EQUIPMENT EQUIPMENT VALIDATION - VALIDATION -

Autoclave Autoclave

Dr. L . PrabakaranDr. L . PrabakaranProf. & HeadProf. & Head

R. R. College of PharmacyR. R. College of PharmacyBangalore -90.Bangalore -90.

History of ValidationHistory of Validation

1970’s- The term validation 1970’s- The term validation started gaining attentionstarted gaining attention

1980’s –Process validation is here 1980’s –Process validation is here to stay- FDA Books on Process to stay- FDA Books on Process validation started appearingvalidation started appearing

1990’s – Emphasis on Validation1990’s – Emphasis on Validation Current – As a Current – As a GMPGMP concept concept

IntroductionIntroduction Next to GMP, Validation is most used term Next to GMP, Validation is most used term

today and has become a catchy word.today and has become a catchy word.

Validation is no more a high sounding word. It Validation is no more a high sounding word. It has become reality and part and parcel of GMP.has become reality and part and parcel of GMP.

Validation makes the life livelier.Validation makes the life livelier.

Today the term is defined in the law. Today the term is defined in the law.

New New Schedule MSchedule M deals with it. deals with it.

Validation is one which has been proved to Validation is one which has been proved to do what it purports to do.do what it purports to do.

The proof of Validation is obtained through The proof of Validation is obtained through collection and evaluation of the data collection and evaluation of the data preferably beginning from the process.preferably beginning from the process.

Validation is documented common sense.Validation is documented common sense.

Reasons for ValidationReasons for Validation

Quality AssuranceQuality Assurance EconomicsEconomics Reduction in the cost associated Reduction in the cost associated

with process monitoring sampling with process monitoring sampling and testingand testing

Qualify the goals towards Qualify the goals towards Parametric release Decrease or Parametric release Decrease or eliminate product rejectionseliminate product rejections

Compliance - Compliance - FDA’s requirementFDA’s requirement

Means a written plan stating how validation Means a written plan stating how validation will be conducted, including test will be conducted, including test parameters, product characteristics, parameters, product characteristics, production equipment, and decision points production equipment, and decision points on what constitutes acceptable test results.on what constitutes acceptable test results.

Validation Validation ProtocolProtocol

AutoclaveAutoclave Autoclaves use pressurized steam to destroy Autoclaves use pressurized steam to destroy

microorganisms, and are the most dependable microorganisms, and are the most dependable systems available for the decontamination of systems available for the decontamination of laboratory waste and the sterilization of laboratory waste and the sterilization of laboratory glassware, media, and reagents. laboratory glassware, media, and reagents.

Autoclaves should be tested periodically with Autoclaves should be tested periodically with biological indicators biological indicators like cultures of like cultures of Bacillus Bacillus stearothermophilus stearothermophilus to ensure proper function. to ensure proper function.

This method of sterilization works well for many This method of sterilization works well for many metal and glass items but is not acceptable for metal and glass items but is not acceptable for rubber, plastics, and equipment that would be rubber, plastics, and equipment that would be damaged by high temperatures damaged by high temperatures

Autoclave

Autoclaves, or steam sterilizers essentially consist of Autoclaves, or steam sterilizers essentially consist of following: following:

i) A cylindrical or rectangular chamber, with i) A cylindrical or rectangular chamber, with capacities ranging from 400 to 800 liters. capacities ranging from 400 to 800 liters.

ii) Water heating system or steam generating system ii) Water heating system or steam generating system

iii) Steam outlet and inlet valves iii) Steam outlet and inlet valves

iv) Single or double doors with locking mechanism. iv) Single or double doors with locking mechanism.

v) Thermometer or temperature gauge v) Thermometer or temperature gauge

vi) Pressure gauges vi) Pressure gauges

For porous loads (dressings) sterilizers are For porous loads (dressings) sterilizers are generally operated at a minimum generally operated at a minimum temperature of temperature of 13413400CC, and for bottled fluid, , and for bottled fluid, sterilizers employing a minimum sterilizers employing a minimum temperature of temperature of 12112100CC are used. are used.

Ensure that there should be sufficient water Ensure that there should be sufficient water in the autoclave to produce the steam. in the autoclave to produce the steam.

The stages of operation of autoclaves include The stages of operation of autoclaves include air removal, steam admission and air removal, steam admission and sterilization cycle (includes heating up, sterilization cycle (includes heating up, holding/exposure, and cooling stages). holding/exposure, and cooling stages).

