Qualification of Autoclave &

Hot Air Oven

Compiled by: Kshama Shah QA-14

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Autoclave Qualification

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Types of autoclave:

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Project Implementation Process

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 Design Qualification (DQ) -
u DQ is performed by documented comparison of URS and FDS, focussed on GMP-relevant
topics
u all requirements set up be the URS (resulting from the risk analysis) should be met,
traceability to risk analysis and URS should be given
u deviations from the requirements of the URS must be evaluated whether acceptable or not
(→GMP-requirements)
u Supplier Audits (quality system, software development) should be implemented in this
phase
Approval of DQ protocol and report respective approval of
URS/FDS comparison by defined persons (VMP) → →→
→Start of project change control
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Factory Acceptance Test (FAT) / Site Acceptance Test (SAT)-
u FAT
•Qualification staff should join FAT
•Preliminary documentation should be available and should be checked during FAT
(incl. IQ and OQ -protocols)
•First formal check of P&I-Diagram by qualification staff
•Definition of test program on basis of suppliers possibilities
•Structured FAT can substitute some IQ(OQ)-testing
u SAT
•Basis for SAT should be mechanical completion of autoclave
•SAT should be performed as Pre-IQ / Pre-OQ / can substitute some IQ / OQ
testing.

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Installation Qualification (IQ) -
u points to be checked
1. Calibration of the different sensors
2. Three points for temperature/pressure
3. One point for timer or paper speed of the recorder
4. Availability of relevant SOPs (operation, maintenance), at least as draft version
5. Check of the supplier documentation
6. Completeness
7. Formal correctness
8. Correctness of content

u Finalisation of IQ
1. Deviations must be evaluated
2. In case of GMP-critical deviations (e.g. wrong type of sensors), IQ not successful →remedy of deviation
and repetition of IQ (Change Control)
3. In case of non GMP-critical deviations, a pre-approval of the IQ is possible in order to start next
qualification step

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Operational Qualification (OQ)
u Pre-requisites
1. (Pre-)Approval of IQ
2. Used measuring devices (e.g. Kaye system, data loggers) should be calibrated before performing
measurement (and afterwards)

u Function testing of all procedures & sequences

1. Tightness and stability of piping after performing a sterilisation cycle (Visual checks!)
2. Loading and unloading tests
3. Interlocks of doors
4. Check of programs
5. Fractionated pre-vacuum
6. Heating phase
7. Equilibration time
8. Sterilisation time
9. Drying and Cooling
10. Correct re-start after power failure

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…Points
Points to be checked
u Check of alarms
1. Temperature too high or too low
2. Pressure too high or too low (pressure variations)
3. Time limits of process steps
4. Utility supply
5. Cable break of sensors
6. ...
u Computer Validation related points
o User access and audit trail
o Data storage / Print Out
o Electromagnetic failure, radio frequency test

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 …Points
Points to be checked
u Check of steam quality (should be covered by qualification of clean steam
system)
u Check of chamber tightness
o Possible acceptance criteria: pressure drop ≤1,3 mbar / min
o Procedure: Evacuation of the chamber on a predefined pressure and closing of all
valves. Measurement for 10 min
u Bowie-Dick-Test for sterilisation cycles with saturated steam
o Use of test kids
o Colour change of indicator complete
u Integrity of aeration filter
o Water Intrusion Test for hydrophobic filters

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…Points
Points to be checked
Heat distribution check of the empty chamber (Identification of cold spots)
Acceptance Criteria
u Correct process incl. recording without alarms
u Pre-defined maximum standard deviation not exceeded for validation sensors
u Pre-defined maximum allowed deviation from the mean value for single
validation sensors not exceeded for validation sensors
u Pre-defined maximum allowed deviation from the mean value of the validation
sensors for control and documentation sensors not exceeded

