7 Autoclave Validation Gerard Sheridan

14th October 2010 Slide 1

Validation and Control of Porous Load Sterilisation

Crown Plaza Hotel, Santry; October 14th 2010

Gerard Sheridan



Overview

• Regulatory Guidance and Standards• Terminology and Definitions• Key Factors• Validation Approach

• Thermometric• Microbiological • Application of F0 concept

• Routine Monitoring• Summary



Regulatory Guidance and Standards

• EU GMP

• HTM 2010

• EN 285

• ISO 17665



• EU GMP , Annex 1

83. All sterilisation processes should be validated……

84 . …….. efficacy in achieving the desired sterilising conditions in all parts of each type of load to be processed should be demonstrated by physical measurements and by biological indicators where appropriate.

85. For effective sterilisation the whole of the material must be subjected to the required treatment and the process should be designed to ensure that this is achieved.

86. Validated loading patterns should be established for all sterilisation processes.


• HTM 2010 Part 3“Sterilization – Validation and Verification”

• ScopeA guidance document to NHSCovers a range of sterilization processesProvides validation methodology

• Longstanding source of reference

• Has served to provide a uniform basis for approach to validation and control moist heat sterilisation

• Currency?




• EN 285“STERILIZATION - STEAM STERILIZERS –LARGE STERILIZERS”

• ScopeDoes not specify requirements for the validation and routine control of sterilization by moist heat


• ISO 17665“Sterilization of health care products - Moist heat - Part 1:Requirements for the development, validation and routine control of a sterilization process for medical devices”

• ScopeMedical devices

NOTE: “Although the scope of this part of ISO 17665 is limited to medical devices, it specifies requirements and provides guidance that may be applicable to other health care products”


Terminology and Definitions

• Complete understanding of terminology• Appropriate assessment of acceptance criteria

Validity of testing!

• Uniform understanding

• Misunderstandings = Deficiencies!



Key Terminology

• Sterilization temperature• Minimum acceptable temperature of the sterilization temperature band

Therefore : Minimum temperature on which the evaluation of the sterilisation efficacy is based

• Sterilization temperature band• The range of temperatures which may prevail throughout the load during the holding

time. These temperatures are expressed as a minimum acceptable (the sterilization temperature) and a maximum allowable, and are stated to the nearest degree Celsius.

• NOTE: The temperature setting on the automatic controller will not generally be the sterilization temperature, but a higher temperature within the sterilization temperature band.


Key Terminology

• Reference measuring point (ISO)• The point where the temperature sensor used for the operating cycle control is located

The reference measurement point shall be selected in such a way that throughout the plateau period the temperature at this point correlates with the temperature in the usable space.The temperature relationship between the reference measurement point selected and the location identified as the coolest part of the usable space shall be determined.

• Chamber temperature• The lowest temperature prevailing in the chamber.

• Active chamber discharge• The controlled flow of air, or of air and condensate, from the chamber, through either

a drain or a vent, such that the temperature of the discharge is at the temperature of the chamber

• The preferred locations for monitoring are as follows:a. in the drain, if it is active throughout the operating cycle;b. otherwise in a vent, if it is active throughout the operating cycle;c. otherwise in the coldest part of the usable chamber space.


Key Terminology

• Equilibration time• The period which elapses between the attainment of the sterilization temperature in

the chamber and the attainment of the sterilization temperature in all parts of the loadNote: EU GMP, Annex 1, Paragraph 92:Sufficient time must be allowed for the whole of the load to reach the required temperature before measurement of the sterilising time-period is commenced. This time must be determined for each type of load to be processed.

• Holding time (A.K.A. Exposure time)• The period during which the temperature in all parts of the chamber and the load is

held within the sterilization temperature band. It follows immediately after the equilibration time.

• Exposure time :The period for which the process parameters are maintained within their specified tolerances.

• NOTE: The holding time / exposure time follows immediately after the equilibration time. The extent of the holding time is related to the sterilization temperature.

• Plateau period• The equilibration time plus the holding time


Key Terminology

Reference : HTM 2010 Part 3, Chapter 7, Figure 4.


Key Terminology

• THIS IS NOT A REAL DEFINITION

• Settling down period • The application of all thermometric acceptance criteria only from 60

seconds after the start of the plateau period time

• DO NOT APPLY THIS!!!

• A common misunderstanding• Thermometric test for a small load

during the plateau period the temperature measured above the test pack does not exceed the temperature measured in the active chamber discharge by more than 5ºC for the first 60 s and 2ºC for the remaining period.(Ref. HTM 2010 Part 3; 13.14 (b))

Key Factors

• Steam Quality

• Air Removal

• Load Configuration



Key Factors

• Steam Quality• Key properties to be control

Dryness >90% for normal porous loads>95% for metal loads.

Superheat<25oC of superheat

Non Condensable Gases (NCG)<3.5% NCG

Condensate QualityWFI quality when condensed


Key Factors

• Air RemovalWhilst a steam penetration test carried out on a periodic basis provides a very useful equipment control function, provision should be made to ensure adequate steam penetration occurs during every cycle.

