Equipment Qualification Considerations When Purchasing, Designing,
or Qualifying Storage Units
Robert Craig MillerSenior Validation SpecialistVaLogic, LLC
Purpose of Today’s Meeting
• Discuss the regulatory requirements driving our processes and the relationship to test scripts.
• Discoveries encountered in Validations.
• Q & A
Receipt Storage Distribution
Shipper Qualification Temperature Monitoring Shipper Qualification
Equipment Certification Preventive Maintenance Document Control
Equipment Qualification Equipment Certification
Document Control Change Control
Equipment Qualification
Document Control
Cradle To Grave
Definitions• Acceptance Criteria – The standards a product or process must meet to
successfully complete a test phase or to meet delivery requirements.
• As-Found-Data – Data comparing the response of an instrument to known standards, as determined without adjustment, after the instrument is made operational.
• Calibration: The process of adjusting an instrument or compiling a deviation chart so that its reading can be correlated to the actual value being measured.
• Certification – A documented statement, by authorized and qualified individuals, that an equipment/system validation, revalidation, qualification, re-qualification, or calibration has been performed appropriately with acceptable results.
• Change Control – A formal monitoring system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect a validated status.
Definitions (Continued)• Corrective Action – An action, specified in Standard Operating Procedures, that is
taken in response to information gathered from environmental monitoring data. This may be implemented when Alert or Action Limits are exceeded or when Trend Analysis indicates a developing problem.
• Critical – Of or pertaining to a condition causing an abrupt change in the quality or property of an environment, process or product.
• Critical Component – Any component of a critical device that’s failure to perform can be reasonably expected to cause the failure of a critical device, or to affect the device’s safety or effectiveness.
• Critical Instrumentation – Those instruments which are pertinent to the proper operation, control, and recording of critical process parameters.
• Critical Process Parameter – A control parameter that has a direct relationship to the quality, safety, effectiveness, or performance of the intermediate or final product.
Definitions (Continued)• Final Report – A document summarizing the results derived from the execution of a
protocol. The final report shall include a conclusion, which indicates validation success or failure and designates proven acceptable ranges for all critical process parameters as determined by the execution of the validation protocol.
• Installation Qualification – The performance of documented verification that an equipment/system installation adheres to approved contract specification and achieves design criteria.
• Operational Qualification – The documented verification that the equipment/system performs per design criteria over all defined operating ranges.
• Performance Qualification – Documented verification that equipment, systems, or processes operate the way they are purported to do. This operation must be reliable and reproducible within a specified, predetermined set of parameters under normal production conditions and must be in a state of control.
Definitions (Continued)• Protocol – The written and approved document of an experimental sequence of tests that, when
executed as prescribed, are intended to produce documented evidence that the equipment or system does what it is designed or claims to do reproducibly.
• Qualification – Operation aimed at proving, with regard to materials, equipment, or personnel, that the required conditions are met and that they actually provide the expected results.
• Trend Analysis – Periodic review and analysis of environmental monitoring program results that can be related to time, shift, facility, etc. for patterns that may suggest underlying or developing problems.
• Validation – The overall term for establishing documented evidence through defined tests and challenges, that a system, manufacturing process, analytical method, and/or piece of equipment meets design criteria and that adequate provisions have been established to keep it in a state of control so it will produce a product that meets predetermined specifications and quality attributes. Validation can be performed prospectively, concurrently, or retrospectively.
• Validation Master Plan – The establishment of a dynamic written plan that defines the overall approach to a validation project.
So . . . what is Validation?
• Legal responsibility?• Ethical responsibility?• Sound Business Practice?
Regulatory Requirements Validation and Documentation
The FDA’s 1987 guideline defines validation as:
• Establishing documented evidence, which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality characteristics.
Key Validation Documents
• Validation Master Plan (VMP)
• User Requirements
• Functional Specifications
• Validation Protocols
• Standard Operating Procedures (SOPs)
• Validation Final Reports
• Change Control System
User Requirements
• Can you identify your needs– In writing?
