hitesh chaudhari

Validation Of Autoclave:

V alidation Of Autoclave Presented by Hitesh Chaudhari SIPS Guided by: Mrs. Manisha Patel Department of pharmaceutics

Steam under Pressure :

3/19/2011 2 Steam under Pressure The principal advantages of steam sterilization are its simplicity, relatively short processing times, and lack of toxic residues; Parametric release, that is, the release of product for sale without conducting microbiological sterility testing, generally is easily validated; Its main disadvantage is the relatively high temperature (generally lower than dry heat, however) making it unsuitable for many plastic devices and lack of utility for products that are moisture sensitive or moisture impermeable.

Cont..:

3/19/2011 3 Cont.. Products typically sterilized by steam under pressure include small and large volume parenterals (SVPs, LVPs), surgical dressings, water for injection, contact lenses, and so on. To be compatible with steam sterilization, a product must be stable with respect to temperature and moisture, and the product/package must be readily penetrated by steam . Without adequate steam penetration, sterilization can be impeded or defeated entirely.

Steam Sterilization: Autoclaving :

3/19/2011 4 Steam Sterilization: Autoclaving An autoclave is a self locking machine that sterilizes with steam under pressure. Sterilization is achieved by the high temperature that steam under pressure can reach. The high pressure also ensures saturation of wrapped surgical packs. Ideal for metal instruments.

Steam sterilizer (autoclaves):

S team sterilizer (autoclaves) 1. Design Qualification 2. Installation Qualification 3. Operational Qualification 4. Performance Qualification 4.1. Thermodynamical aspects of Sterilization 3.2. Temperature Distribution and Heat Penetration studies

Sterilization only::

S terilization only: The cycle is designed to assure that the probability of survival of the native microflora is no greater than one cell in one million units of the commodity. (10 - 6 probability of nonsterility ) Steam Sterilization Theoretical requirement: 121 o C , 15 min.

Sterilization- Overkill:

S terilization- Overkill The overkill approach provides assurance of sterilization well in excess of the 10-6 probability of non- sterility. For example an F H provided by an overkill cycle may produce a 12- log reduction of a biological indicator that exhibits a high resistance to dry heat.

Sterilization & Depyrogenation::

S terilization & Depyrogenation: Applies to the cycles where the purpose is both sterilization and depyrogenation . Whenever depyrogenation is a desired end point, relatively high temperatures and/or extended heating times are necessary. Thus, microbial lethality delivered by these cycles provides a margin of safety far in excess of a 10- 6 probability of nonsterility .

Slide 9:

D - Value : Time required for one log (or 90%) reduction of microorganism population at base temperature. Determination of Z - Value: Determine the D - value of an organism at min. three different temperatures. Construct a Thermal Death Curve by plotting the logarithm of the D- Value versus temperature.

D-value:

10 10 D-value A measure of the sensitivity of an organism to a sterilization method Decimal reduction time - time at a given temperature required to reduce a population by 1 log

Z value:

Z value In general, for Dry Heat sterilization, Z- Value may be assumed as 20 0C. And for Steam Sterilization as 10 0C. However, it will be appropriate to verify for the biological indicators when they are used to measure the integrated lethality of a dry heat or steam sterilization cycle.

Z-value:

12 12 Z-value A measure of sensitivity of organism to different temperatures Number of degrees needed to alter the D-value by one log Allows for integration of the lethal effect of heat as the temperature changes . Depends on sterilization method Steam: Z = 10º C Dry heat: Z = 21º C

Z-value:

13 13 Z-value Spores, Z = 8 - 12ºC 10º C usually assumed

Lethality Rate::

L ethality Rate: Also defined as : Fo For Steam Sterilization The equivalent sterilization time spent at the base temperature. Tb : 121 o C (For Steam Sterilization)

Various type of steam sterilzers commercially availabe::

V arious type of steam sterilzers commercially availabe: • Saturated Steam • Water Immersion • Water Cascade System • Air-Steam Mixtures • Gravity Air Displacement (unpacked materials sterilization) • Vacuum air Displacement (Packed materials)

Slide 16:

Decimal Reduction Value (D-Value) The exposure to sterilant required to reduce the population of test organism by 90% (one logarithm) under stated conditions. Sterility Assurance Level ( SAL) Probability of a non-sterile unit. As a minimum sterilization cycles are designed to provide a 1 in a million chance of a non-sterile unit. SAL = 10 -6 SAL Sterilization F undamentals

Steam Sterilization Validation Design Qualification ::

Steam Sterilization Validation Design Qualification : Facility layout. Utility requirements and specifications. Required capacity of the sterilizer. Type of materials to be sterilized (Liquids, wrapped ,hollow or porous materials) Requirement for Gravity and/or Prevacuum cycles.

