Qualification, calibration and maintenance of

stability chambers
Dr. Mathias Kramer
Agenda

1. Qualification of stability chambers

2. Calibration of equipment of stability chambers

3. Maintenance of stability chambers

Qualification

1. Qualification of stability chambers

1.1 General aspects
1.2 URS, analysis of local conditions
1.3 Qualification: DQ, IQ, OQ, PQ
1.4 periodic Re-Qualification
Qualification
general aspects

Qualification = Project management

• define good Team-Members, experts where needed

DQA, Engineer, technician, system owner (teamleader)
Dthe team determines your success

• approach: planning D doing D reporting

• using professional project management Tool (MS-Project)
• define milestones
• arrange periodical status- meetings
Qualification
general aspects

MS-Project-Plan:
Qualification

1. Qualification of stability chambers

1.1 General aspects
1.2 URS, analysis of local conditions
1.3 Qualification: DQ, IQ, OQ, PQ
1.4 periodic Re-Qualification
Qualification
User Requirement Specification

URS: Document to collect all requirements

• define usage very precisely (which kind of samples will be stored?)

• define climatic condition
-nominal value, according ICH Q1A, WHO
(e.g. accelerated conditions: 40°C ± 2°C / 75 % r.H. ± 5 % r.H.)
- limits, according ICH Q1A,
- additional conditions
(e.g. Humidity in 5°C-Cells is not recommended, but very important)
Qualification
User Requirement Specification

URS: Document to collect all requirements

• define location, shape and area needed

• define equipment (shelves, drawer needed?)
• define safety and enviromental aspects (fire detector)
• define security requirements (on-line monitoring, locking system)
• define budget
• define basis and scale of qualification
Qualification
analysis of local conditions

Find the best location (building) for stability chambers

consider
• flow line (Short way, minimal horizontal moving)
• infrastructure (water, air condition, additional deconstruction)
• safety and enviromental aspects (energy saving)
• security requirements (available access control-systems)
Qualification

1. Qualification of stability chambers:

1.1 General aspects
1.2 URS, analysis of local conditions
1.3 Qualification: DQ, IQ, OQ, PQ
1.4 periodic Re-Qualification
Qualification
overview

Qualification of a (new) climatic chamber: 4 Qualification Phases

1.Phase 2.Phase 3.Phase 4.Phase

MQP DQ IQ OQ PQ MQR

DQ: Design Qualification

MQP: Master-Qualification Plan IQ: Installation Qualification
MQR: Master-Qualification Report OQ: Operational Qualification
PQ: Performance Qualification
Qualification
1. Phase: DQ-Design Qualification

Start D need of a climatic chamber

• write and approve DQ-Plan

• getting different tenders
• Check technical manuals
• URS available
• write and approve DQ-Report (with reported open issues) before starting IQ

End D Order of the designed chamber

Qualification
2. Phase: IQ-Installaltion Qualification

Start D delivery of the climatic chamber

• write and approve IQ-Plan

• compare ordered and delivered material
• Installation of the climatic chamber according local requirements / standards
• first function check
• prepare a (technical) logbook
• Installation of additional equipment (monitoring sensor or flash-light)
• write and approve IQ-Report (with reported open issues) before starting OQ

End D installed climatic chamber

Qualification
3. Phase: OQ-Operational Qualification

Start D installed climatic chamber

• write and approve OQ-Plan

• OQ-tests with empty chamber:
¾ running of the climatic cell: does it work as expected
¾ perform extensive Temperature- and Humidity-Room-Mapping
¾ testing any influence of the climatic conditions (light, open doors)
¾ simulate a power failure and protocol the behavior of the chamber to
make conclusions
• find a representative position for the monitoring sensor
• write and approve OQ-Report (with reported open issues) before starting PQ

End D Climatic chamber ready for operation

Qualification
4. Phase: PQ-Performance Qualification

Start D running / working climatic chamber (without samples)

• write and approve PQ-Plan

• repeat the OQ-tests with filled chamber:
¾ running of the climatic cell: does it work as expected
¾ perform extensive Temperature- and Humidity-Room-Mapping
¾ testing any influence of the climatic conditions (light, open doors)
¾ simulate a power failure and protocol the behavior of the chamber to
make conclusions
• Go live with the on-line monitoring, if available
• Calibrate the sensors
• write + approve PQ-Report (without any open issues)

End D completely qualified climatic chamber

Qualification
4. Phase: PQ-Performance Qualification

perform extensive Temperature- and Humidity-Room-Mapping

Possible data logger

positions to map
temperature and
humidity
Qualification

data logger to collect temperature

and humidity data
Qualification

1. Qualification of stability chambers:

1.1 General aspects
1.2 URS, analysis of local conditions
1.3 Qualification: DQ, IQ, OQ, PQ
1.4 periodic Re-Qualification

