Validation is the process of checking of the process, equipment and method whereas qualification is solely done for equipment and qualification of instrument helps in quality of pharmaceutical product.

1. Qualification of Dry
Heat Sterilization.
DEEPAK V. SHANBHAG
M.PHARM FIRST YEAR
DEPARTMENT OF PHARMACEUTICAL QUALITY ASSURANCE
BHARATI VIDYAPEETH COLLEGE OF PHARMACY, KOLHAPUR.
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2. Contents
 Introduction to dry heat sterilization.
 Types of Dry heat Sterilization.
 Validation of dry heat sterilization.
 Batch Oven Validation.
 Tunnel system Validation.
 Validation of dry heat sterilization process.
 Biological process validation in sterilization cycles.
 Empty Tunnel heat distribution.
Operational Qualification of dry heat sterilization.
 Conclusion.
References.
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3. Introduction to Dry Heat Sterilization.
 Dry heat is the most commonly used methods to sterilize and/or depyrogenate pharmaceutical
components (glasswares) and products. Most often, it is used for depyrogenation of parenteral
containers is performed utilizing a dry heat oven.
 The process of sterilization within a chamber or hot air tunnel is a critical process and there is
regulatory requirement for validation of the process in most countries.
 While, validation is defined as the documented procedure of obtaining, recording and
interpreting results to ensure that the dry heat sterilization process has been and will be
consistently efficient.
 Dry heat sterilization validation consists of accurately measuring the temperature at critical
points within the sterilization chamber throughout the process and also enough to achieve the
sterility.
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4. Types of dry heat sterilizers.
Commonly employed dry heat sterilizers in pharmaceutical industry are-
 Forced Convention batch sterilizers.
 Infrared Tunnel sterilizers.
 Forced convention tunnel sterilizers.
 Continuous flame sterilizers microwave
 Laser/Plasma sterilizers.
 But commonly utilized dry heat sterilizers in pharmaceutical industry are-
 Conventional hot air oven.
 The tunnel system dry heat sterilizers.
 (Major difference between the hot air oven and tunnel system, as far as validation is concerned,
is the belt or line of speed variable with the tunnel system.)
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5. Types of Dry heat sterilizers
Conventional hot air oven. The tunnel system.
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6. Validation of Dry heat sterilization-
Batch oven validation.
1. Air balance determination: Air should be balanced so that positive pressure is exerted to the non sterile side when
the door is opened.
2. Heat distribution of an empty chamber: Thermocouples should be situated according to a specific predetermined
pattern. Repeatability of temperature attainment and identification of the cold spot can be achieved if the
temperature range is ±15°C at all monitored locations. Heat-distribution studies can also be conducted as a function
of variable airflow rates.
3. Heat-penetration studies: These studies should be designed to determine the location of the slowest heating point
within a commodity at various locations of a test load in the sterilizer. Thermocouples are placed in the commodities
located in the areas likely to present the greatest resistance to reaching the desired temperature. Normally, three
replicate cycles are run at Minimum and maximum temperatures. The cold spot must not move during the replicate
studies. Other variations in the cycle affecting heat penetration at the cold spot can be studied, and these might
include
(a) test load variations,
(b) temperature set point variations, and
(c) variations in the time of exposure.
4. Mechanical repeatability: During all these studies, mechanical repeatability in terms of air velocity, temperature
consistency, and reliability and sensitivity of all the oven and instrumental controls must be verified.
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7. Validation of Dry heat sterilization-
Tunnel system sterilizers.
 Principles as described above for the physical process validation of batch ovens apply also in the
validation of tunnel sterilizers; however, in addition to the variables affecting batch oven
validation, tunnel sterilizers have an extra variable-belt speed. This variable can be held
constant by maintaining the same belt speed throughout the validation process and not
changing it after validation has been completed.
 Other than above, Air balance determination, Heat distribution of an empty chamber, heat
penetration studies, mechanical repeatability are done for tunnel systems too.
 This becomes a part of installation qualification (IQ) and performance Qualification (PQ).
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8. Validation of Dry heat sterilization
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9. Validation of Dry Heat Sterilization Process
Installation Qualification (IQ)- Validation of a dry heat sterilization cycle begins with the execution of the Installation
Qualification (IQ) protocol on the equipment (oven, tunnel, or cabinet) which will be used to perform the dry heat
sterilization. The IQ protocol verifies and documents that the equipment is installed correctly and meets all of the
manufacturer and user requirements. During the execution of the IQ protocol, the equipment drawings, calibration status of
critical instruments, instrument and valve information, utility information, and standard operating procedures for the
equipment are all confirmed.
Operational Qualification (OQ) - The next step in the validation of a dry heat sterilization cycle is the execution of the
Operational Qualification (OQ) protocol of the equipment. The OQ protocol verifies and documents that the equipment is
programmed and operating correctly, and is able to meet all of the manufacturer and user requirements. Execution of the
OQ protocol involves verifying the parameters/settings (e.g. general system options, cycle length, airflow, sterilization
temperature) of the dry heat sterilization cycle(s). It also ensures that the system alarms are operating correctly, that the
equipment is functioning properly (e.g. verification that the control system functions as specified by the equipment
manufacturer or system interlocks), and that the equipment is able to achieve and maintain the required sterilization
conditions during the dry heat sterilization cycle(s).