OperationOperation

AUTOCLAVE VALIDATION – WHAT IS AUTOCLAVE VALIDATION – WHAT IS REALLY REQUIRED?REALLY REQUIRED?

Load TypesLoad Types

Autoclaves are used to sterilize several different types Autoclaves are used to sterilize several different types of loads:of loads:

Solid Solid – metal, glass, plastic– metal, glass, plastic

PorousPorous – linen, gowns, paper, gauze, – linen, gowns, paper, gauze, complex complex instruments, hollow tubesinstruments, hollow tubes

LiquidLiquid – water, saline, media – water, saline, media

Laboratory waste Laboratory waste – Petri dishes, sample bottles, – Petri dishes, sample bottles, syringessyringes

System suppliesSystem supplies Most autoclaves are electrically powered and all Most autoclaves are electrically powered and all

steam autoclaves require some form of a water steam autoclaves require some form of a water supply to produce steam.supply to produce steam.

The electrical supply must be able to handle the The electrical supply must be able to handle the maximum peak power of the autoclave.maximum peak power of the autoclave.

The drainage system must be able to handle The drainage system must be able to handle the maximum flow of water and condensate the maximum flow of water and condensate and should be able to tolerate and should be able to tolerate 100 °C100 °C..

CommissioningCommissioningCommissioning tests should include checking:Commissioning tests should include checking:

that the electrical supply is suitable for the autoclavethat the electrical supply is suitable for the autoclave

that the temperature and humidity are sufficiently well that the temperature and humidity are sufficiently well controlledcontrolled

that there is no interference to or from other that there is no interference to or from other equipmentequipment

the accuracy of indicators has been certified to national the accuracy of indicators has been certified to national standardsstandards

the temperature and pressure of the chamber the temperature and pressure of the chamber during a sterilization cycle are within during a sterilization cycle are within specificationsspecifications

the leakage into the chamber during a vacuum the leakage into the chamber during a vacuum

cycle does not exceed the specified maximumcycle does not exceed the specified maximum

that there is no leakage of steam, water or that there is no leakage of steam, water or effluent at any point during the sterilization effluent at any point during the sterilization cyclecycle

Routine CheckingRoutine Checking Routine checking may be broken down into Routine checking may be broken down into

daily, weekly, quarterly and annual checks.daily, weekly, quarterly and annual checks.

Daily checks should be performed by the Daily checks should be performed by the operator and should include the observation operator and should include the observation of all indicators for “normal” values.of all indicators for “normal” values.

On a weekly basis safety checks should be On a weekly basis safety checks should be performed such as inspection for leaks and performed such as inspection for leaks and electrical wiring faults, inspection of door electrical wiring faults, inspection of door seals, correct of operation of door interlocks seals, correct of operation of door interlocks and high temperature and low water alarms.and high temperature and low water alarms.

Routine checking may be broken down into daily, Routine checking may be broken down into daily, weekly, quarterly and annual checks.weekly, quarterly and annual checks.

Daily checks should be performed by the operator Daily checks should be performed by the operator and should include the observation of all indicators and should include the observation of all indicators for “normal” values.for “normal” values.

On a weekly basis safety checks should be On a weekly basis safety checks should be performed such as inspection for leaks and electrical performed such as inspection for leaks and electrical wiring faults, inspection of door seals, correct of wiring faults, inspection of door seals, correct of operation of door interlocks and high temperature operation of door interlocks and high temperature and low water alarms.and low water alarms.

DocumentationDocumentation

The results of all commissioning tests The results of all commissioning tests and performance qualification tests and performance qualification tests should be fully recorded, reviewed, should be fully recorded, reviewed, accepted and archived by the relevant accepted and archived by the relevant personnel in the organization that uses personnel in the organization that uses the autoclave.the autoclave.

Heat distribution studies:Heat distribution studies: The intent of this study is to The intent of this study is to demonstrate the demonstrate the

temperature uniformity & stability of the sterilizing of temperature uniformity & stability of the sterilizing of the sterilizing medium throughout the sterilizerthe sterilizing medium throughout the sterilizer. .

Temperature distribution studies should be conducted Temperature distribution studies should be conducted on both the on both the emptyempty and and loaded chambersloaded chambers, with , with maximummaximum & & minimum load configurationsminimum load configurations. .

