:15:30
10:56:30
11:47:00
15:35:00
16:25:30
17:16:00
18:06:30
18:57:00
19:47:30
20:38:00
22:19:00
23:09:30
10:06:00
13:28:00
Time 12:37:30
20.00
Temperature ( C)
15.00
TC 04
TC 07
TC 14
TC 16
10.00
5.00
0.00
11:16:17
14:01:00
18:36:00
23:11:00
12:56:00
12:11:00
15:51:00
0:06:00
1:01:00
1:56:00
2:51:00
3:46:00
4:41:00
5:36:00
6:31:00
7:26:00
8:21:00
9:16:00
11:06:00
12:01:00
13:06:00
14:56:00
15:41:00
16:46:00
17:41:00
19:31:00
20:26:00
21:21:00
22:16:00
10:11:00
13:51:00
14:46:00
Time
Following the completion of the power failure tem- reference temperature standard. More than 85% of
perature profile study, perform a post-study verifica- all thermocouples must be within 0.5C during
tion of the thermocouples. post-use calibration verification.
All four phases are captured as specified in the pro-
Data Analysis cedure section. Attach all supporting data such as
The following steps should be performed for data excel graphs (see Figure 4).
analysis: Note: This test is to be used For information only.
Print the Kaye data logger report and the thermo-
couple calibration report. Attach all reports to the FULL-LOADED CHAMBER THERMO-
protocol. PROFILE MAPPING (PQ)
Interpret the results per SOP XXXX. The instruction for the empty chamber test is also
Verify that no more than 10% of the thermocouples applicable to the loaded chamber thermo-profile. The
malfunctioned during the study or failed post-study full-loaded chamber is defined as having at least 80%
verification. of surface area loaded with samples and containers in
order to determine the effects and impact on the prod-
Acceptance Criteria uct. This will ensure both thermo profiling extremes are
The following criteria should be obtained: tested, empty versus loaded conditions. Consequently,
Calibration verification readings (post-calibration a product impact assessment can be conducted and
of thermocouples) must be within 0.5C of the easily rationalized during an audit. Optionally, an
gxpandjv t.com Journal of Validation T echnology [Spring 2009] 91
PEER-R EV IEW ED