• Musts vs. Wants
• Simple, yet has a large impact on the design and validation processes
• Provides basis for PQ acceptance criteria
Functional Specifications
• The “How To’s” of meeting the User Requirements
• Other Terms– User Requirement Specification– Purchasing Specification– Technical Specification
• Provides basis for OQ and PQ acceptance criteria
Detailed Design
• The hard specifics of the design
• Detailed specifications and drawings– Cut sheets– Technical specs– P&ID’s– Manufacturer’s documentation
• Provides the basis for IQ
Design / Validation Relationship
User Requirements PQ
Functional Spec OQ
Detailed Design IQ
Build
Typical Things Done – Summary Reports
• Completed following protocol execution– Following completion of each protocol– May “lump” IQ / OQ together
• Content– Defined by Validation Master Plan / SOPs– Clearly states whether equipment met acceptance criteria as
stated in the approved protocols– Clearly states user limitations on the equipment, if any– Provides raw data obtained during the studies, along with
information regarding performance of the unit during the studies, for example:• How long the unit maintained acceptable temperatures following
power loss?• Hot and Cold spots in the unit
GMP Relevance & Risk AssessmentSection
21 CFR Relevance
Product Equipment Section21 CFR
RelevanceProduct Equipment
Installation Qualification Performance Qualification
Purchase Order Verification 211.63N/A Moderate
Operational Qualification Verification
211.22, 211.63, and 211.100
High Low
Manufacturer’s. Documentation Verification
211.67, 211.68, and 211.100 N/A Moderate
Equipment Set-up and Thermocouple Placement Verification
211.68 and 211.100 Low Low
Environmental Conformance Verification
211.63N/A High
Operating Temperature Thermal Mapping
211.63, 211.68,
211.100, and 211.142
High N/A
Electrical Utilities Verification Same as aboveN/A High
Thermocouple Calibration Verification
211.68 and 211.100 Low N/A
Standard Operating Procedure Verification
211.67, 211.68,
211.100, and 211.142
N/A ModerateValidation Test Equipment Verification
211.68Low Moderate
Operational Qualification Re-qualification
Installation Qualification Verification
211.22, 211.63, and 211.100
Low ModeratePreventive Maintenance Verification 211.67, 211.68,
and 211.100Low High
Validation Test Equipment Verification
211.68Low Moderate
Critical Instrumentation Calibration/Certification Verification
211.68 and 211.100 High Low
Critical Instrumentation Calibration/Certification Verification
211.68 and 211.100 High Low
Electrical Utilities Verification 211.63N/A High
Equipment Set-up and Thermocouple Calibration
Same as aboveModerate N/A
Validation Test Equipment Verification
211.68Moderate N/A
Temperature Distribution Thermal Mapping
211.63, 211.68,
211.100, and 211.142
High N/AEquipment Set-up and Thermocouple Calibration
211.68 and 211.100 Moderate N/A
Open Door Analysis Thermal Mapping
Same as aboveModerate N/A
Operating Temperature Thermal Mapping
211.63, 211.68,
211.100, and 211.142
High N/A
Power Failure Analysis Thermal Mapping
Same as aboveModerate N/A
Thermocouple Calibration Verification
211.68 and 211.100
Moderate N/A
Alarms and Controls Testing 211.68, 211.100, and 211.142
High LowAlarms and Controls Testing 211.68, 211.100,
and 211.142High Low
Re-qualification
• Event Driven– Replacement of
critical components – Change in process or
procedures– Change in personnel– Failure Investigation
• Time Driven– Change of “the little
things” over time– Poorly maintained
systems– Routine system
failure– Environment
dependent
Change Control
• The modification, relocation or decommissioning of any equipment that has been tested under validation conditions must be documented.
• Change Control is necessary to perpetuate validation
• When should Change Control begin?– After the validation report is approved?– Before qualification begins?