Performance Qualification (PQ) - The execution of the IQ and OQ protocols covers the validation of the equipment. In order
to validate a dry heat sterilization cycle, a Performance Qualification (PQ) protocol must be executed. The PQ demonstrates
that the dry heat sterilization cycle(s) can repeatedly achieve the required Sterility Assurance Level (SAL) 1. In order to
confirm that the necessary SAL can be reached, the dry heat sterilization cycle must be temperature mapped. During the
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10. Validation of Dry Heat Sterilization Process
PQ, biological indicators should be placed throughout the chamber. Typically Bacillus atrophaeusbiological indicators are
used to demonstrate that the dry heat sterilization process can consistently deliver the required microbial inactivation.
The biological indicators used must have a population of ≥ 1 x 106 organisms, and a D-value of ≥ 2.5. Incubation and
enumeration of the biological indicators demonstrates whether or not the required SAL was reached. If the biological
indicator population has been completely reduced (no growth of the biological indicators is observed after incubation),
this indicates that the necessary SAL has been reached during the sterilization cycle. For depyrogenation cycles,
endotoxin vials containing a known amount of E. coli endotoxin should be used to demonstrate the required pyrogen
removal. A 3 log reduction of the endotoxin level must be achieved in order for a depyrogenation cycle to be considered
successfully validated.
 Temperature Mapping
To perform a temperature mapping, data loggersare placed throughout the equipment chamber (distribution data
loggers) and the load being sterilized (penetration data loggers). In order to temperature map a depyrogenation cycle it
is sometimes necessary to use thermal barriers to protect the data loggers from the extreme heat. All of the data
loggers used should have at least a 3 point NIST-traceable calibration performed prior to use.
For lower temperature (≥160°C) dry heat sterilization, confirmation that the minimum SAL is attained is required. To do
this, the temperature data recorded by the penetration data loggers during the cycle is evaluated to determine the
lethality value (FH). Typically, the required FH is determined by the multiplying the D-value of the biological indicator used
by 12.
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11. Validation of Dry heat sterilization Process-
Biological process validation in sterilization cycles.
If a dry-heat process is claimed to produce sterile commodities, micro-organisms known to be
most resistant to dry heat must be used to prove the ability of the dry-heat cycle to destroy
them at the coolest location in the load. If the dry-heat process is claimed to produce both
sterile and pyrogen-free commodities, validation studies must be done using both micro-
organisms and microbial endotoxins. The most widely used biological indicators for dry heat
have been spores of B. subtilis; however, spores of other bacterial species may be used if they
are shown to have greater resistance to dry heat. At 170°C, even the most resistant microbial
spore form will have a D value of 6 to 10 min. At temperatures required to depyrogenate,
microbial spores will have D values of only a few seconds. The acceptable Z value for microbial
dry-heat resistance is 20°C.
The step by step process for microbial validation is explained further-
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12. Validation of Dry heat sterilization Process-
Biological process validation in sterilization cycles.
Select the type of
biological indicator and
calibrate it.
Place spore carrier in 12
different bottles on
coolest area of the
oven.
Run a complete cycle
using the desired
loading pattern.
aseptically transfer the
spore strip to vessels of
culture media.
Determine the number
of survivors by plate-
counting and calculate
spore log reduction
(SLRs) using formula.
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13. Validation of Dry heat sterilization-
Empty tunnel heat distribution
 Objectives of this test-
 Ability of the sterilizer to hold the required sterilization parameters.
 Ability of the sterilization cycle control mechanisms to operate as intended.
 Test procedure-
 A review of all sterilization specifications assigned to the sterilizer under consideration shall be made, with the
specifications cycle requiring the maximum peak dwell temperature and heating rate to be selected for the empty
sterilizer heat distribution runs. During the empty sterilizer heat distribution runs, sterilizer parameters and
equipment component status shall be visually monitored to confirm applicable control operations.
Acceptance Criteria-
 The distribution runs must meet the time and temperature requirements of the corresponding specifications or
operating procedures.
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14. Operational Qualification of dry heat
sterilization
The intent of sterilizer OQ studies will be to:
 Confirm that sterilizers are capable of processing at established time and temperature ranges that assure conformance with respec-
tive specification requirements
 Confirm that established sterilization cycles deliver a uniform and reproducible heat input to products assigned to each cycle
 The sterilization test functions required to qualify or validate the sterilizer will include process heat distribution, process heat
penetration, and process microbial and depyrogenation validation, as applicable.
 The OQ phase of sterilizer validation shall consist of the development of an information
package fulfilling the documentation requirements of the generic equipment operational
qualification.
The tests conducted for the operational qualification(OQ) of dry heat sterilization are-
 Heat distribution.
 Heat Penetration.
 Componentry Microbial and pyrogen challenges.
Everything the process carried out for operational qualification should be documented as
format given previously.
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15. Conclusion
 Dry heat sterilization is the process for the removal of microbial and pyrogen contamination of
any glassware or any sterile product.
 For this dry heat sterilizers equipments are used and for which it needs to be validated.
 The equipments includes hot air oven and dry heat tunnel systems and for which validation
tests includes validation of dry heat sterilization process and equipment wholely.
 The tests include the usage of biological indicators while validating dry heat sterilization
process.
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16. References
 https://biologicalindicators.mesalabs.com/2015/12/14/validation-of-dry-heat-sterilization-
processes/
 https://www.pharmatutor.org/articles/validation-dry-heat-sterilization-methods
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17. THANK YOU
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