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: 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 OQ

4.Phase PQ MQR

DQ: Design Qualification MQP: Master-Qualification Plan MQR: Master-Qualification Report IQ: Installation Qualification 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. 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

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 doorsare 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. (%) ----60 65 75 75 5 15 25 30 30 40

all ICH conform conditions are available

KTZ 1, 8, 10 KTZ 4 KTZ 3, 9 KPS E +I KTZ 5 KTZ 7

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

We Innovate Healthcare