2. Calibration of equipment:
3. Maintenance of stability chambers:
Qualification
Periodic Re-Qualification

Start D running climatic chamber

• Strategy:
Review of qualification status after a pre-defined time period

• write and approve Re-Qualification-Plan

• check all relevant parameters (i.e. MSR)
• is the change documentation complete?
• Repeat the Temperatur- and Humidity- Room-Mapping
• write and approve PQ-Report before writing the Final Report

End D re-qualified climatic chamber

Calibration

1. Qualification of stability chambers

2. Calibration of equipment of stability chambers

3. Maintenance of stability chambers

Calibration
concepts

9 Calibration of equipment (e.g. sensors for on-line monitoring) in place

D Calibration including whole measured distance
D one point calibration at set point

9 Calibration of equipment (e.g. data-logger for temperature mapping) with a

certified, adjusted master tool (Certified Institution)
D Calibration without measured distance
D Multi point calibration
D all set points must lie within calibration range
D Data logger must be suitable for intended conditions (e.g. 40°C / 75%r.H.)
Maintenance

3. Maintenance of stability chambers

3.1 periodical maintenance, technical support
3.2 microbiological monitoring, cleaning
3.3 on-line monitoring
3.4 Alarm-System
3.5 Change Control
3.6 Temperature- or Humidity-Deviations
Maintenance
periodical Maintenance, technical support

9 Defined maintenance according service-protocol:

checking pressure, air flow, valves

9 on-going maintenance including auxiliary media (steam, cooling water)

9 support in any case of emergency, 24h a day

Maintenance

service-protocol to document pressure

Maintenance

3. Maintenance of stability chambers:

3.1 periodical maintenance, technical support
3.2 microbiological monitoring, cleaning
3.3 on-line monitoring
3.4 Alarm-System
3.5 Change Control
3.6 Temperature- or Humidity-Deviations
Maintenance
microbiological monitoring and cleaning

9 periodical microbiological monitoring according written procedure

9 periodical cleaning of stability chambers including according written procedure,
e.g. every 6 months
9 define acceptance criteria
Maintenance

3. Maintenance of stability chambers

3.1 periodical maintenance, technical support
3.2 microbiological monitoring, cleaning
3.3 on-line monitoring
3.4 Alarm-System
3.5 Change Control
3.6 Temperature- or Humidity-Deviations
Maintenance
on-line monitoring (Temperature and Humidity)

9 confirm the defined position for any monitoring sensor which is used
9 to visualize the climatic conditions, generating GMP-Data
9 to document any deviations
9 Date could be requested by inspectors
9 monitoring sensors are calibrated annually
Maintenance
on-line monitoring (calibrated sensor)
Maintenance

3. Maintenance of stability chambers

3.1 periodical maintenance, technical support
3.2 microbiological monitoring, cleaning
3.3 on-line monitoring
3.4 Alarm-System
3.5 Change Control
3.6 Temperature- or Humidity-Deviations
Maintenance
Alarm Systems

9 double- control of the climatic limits using another, different,

independent alarm system
Maintenance

3. Maintenance of stability chambers

3.1 periodical maintenance, technical support
3.2 microbiological monitoring, cleaning
3.3 on-line monitoring
3.4 Alarm-System
3.5 Change Control
3.6 Temperature- or Humidity-Deviations
Maintenance
Change Control

Approved changes
9 Planned change has to be assessed
9 Relevant changes have to be approved by Quality Assurance before realization

Emergency changes
9 Approved by Quality Assurance after implementation of the change
Maintenance

3. Maintenance of stability chambers

3.1 periodical maintenance, technical support
3.2 microbiological monitoring, cleaning
3.3 on-line monitoring
3.4 Alarm-System
3.5 Change Control
3.6 Temperature- or Humidity-Deviations
Maintenance
Temperature- or Humidity Deviations

9 Short time deviations are allowed by ICH

(…short term spikes due to opening of doors…are accepted as
unavoidable…)
9 important deviations have to be documented (i.e. in a „Deviation Report”)
according ICH
(…Excursions that exceed the defined tolerances for more than 24 hours
should be describes in the study report…)
Stability Chambers
Overview F. Hoffmann-La Roche (post approval)

Chamber Conditions
T (°C) r. H. (%)
D all ICH conform KTZ 1, 8, 10 5 ---
conditions are available
KTZ 4 15 ---
KTZ 3, 9 25 60
KPS E +I 30 65
KTZ 5 30 75
KTZ 7 40 75
Stability Chambers
Example: 25°C/60% r.H. Chamber
Stability Chambers
Example: 25°C/60% r.H. Chamber

drawer
Stability Chambers
Example: 5°C climatic chamber

Calibrated on-
line monitoring
sensor (Pt100)
Stability Chambers
Example: 25°C/60% r.H. climatic chamber

Flash light
(emergency case)

Calibrated on-line
monitoring sensor
(Temperature and
Humidity)
Stability Chambers
Example: 25°C/60% r.H. climatic chamber

access control-
systems escape route

ramp
 Thanks for your attention!

Dr. Mathias Kramer

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