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…Points
Points to be checked
u Heat distribution check of the empty chamber (Identification of cold spots)
u Method
1. Repeated measurement of the empty chamber (e.g. 3 times)
2. Use of in minimum 10 to 12 sensors / m3 of chamber volume
3. One sensor should be near to the control sensor respect. near to the condensate
drain
4. Documentation of the exact localisation of the used sensors

u Finalisation of OQ
 Deviations must be evaluated
 In case of GMP-critical deviations (e.g. bugs in sterilisation cycles), OQ not
successful →remedy of deviation and repetition of IQ (Change Control)
 In case of non GMP-critical deviations, a pre-approval of the OQ is possible in order
to start next qualification step
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Performance Qualification (PQ)- Process Validation (PV)

u Definition as Performance Qualification or as Process Validation possible (in

reality combination of both aspects)
u Focus of PQ on autoclave & Focus of PV on product quality
u Test with product / material to be sterilised or with adequate placebo
u Combination of heat penetration test controlled by external temperature
sensors and bio-indicators
u Detailed test plan including a risk based approach for planned procedure to be
defined

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Hot Air Oven

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Introduction

• A validation programme involves various components in

pharmaceutical organisation related to process, equipment and
product.
• Equipment Validation ensures that an instrument is appropriate for
its intended use.
• Dry heat is one of the most commonly used method to sterilize and
depyrogenate pharmaceutical components and product.

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Types of Dry Heat Sterilizers

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 Equipment used for validation testing of oven are listed below:

u Resistance temperature detectors

u Thermocouples
u Data logger
u Constant temperature bath
u Stopwatch
u Voltmeter
u Optical tachometer

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Design qualification:
• The DQ outline the key features of the system designed to address
the user requirement, regulatory compliance and selection rationale
of a particular supplier.

The following are the key considerations for DQ:

u Physical dimensions of the equipment and accessories
u Suitable operating environment of the instrument
u Health and safety requirement

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Installation Qualification

It is carried out after or concurrently with the installation of the equipment at

the user’s premises.
• The purpose is to provide documentary evidence that the correct equipment
has been received and installed as per plan and protocol.
• IQ documents should be reviewed and approved by designated responsible
individuals.
• It includes details of-
Structural- Check dimensions, presence of seal
Filters- Proper identification,type,size,air capacity, flow rate

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u Electricals- Proper identification, safety cutoff
u HVAC- System provides the temperature and pressure differential required.
u Air supply- Identify source, duct size.
u Air or natural gas- Check that the source and type of supply are consistent
with the manufacturer’s recommendations.
u Heaters- Record the manufacturer's model no., the no. of heating elements.
u Blowers- Check for use of correct fan belt & that is in good condition.

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Operational Qualification

It is documented verification that the system or subsystem performs as

intended throughout all specified operating range.

• The OQ document should be reviewed and signed by the required

department representatives.
• The components of system must satisfy the operating ranges as determined
by the purchase order specifications.
• Each of the following process components must be identified & the
operating performance & range determined.

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Continue…
u Temperature monitors
u Cycle timer-
The accuracy of timer must be determined, so that assurance is
provided for cycle time.
u Door interlocks-
If a unit is equipped with double doors, the interlocks must operate
such that the door leading to the aseptic area cannot be opened if the
door to the non-aseptic area is opened.
u Heaters-
All of the heating elements must be functional.
u Blowers-
The air velocity consistent and motor speed of blowers should be
noted in the OQ records.

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 Continue…

u Cooling Coils-
If coils are present, the type and size of the coils and temperature of the cooling
medium at the inlet and outlet of the coils should be recorded.
u Chamber leaks-
The perimeter of the doors for batch sterilizers should be checked for air leakage
while operating.
u Particulates counts-
Particulate count should be checked within the containers before and after
sterilization to quantitate the particle load contributed to the product by
sterilization process

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Performance Qualification
u Verifies that the equipment performs according to design specifications and
user defined requirements in a reliable & reproducible manner under normal
production conditions
• Physical -
Heat penetration studies on empty chamber
Heat distribution study on loaded chamber
Heat penetration study on loaded chamber

• Microbiological-
Bio-challenge/ Pyro-challenge studies

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Thank You……

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