Difficulties in Validation
• Inadequate definition of system requirements / specifications
• Poor protocols
• Inadequate resolution / explanation of failures / deviations
• Poor planning
• Poor communication
Success in Validation
• Getting Validation personnel involved early in the process
• Well defined user requirements and specifications
• Good Communication
• Integrating Validation into design-build-test-use cycle
Discoveries
• What we have learned in our supporting role to Operations.– Identifying hot and cold spots.– Affects of TC placement on loaded upright,
ultra-low storage unit.– Same is often different.– Hidden costs of being economical.– Helping is sometimes hurting.– When up is down and when down is up.
Typical TC Placement Diagram
TC 01
TC 02
TC 06
TC 04
TC 05
TC 07
TC 08
TC 09
TC 10
TC 11
TC 12
TC 03
TC Shelf Location Suspension
01 Top Back Left Liquid
02 Top Front Right Airborne
03 Second Front Left Airborne
04 Second Controller Airborne
05 Third Back Left Airborne
06 Third Center Airborne
07 Third Front Right Airborne
08 Fourth Front Left Airborne
09 Fourth Back Right Airborne
10 Bottom Center Liquid
11 Bottom Front Right Airborne
12 External Filter Airborne
Probe Placement on a Walk-in
FRONT OF UNIT
RTD
8.8'
8.5'
7.4'
Probe 01Back
Back
Back
Front
Front
Front
Back
Middle
Probe 02Front
Probe 03Middle
Probe 04
Probe 05
Probe 11
Probe 06
Probe 07
Probe 09
Probe 10
High Level6' from floor
Mid Level4' from floor
Low Level2' from floor
MiddleProbe 08
MiddleProbe 12
Affects Upon Temperature During TC Placement
-100
-90
-80
-70
-60
-50
-40
-30
-20
-10
0
10
20
30
40
11:42:40
12:20:00
13:00:00
13:40:00
14:20:00
15:00:00
15:40:00
16:20:00
17:00:00
17:40:00
18:20:00
19:00:00
19:40:00
20:20:00
21:00:00
21:40:00
22:20:00
23:00:00
23:40:00
0:20:00
1:00:00
1:40:00
2:20:00
3:00:00
3:40:00
4:20:00
5:00:00
5:40:00
6:20:00
7:00:00
7:40:00
8:20:00
9:00:00
9:40:00
10:20:00
11:00:00
11:40:00
Time
Tem
per
atu
re
201A-T13 202A-T14 203A-T15 204A-T16 205A-T17 206A-T18
207A-T19 208A-T20 209A-T21 210A-T22 211A-T23 Ambient
TC placement
Temperatures below -70C
Undocumented entry by Operations
-100
-90
-80
-70
-60
-50
-40
-30
-20
-10
0
10
20
30
40
11:42:40
12:20:00
13:00:00
13:40:00
14:20:00
15:00:00
15:40:00
16:20:00
17:00:00
17:40:00
18:20:00
19:00:00
19:40:00
20:20:00
21:00:00
21:40:00
22:20:00
23:00:00
23:40:00
0:20:00
1:00:00
1:40:00
2:20:00
3:00:00
3:40:00
4:20:00
5:00:00
5:40:00
6:20:00
7:00:00
7:40:00
8:20:00
9:00:00
9:40:00
10:20:00
11:00:00
11:40:00
Time
Tem
per
atu
re
101A-T01 102A-T02 103A-T03 104A-T04 105A-T05 106A-T06
107A-T07 108A-T08 109A-T09 110A-T10 111A-T11 Ambient
TC placement
Temperatures below -70C
• Same model; same set point; same TC diagram.• Different load; different age; different ambient.• Recovery time: 8 hours and 16 hours, respectively.
All units of same model are created equal; some operate more efficiently
than others.
