EQUIPMENT VALIDATION :
HOT AIR OVEN
Mr. Sagar Kishor Savale
[Department of Pharmaceutics]
Department of Pharmacy (Pharmaceutics) | Sagar savale
• Definition of Equipment validation
• Types of Dry Heat Sterilizers
• Principles of Heat Transfer And Circulation
• Validation Test Equipment
• Basic Validation Approach
• Process Qualification Cycle Development
• Routine Monitor After Validation
• A validation programme involves various components in
pharmaceutical organisation related to process, equipment and
• 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.
Types of Dry Heat Sterilizers 1
Conventional Hot Air Oven
HOT AIR OVEN 2,3,I
• Higher temperatures and longer exposure times required
• Typical cycles:
160°C for 120 minutes
170°C for 60 minutes
180°C for 30 minutes
• Used for:
glassware and product containers used in aseptic manufacture, non
aqueous thermostable powders and liquids (oils)
also used for depyrogenation of glassware.
The hot air oven is the equipment which is utilized to provide the dry heat
medium and it must be validated to ensure that the system is able to provides
sterile and depyrogenated components, on a reproducible basis
Principles of Heat Transfer and Circulation 1,2,II
Heat flows from one body to another due to the temperature difference
Photon propagation will transfer thermal energy to the object and increase
the surface temperature
Booster fan or blowers are used in the oven to increase the circulation of
the heat throughout the load.
Validation Test Equipment 1,IV
Equipment used for validation testing of oven are listed below:
Resistance temperature detectors
Constant temperature bath
Basic Validation Approach 3,4, V
• 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:
Physical dimensions of the equipment and accessories
Suitable operating environment of the instrument
Health and safety requirement 95/29/2016
• 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
• It includes details of-
Structural- Check dimensions, presence of seal
Filters- Proper identification,type,size,air capacity, flow rate
Electricals- Proper identification, safety cutoff
HVAC- System provides the temperature and pressure differential required.
Air supply- Identify source, duct size.
Air or natural gas- Check that the source and type of supply are consistent
with the manufacturer’s recommendations.
Heaters- Record the manufacturer's model no., the no. of heating elements.
Blowers- Check for use of correct fan belt & that is in good condition.
• 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
• 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.
The accuracy of timer must be determined, so that assurance is
provided for cycle time.
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.
All of the heating elements must be functional.
The air velocity consistent and motor speed of blowers should be
noted in the OQ records.
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
The perimeter of the doors for batch sterilizers should be checked for
air leakage while operating.
Particulate count should be checked within the containers before and
after sterilization to quantitate the particle load contributed to the
product by sterilization process
Performance Qualification 5
• 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
Bio-challenge/ Pyro-challenge studies
Heat Penetration Studies On Empty Chamber 1,2,IV
• To identify heat distribution patterns including slowest heating points
• Multiple temperature sensing devices should be used(Thermocouples)
• Temperature profile locate hot/cold areas in the sterilizer by mapping
temperature at various locations
• A detailed diagram of the location of the thermocouples should be included
in the empty chamber data file
Heat Distribution Study on Loaded Chamber1,2
• Multiple thermocouples throughout chamber (not inside product
containers) to determine effect of load configuration on temperature
• Temperature distribution for all loads using all container sizes used in
production should be tested.
• Repeat runs should be performed to check variability.
• Temperature profile for each chamber load configuration should be
Heat Penetration Study on Loaded Chamber 1,2
• Designed to determine the location of the slowest heating point within a
oven at various locations.
• Each size & type of material should be tested by penetration studies.
• Hot areas in the load are more important for heat labile items.
• Data obtained by placing thermocouples inside the container in such a way
as to ensure contact with the surface.
Bio-Challenge/ Pyro-Challenge Studies 1,2
• The challenge should demonstrate the lethality delivered by the cycle with
either microorganisms or endotoxin
• Resistant bacterial spores are available as BIs primarily in the form of:
• Spore strips:
• Spore suspension:
Process Qualification Cycle Development 1,2,II
• The sterilization cycle is designed to inactivate the heat resistant spores as
well as any vegetative cells which could potentially be present during
It is used to express the rate of killing of microorganisms during
The time required at a certain temperature to kill 90% of the organism
Dry heat sterilization:Therotical requirment-170°C,32 min.
The relationship of lethality to temperature is expressed the in Z-
The Z value will define the number of degrees that are required for a
change in the D-value by a factor of 10
Dry heat sterilization Z =20°C
It is a unit of lethality used as a measurement of sterilization
It indicates the equivalent amount of time delivered by a heat process at
a particular temperature.
Routine Monitor After Validation 1,5
• The unit must be monitored so that it remains in a state of control
• This is achieved by the use of various programs including-
It should detailed the cleaning methods used for the equipment, the
SOPs covering each method, and the cleaning materials utilized.
Cleaning materials should be nontoxic and leave no residues.
• Preventive maintenance-
It provides a schedule by which the equipment is maintained.
A proper PM program will help to prevent breakdown during
• Change control-
Changes to the equipment that might compromise the validation
must be brought to the attention of the group or individuals in
charge of the change control program.
It may be required after changes or repairs are made on the unit or
an a predetermined periodic interval.
• All validation information should be easily identified and kept in a
permanent central file, where it can be readily retrieved.
• The validation file should include the following information:
This includes all steps performed in the certification of the equipment .
All original data, results and conclusion must be contained in this file.
All reports should be dated,signed,and approved by the responsible
• Process Qualification Protocol:
The protocol is located in this file.
• Raw Data:
All original data, results, calculation and conclusions must be retained for
empty- and loaded chamber and biochallenge studies
• Process Qualification Report:
It is the formal document available for regulatory review
• Routine Monitoring:
All change-control information and postvalidation mechanical changes are
recorded along with any revalidation work
• Equipment is one of the basic component of pharma processing and
therefore equipment validation is an important aspect.
• Validation of Hot Air Oven is the part of comprehensive validation
program within a company.
• The validation of Hot Air Oven prove its repeatability.
• Equipment validation give the surety that equipment having good
qualification like design, operation, installation and performance
qualification which have predetermined.
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5. Syed Imtiaz Haider. Pharmaceutical Master Validation Plan. The Ultimate
Guide to FDA,GMP and GLP Compliance. informa healthcare;2010. P.