Installation Qualification- CALIBRATIONS::

Installation Qualification- CALIBRATIONS: The following pieces of equipment should be calibrated by removing or in situ: Pressure Gauges Timing Devices Temperature Recording Devices Verification of safety Systems and Devices

Operational qualification::

O perational qualification: The actual operational performance of the electro/mechanical components and utilities should be verified and documented. Clean Steam Generator Air Filtration Systems and compressed air Power Source Heat Exchanger, Cooling Water

Performance qualification:

P erformance qualification External monitoring and recording instruments shall be calibrated before and after the OQ/PQ studies (3 point calibration, ± 0.5 o C tolerance). Uniformity of the temperature distribution in case of Min & Max. loading should be verified by using Thermocouples with 3 replicates. T/C placement shall be documented on a diagram.

Temperature distribution studies::

T emperature distribution studies: At least one T/C shall be placed located in the steam exhaust line or adjacent to the equipment temperature controller. T/C should be secured inside the chamber according to a definite arrangement. Teflon tape can be used to secure T/Cs. The trips where the wires are soldered should not make contact with the autoclave interior walls. Min. 10-12 T/C ‘s shall be used and they should not be inserted in the load. Data should be recorded during the whole cycle at 1 min. intervals. Why? To identify the location of the cool spot and the effect of the load size and/or configuration on the cool spot location.

Calibration of Thermocouples::

C alibration of Thermocouples: Accuracy of thermocouples should be + 0.5 o C. Temp accuracy is especially important in steam sterilization validation because an error of just 0.1 o C in temp measured by a faulty thermocouple will produce a 2.3 % error in the calculated F o value. Thermocouple accuracy is measured by National Bureau of Standards. Thermocouples should be calibrated before and after a validation experiments at two temperature: 0 o C and 125 o C. Any T/C that senses a temp of more than 0.5 o C away from the calibration temp bath should be discarded. Temp recorders should be capable of printing tempo data in 0.1 o C increments.

Heat penetration- Accepatance criteria::

H eat penetration- Accepatance criteria: Thermocouples should be inserted into the load. At least three biological indicators and T/C’s shall be placed around the cold spot. External T/C readings should comply with manufacturer’s specifications (with Max ± 1 O C difference) Biological indicator (bacillus stearothermophilus ) results should ensure the 6-log reduction and Lethality calculation should verify the Equivalent F o (15 min. at 121 o C ) value for defined cycle.

Air Removal Test::

A ir Removal Test: The ability of the pre-vacuum autoclaves to effectively remove the air and noncondensable gases should be tested. If the air is not effectively removed, air pockets will occur in the chamber and sterilization conditions will not be attained. Bowie-Dick or DART Test pack, the uniformity of the colour change on the indicator sheet should be checked. (3.5 min. at 134 o C )

Leak rate Test::

L eak rate Test: The presence of air prevents proper penetration of the load by steam and thus inhibits sterilization. Air leaking from outside into the chamber at the end of sterilization cycle will contaminate the load. A leak rate equivalent to a rate of change in pressure of 1 mm Hg/min. over a period of 10 min. after stabilization is the maximum permitted rate.

STERILIZATION VALIDATION-GENERAL CHANGE CONTROL AND REVALIDATION:

STERILIZATION VALIDATION-GENERAL CHANGE CONTROL AND REVALIDATION Any changes to the sterilization equipment and/or related utilities should be evaluated by a Change Control Procedure. Typical Changes Requiring Revalidation Any changes in operating cycle ( i.e:temperature , time, belt speed, chamber pressure) Change in load configuration. Change in sterilized materials. Major maintenance work on critical instruments/elements or utilities.

Steam under Pressure:

3/19/2011 27 Steam under Pressure Sterilization by steam under pressure also is a relatively simple process which involves exposure of the product to steam at the desired temperature and pressure. The process usually is carried out in a pressure vessel designed to withstand the high temperature and pressure. To provide for uniform temperature distribution, it is important to remove the air from the sterilization chamber; this may be accompanied by gravity displacement or by a vacuum system. A vacuum system is generally preferred when compatible with the product/package system to ensure efficient air removal and optimum steam penetration.

Operational Information:

3/19/2011 28 Operational Information Autoclave Settings Temperature (F) Pressure (PSI) Time (min) General Wrapped Items 250 20 30 Bottled solutions 250 20 30 “Flashing” 270 20 4-7

Preparation for Sterilization :

3/19/2011 29 Preparation for Sterilization All instruments must be double wrapped in linen or special paper or placed in a special metal box equipped with a filter before sterilization. 'Flashing' is often used when a critical instrument is dropped. The white stripes on the tape change to black when the appropriate conditions (temperature) have been met. Indicators should be on the inside and outside of equipment pack. Expiration dates should be printed on all equipment packs.

Thank You:

T hank You