Validation may be defined as “ Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes.” Dry Heat Moist Heat Gas (Ethylene oxide) Radiation (Gamma or Electron) Filtration Others - UV, Steam and formaldehyde, hydrogen peroxide

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Validation of sterilization methods
Presented by
Rajesh Sanyasi
M.Pharm 1st yr .
Department of PA & QA

2. Validation of sterilization methods
 Validation may be defined as
“ Establishing documented evidence which provides a
high degree of assurance that a specific process will
consistently produce a product meeting its pre-determined
specifications and quality attributes.”
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3. Sterile Products
What is the definition of “sterile”?
 Free from microorganisms
In practice no such absolute statement regarding absence of
microorganisms can be proven.
 This referred to as the Sterility Assurance Level (SAL)
 Organisms are killed in an exponential fashion.
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4. Commonly used methods of sterilization
 Dry Heat
 Moist Heat
 Gas (Ethylene oxide)
 Radiation (Gamma or Electron)
 Filtration
 Others - UV, Steam and formaldehyde, hydrogen peroxide
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5. Dry Heat sterilization
 Dry heat is one of the most commonly used methods to
sterilize and depyrogenate pharmaceutical components
and products.
 Higher temperatures and longer exposure times required.
 Dry heat sterilization is often used for heat-stable oils,
ointments and powders.
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6. Typical cycles:
 160 C for 120 minutes
 170 C for 60 minutes
 180 C for 30 minutes
 Tunnels used for the sterilisation of glass vials may use much
higher temperatures (300 ) for a much shorter period
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7.  Used for:
 Glassware and product containers used in aseptic manufacture,
non aqueous thermostable powders and liquids (oils)
 Also used for depyrogenation of glassware
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8. Validation studies of Dry-heat sterilizers
 Validation studies conducted on dry-heat sterilizers can be
divided into two basic components.
 One component envelops all the physical processes, which must
be validated, such as temperature control, air particulate levels,
and belt speeds.
 Second component involve the process destroys both microbial
and pyrogenic contaminants.
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9. MOIST HEAT STERILIZATION
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 Heating an article is one of the earliest forms of
sterilization practiced.
 Moist heat, as the name indicates, utilizes hot air that is
heavily laden with water vapour and where this moisture
plays the most important role in the process of
sterilization.
 Example: Autoclave

10. VALIDATION OF AUTOCLAVE
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 This procedure is used to assess the efficiency and
performance of autoclaves.
 A quality assurance procedure used to ensure that the
autoclave reaches adequate temperature for an adequate
amount of holding time to sterilize biological agents and
wastes.

11. Performance Qualification
 Heat-distribution studies include two phases:
1) Heat distribution in an empty autoclave chamber,
2) Heat distribution in a loaded autoclave chamber.
“The trips where the wires are soldered should not make contact
with the autoclave interior walls or any metal surface.”
Biological Indicators:
The most commonly used biological indicator is Bacillus
stearothermophius, being the most resistant to steam autoclaving.
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12. Heat-Penetration Studies:
 This is the most critical component of the entire validation
process. The main purpose is to determine the cold spot inside
the commodity.
 The difference in temperature will be calculated based on the
temperature recorded by the thermocouple inside the container
at the coolest area of the load.
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13. Validation of Membrane Filteration
 Introduction
Unit operation of filtration is the separation of solids from a liquid by
passage through a filter medium. Membrane filtration is used for
sterilization of drug product and used in sterilization process.
There are two types of filter used in filtration process:
Depth filters: Consist of fibrous or granular materials so packed as to
form twisted channels of minute dimensions.
Membrane filters: These are porous membrane about 0.1 mm thick,
made of cellulose acetate, cellulose nitrate, polycarbonate, and
polyvinylidene fluoride, or some other synthetic material.
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14. Validation studies
 Operating condition Time :
Long processing time could allow bacteria filtered which have
been trapped by the filter. Filter manufacturer can provide the
data on the retention tests that have been conducted for specific
membrane and generally suggest that filter should retain bacteria
excess of 48hr.
 Temperature :
Manufacture of filter recommended the limit of 20-25ºC.
Pressure : Inlet pressure to the filter must be monitored to ensure
that there is no potential for structure damage. The differential
pressure across the membrane must comply with the filter
manufactures recommended limits.
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15. References
 Nash, R.A. and Watcher, A. H. “Pharmaceutical process
validation ”; Third edition Agalloco James.
 Carleton J. Fredric “Validation of Pharmaceutical Processes” ;
Third edition Pharmaguideline.
 Berry I.R., and Nash R.A., ”Pharmaceutical Process validation”
second edition, revised and expanded; Marcel Dekker series; 83-
110
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