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							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
      QA, Engineer, technician, system owner (teamleader)
      the team determines your success

•   approach: planning doing 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    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     Order of the designed chamber
Qualification
2. Phase: IQ-Installaltion Qualification


Start    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     installed climatic chamber
Qualification
3. Phase: OQ-Operational Qualification


Start    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     Climatic chamber ready for operation
Qualification
4. Phase: PQ-Performance Qualification


Start    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     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     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      re-qualified climatic chamber
Calibration



  1. Qualification of stability chambers

  2. Calibration of equipment of stability chambers

  3. Maintenance of stability chambers
Calibration
concepts



  Calibration of equipment (e.g. sensors for on-line monitoring) in place
       Calibration including whole measured distance
       one point calibration at set point


  Calibration of equipment (e.g. data-logger for temperature mapping) with a
    certified, adjusted master tool (Certified Institution)
       Calibration without measured distance
       Multi point calibration
       all set points must lie within calibration range
       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




  Defined maintenance according service-protocol:
   checking pressure, air flow, valves

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

  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




  periodical microbiological monitoring according written procedure
  periodical cleaning of stability chambers including according written procedure,
  e.g. every 6 months
  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)




  confirm the defined position for any monitoring sensor which is used
  to visualize the climatic conditions, generating GMP-Data
  to document any deviations
  Date could be requested by inspectors
  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




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


Emergency changes
  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



   Short time deviations are allowed by ICH
(…short term spikes due to opening of doors…are accepted as
unavoidable…)
   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. (%)
        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
We Innovate Healthcare