A narrow temperature uniformity range is required, A narrow temperature uniformity range is required, generally variation of generally variation of less than ±1ºCless than ±1ºC of the mean of the mean chamber temperature. chamber temperature.

If equipment is to be used in the terminal sterilization If equipment is to be used in the terminal sterilization of products uniformity of of products uniformity of ±0.5ºC±0.5ºC of the mean is of the mean is desirable.desirable.

Object mapping;Object mapping;

The study includes The study includes determination of slowest determination of slowest to heat zone to heat zone within an object such as filter within an object such as filter housings, hoses, containers filled with the housings, hoses, containers filled with the stoppers.stoppers.

Heat penetration studies;Heat penetration studies;

the intent of the study is to the intent of the study is to determine the determine the coolest points coolest points within a specified load & within a specified load & configuration.configuration.

Microbiological challenge studies:Microbiological challenge studies:

Biological castles are employed during heat Biological castles are employed during heat penetration situations in order to penetration situations in order to demonstrate the degree of process lethality demonstrate the degree of process lethality provided by the sterilization cycle. provided by the sterilization cycle.

Calibrated Calibrated biological indicators biological indicators utilized are utilized are bacillus stearothermophilus & clostridium bacillus stearothermophilus & clostridium sporogenes, spore-forming bacteria because sporogenes, spore-forming bacteria because of their relatively high heat resistance.of their relatively high heat resistance.

MONITORING STERILIZATION MONITORING STERILIZATION PROCEDURESPROCEDURES

Sterilization procedures can be monitored Sterilization procedures can be monitored routinely using a combination of biological, routinely using a combination of biological, chemical and mechanical indicators as chemical and mechanical indicators as parameters.parameters.

Biological IndicatorsBiological Indicators

Monitoring the sterilization process with reliable Monitoring the sterilization process with reliable biological indicators at regular intervals is biological indicators at regular intervals is strongly recommended. strongly recommended.

Measurements should be performed with a Measurements should be performed with a biological indicator that employs spores of biological indicator that employs spores of established resistance in a known population. established resistance in a known population.

Chemical IndicatorsChemical Indicators Chemical indicators include indicator tape or Chemical indicators include indicator tape or

labels, which monitor time, temperature and labels, which monitor time, temperature and pressure for steam sterilization, and time and pressure for steam sterilization, and time and temperature for dry-heat sterilization. temperature for dry-heat sterilization.

These indicators should be used on the inside These indicators should be used on the inside and outside of each package or container.and outside of each package or container.

External indicators External indicators are used to verify that items are used to verify that items have been exposed to the correct conditions of have been exposed to the correct conditions of the sterilization process and that the specific the sterilization process and that the specific pack has been sterilized. pack has been sterilized.

Internal indicators Internal indicators are placed inside a pack or are placed inside a pack or container in the area most difficult for the container in the area most difficult for the sterilization agent to reach. This is the indicator sterilization agent to reach. This is the indicator that tells if the item has been sterilized. that tells if the item has been sterilized.

Dry Heat Sterilization Dry Heat Sterilization

IndicatorsIndicators PrinciplePrinciple DeviceDevice Parameter Parameter monitoredmonitored

ChemicalChemical Temperature Temperature sensitive sensitive colored solutioncolored solution

Browne’s tubeBrowne’s tube Temperature, Temperature, timetime

Temperature Temperature sensitive sensitive chemicalchemical

A temperature A temperature sensitive white sensitive white wax concealing a wax concealing a black markedblack marked

TemperatureTemperature

BiologicalBiological Temperature Temperature sensitive sensitive microbesmicrobes

Bacillus subtilisBacillus subtilis D valueD value

Moist Heat SterilizationMoist Heat Sterilization

IndicatorsIndicators PrinciplePrinciple DeviceDevice Parameter Parameter monitoredmonitored

ChemicalChemical Temperature Temperature sensitive colored sensitive colored solutionsolution

Browne’s tubeBrowne’s tube Temperature, Temperature, timetime

Steam sensitive Steam sensitive chemicalchemical

A device which A device which is impregnated is impregnated into a carrier into a carrier materialmaterial

Saturated Saturated steamsteam

BiologicalBiological Temperature Temperature sensitive microbessensitive microbes

Bacillus Bacillus StearotherophilStearotherophilusus

D valueD value