-90
-88
-86
-84
-82
-80
-78
-76
-74
-72
-70
-68
-66
12:16:05
12:55:00
13:35:00
14:15:00
14:55:00
15:35:00
16:15:00
16:55:00
17:35:00
18:15:00
18:55:00
19:35:00
20:15:00
20:55:00
21:35:00
22:15:00
22:55:00
23:35:00
0:15:00
0:55:00
1:35:00
2:15:00
2:55:00
3:35:00
4:15:00
4:55:00
5:35:00
6:15:00
6:55:00
7:35:00
8:15:00
8:55:00
9:35:00
10:15:00
10:55:00
11:35:00
12:15:00
Tim e
Tem
p
TC 01 TC 02 TC 03 TC 04 TC 05 TC 06 TC 07 TC 08 TC 09 TC 10 TC 11
-90
-88
-86
-84
-82
-80
-78
-76
-74
-72
-70
-68
-66
12:16:05
12:55:00
13:35:00
14:15:00
14:55:00
15:35:00
16:15:00
16:55:00
17:35:00
18:15:00
18:55:00
19:35:00
20:15:00
20:55:00
21:35:00
22:15:00
22:55:00
23:35:00
0:15:00
0:55:00
1:35:00
2:15:00
2:55:00
3:35:00
4:15:00
4:55:00
5:35:00
6:15:00
6:55:00
7:35:00
8:15:00
8:55:00
9:35:00
10:15:00
10:55:00
11:35:00
12:15:00
Tim e
Tem
p
TC 01 TC 02 TC 03 TC 04 TC 05 TC 06 TC 07 TC 08 TC 09 TC 10 TC 11
-90
-88
-86
-84
-82
-80
-78
-76
-74
-72
-70
-68
-66
12:16:05
12:55:00
13:35:00
14:15:00
14:55:00
15:35:00
16:15:00
16:55:00
17:35:00
18:15:00
18:55:00
19:35:00
20:15:00
20:55:00
21:35:00
22:15:00
22:55:00
23:35:00
0:15:00
0:55:00
1:35:00
2:15:00
2:55:00
3:35:00
4:15:00
4:55:00
5:35:00
6:15:00
6:55:00
7:35:00
8:15:00
8:55:00
9:35:00
10:15:00
10:55:00
11:35:00
12:15:00
Tim e
Tem
p
TC 01 TC 02 TC 03 TC 04 TC 05 TC 06 TC 07 TC 08 TC 09 TC 10 TC 11
-90
-88
-86
-84
-82
-80
-78
-76
-74
-72
-70
-68
-66
14:56:15
15:30:00
16:05:00
16:40:00
17:15:00
17:50:00
18:25:00
19:00:00
19:35:00
20:10:00
20:45:00
21:20:00
21:55:00
22:30:00
23:05:00
23:40:00
0:15:00
0:50:00
1:25:00
2:00:00
2:35:00
3:10:00
3:45:00
4:20:00
4:55:00
5:30:00
6:05:00
6:40:00
7:15:00
7:50:00
8:25:00
9:00:00
9:35:00
10:10:00
10:45:00
11:20:00
Tim e
Tem
p
TC 01 TC 02 TC 03 TC 04 TC 05 TC 06 TC 07 TC 08 TC 09 TC 10 TC 11
Cost of Quality Acceptance Criteria: -195°C to -135°C
Slot Brand X - Economical Brand Y – Top of the Line
1 -88.5°C -178.6°C
2 -94.5°C -182.1°C
3 -118.3°C -186.4°C
4 -127.0°C -187.8°C
5 -154.9°C -188.8°C
6 -159.5°C -189.8°C
7 -171.1°C -190.9°C
8 -187.9°C -192.2°C
9 -192.2°C -192.6°C
10 -194.6°C -192.8°C
11 -194.8°C -193.5°C
12 -196.5°C -194.1°C
13 -196.6°C -194.3°C
Quick “Fix” Acceptance Criteria: -195°C to -135°C
Slot Temperature – High Fill Set Point of 7” Temperature – High Fill Set Point of 10”
1 -88.5°C -125.3°C
2 -94.5°C -134.7°C
3 -118.3°C -139.3°C
4 -127.0°C -149.2°C
5 -154.9°C -153.4°C
6 -159.5°C -160.9°C
7 -171.1°C -167.5°C
8 -187.9°C -184.3°C
9 -192.2°C -192.1°C
10 -194.6°C -196.8°C
11 -194.8°C -196.9°C
12 -196.5°C -196.9°C
13 -196.6°C -197.1°C
Criticality of Temperature Set Point
Temperature Control Set Point at -85.0C
-90
-88
-86
-84
-82
-80
-78
-76
-74
