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: 40C 2C / 75 % r.H. 5 % r.H.)
- limits, according ICH Q1A,
- additional conditions
(e.g. Humidity in 5C-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
MQP

DQ

2.Phase
IQ

3.Phase

4.Phase

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:
running of the climatic cell: does it work as expected
perform extensive Temperature- and Humidity-Room-Mapping
testing any influence of the climatic conditions (light, open doors)
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:
running of the climatic cell: does it work as expected
perform extensive Temperature- and Humidity-Room-Mapping
testing any influence of the climatic conditions (light, open doors)
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. 40C / 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 doorsare 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

D all ICH conform

conditions are available

Conditions
T (C)

r. H. (%)

KTZ 1, 8, 10

---

KTZ 4

15

---

KTZ 3, 9

25

60

KPS E +I

30

65

KTZ 5

30

75

KTZ 7

40

75

Stability Chambers
Example: 25C/60% r.H. Chamber

Stability Chambers
Example: 25C/60% r.H. Chamber

drawer

Stability Chambers
Example: 5C climatic chamber

Calibrated online monitoring

sensor (Pt100)

Stability Chambers
Example: 25C/60% r.H. climatic chamber

Flash light
(emergency case)

Calibrated on-line
monitoring sensor
(Temperature and
Humidity)

Stability Chambers
Example: 25C/60% r.H. climatic chamber

access controlsystems

escape route

ramp

Thanks for your attention!

Dr. Mathias Kramer

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