-72
-70
-68
-66
-64
-62
-60
12:50:00
12:55:00
13:00:00
13:05:00
13:10:00
13:15:00
13:20:00
13:25:00
13:30:00
13:35:00
13:40:00
13:45:00
13:50:00
13:55:00
14:00:00
14:05:00
14:10:00
14:15:00
14:20:00
14:25:00
14:30:00
14:35:00
14:40:00
14:45:00
14:50:00
14:55:00
15:00:00
15:05:00
15:10:00
15:15:00
Time
Tem
per
atu
re (
Deg
C)
Min Max Avg
Temperature Control Set Point at -80.0C
-90
-88
-86
-84
-82
-80
-78
-76
-74
-72
-70
-68
-66
-64
-62
-60
12:50:00
12:55:00
13:00:00
13:05:00
13:10:00
13:15:00
13:20:00
13:25:00
13:30:00
13:35:00
13:40:00
13:45:00
13:50:00
13:55:00
14:00:00
14:05:00
14:10:00
14:15:00
14:20:00
14:25:00
14:30:00
14:35:00
14:40:00
14:45:00
14:50:00
14:55:00
15:00:00
15:05:00
15:10:00
15:15:00
Time
Tem
per
atu
re (
Deg
C)
Min Max Avg
Affects of Dynamic Testing
-2
-1
0
1
2
3
4
5
6
7
8
9
10
11
11
:00
:00
12
:10
:00
13
:20
:00
14
:30
:00
15
:40
:00
16
:50
:00
18
:00
:00
19
:10
:00
20
:20
:00
21
:30
:00
22
:40
:00
23
:50
:00
01
:00
:00
02
:10
:00
03
:20
:00
04
:30
:00
05
:40
:00
06
:50
:00
08
:00
:00
09
:10
:00
10
:20
:00
11
:30
:00
12
:40
:00
13
:50
:00
15
:00
:00
16
:10
:00
17
:20
:00
18
:30
:00
19
:40
:00
20
:50
:00
22
:00
:00
23
:10
:00
00
:20
:00
01
:30
:00
02
:40
:00
03
:50
:00
05
:00
:00
06
:10
:00
07
:20
:00
08
:30
:00
09
:40
:00
10
:50
:00
Time
Te
mp
era
ture
(D
eg
C)
B090 B131 B135 B145 B277 B353 B354 B403 D002 D003 D685 D686
D687 D691 D692 D693 D694 D695 D697 D698 D699 D700 D701 D703
D704 D705 D706 D707 D709 D710 D711 D712 D713 D714 D721 D722
Open Door Test #1
Open Door Test #2 Open Door Test #3
To Summarize
• As the User, know your requirements and processes.
• Validation is a lifecycle approach. It’s not a one and done.
• Be cognizant of change control.• Have a thorough TC/logger placement diagram to
detect hot and cold spots.• Understand the functionality of the units being
qualified.• But, above all, the most import thing to remember
is that . . .
OUR PRIMARY OBLIGATION IS TO THE END USER
• Family• Friends• Co-workers• Strangers
Thank You For Your Participation
Questions, comments, complaints?
About the Presenter
Robert “Craig” Miller has over twenty years experience working in the pharmaceutical and biotech support industry. Starting off as a Repository Technician at the National Cancer Institute Clinical Repository, he has held increasing key positions and recently left Fisher BioServices (formerly McKesson BioServices, Ogden BioServices) after ten years as the Validation Manager to join VaLogic, LLC, a calibration and validation consulting firm supporting life sciences.
Contact Information:
Email: [email protected]
Office: 240-529-1673
Cell: 240-602-1424
Fax: 240-529-1678
Web: www.valogic.us