• Air Detector• Will detect:

Poor vacuum performanceHigh chamber leak ratesHigh levels of NCG

• Various types Temperature typePressure typeElectronic Temperature/ Pressure correlation (Not appropriate)

• Set up and ‘performance tested’ as part of validation.

Key Factors

• Load Configuration

• ‘Controlled’ loading patternsRepeatable layout and orientation.

• Consider:Condensate collectionOccluded surfaces



Validation Approach

• IQ, OQ• ISO 17665

Generally references EN 285 in terms of tests to be performed.

• Commissioning • HTM 2010

Tests defined within the document Reference : HTM 2010 Part 3, Chapter 4 ‘Schedule of validation tests’

Table 2a ‘Validation tests for porous load sterilizers’ andFor each test specified the tables reference the relevant sections in which they are detailed.

In relation to Table 2a ‘Validation tests for porous load sterilizers’, note exception in relation to specified PQ test.

• NOTE: Criticality of calibrations

Validation Approach

• Performance Qualification (PQ):The process of obtaining and documenting evidence that the equipment will produce an acceptable product when operated according to process specification.

• Consists of tests designed to show that sterilization conditions are attained throughout a production load.

• Tests fall into two general categories:Thermometric tests Use accurate measuring equipment to monitor temperatures and pressures independently of the instruments fitted to the sterilizer. They provide the assurance that the temperature requirements for sterilization are met.

Microbiological testsMicrobiological tests are designed to show that sterilization conditions are attained where thermometric methodsalone are not sufficient.


Validation Approach

• Performance Qualification (PQ):• Thermometric tests• For PQ of porous loads the acceptance criteria for ‘Thermometric

test for a small load’ as specified in Section 13.14 of HTM 2010 Part 3 are to be applied.

• HTM 2010• In sterilizers with an active air removal system thermometric tests for a

‘small load’ are designed to demonstrate that the sterilizer is capable of removing air from a small load in which air from a near-empty chamber has been retained.

• Small load : ‘A specified load, used in thermometric tests, to represent the minimum size and mass of load which the sterilizer is designed to process’


Validation Approach

• Performance Qualification (PQ):• Thermometric tests

• ISO 17665 -2 • The validity of air dilution and steam penetration indirectly identified from

the performance tests specified for installation qualification and operational qualification should be verified to be effective for a worst case sterilization load, loading configuration……….

• EN 285 • The test loads described in this European Standard are selected to represent

the majority of loads…… for the evaluation of general purpose steam sterilizer for medical devices. However, specific loads (e.g. heavy metal objects or long and/or narrow lumen) will require the use of other test loads.


Validation Approach

• Acceptance criteria

• The requirements of the automatic control test are met;

• During the plateau period the temperature measured above the load does not exceed the temperature measured in the active chamber discharge by more than 5ºC for the first 60 s and 2ºC for the remaining period;

• The equilibration time determined from the measured temperatures does not exceed 15 seconds for chambers up to 800 l and 30 seconds for larger chambers;

• The holding time determined from the measured temperatures is not less than that specified for the sterilisation temperature;


Validation Approach

• Acceptance criteria

• During the holding time the temperatures measured in the active chamber discharge and in the load:

• are within the appropriate sterilization temperature band• do not fluctuate by more than ±1ºC;

NOTE: Incorrectly indicated as ±0.5ºC in some printed versions• do not differ from one another by more than 2ºC;

• during the holding time:• the indicated and recorded chamber temperatures are within 1ºC of the

temperature measured in the active chamber discharge; • the indicated and recorded chamber pressures are within 0.05 bar of the

measured pressure;


Validation Approach

• Performance Qualification (PQ):• Microbiological tests

HTM 2010• Microbiological testing may be necessary for any sterilizer where loading

conditions cannot be validated solely by thermometric methods.

ISO 17665 -2 • Data from which judgement is to be made should be established from

temperature measurements supplemented by chemical indicators and/or biological indicators positioned in difficult-to-sterilize locations.


Validation Approach

• Performance Qualification (PQ):• Microbiological tests

• Biological Indicators (BIs)• Ph.Eur.

5.1. 2. BIOLOGICAL INDICATORS OF STERILISATIONSteam sterilisation. The use of biological indicators intended for steam sterilisation is recommended for the validation of sterilisation cycles. Spores of Bacillus stearothermophilus (for example, ATCC 7953, NCTC 10007, NCIMB 8157 or CIP 52.81) are recommended. The number of viable spores exceeds 5 × 105 per carrier. The D-value at 121 °C exceeds 1.5 min.


Validation Approach

• Performance Qualification (PQ):

• In principle, PQ is required for each loading configurationMin / Max approach acceptable

• PQ shall include a series of at least three consecutive exposures of the sterilization load to the sterilization process, which demonstrate compliance with the sterilization process specification and the reproducibility of the sterilization process.


Application of F0 concept

• HTM 2010The F0 method may be used for assessment, or control, of processes where difference in temperature is the only factor influencing the efficacy of the cycle. For example, it may be applied to the steam sterilization of aqueous fluids in sealed containers but it is not applicable to steam sterilization of porous loads where air removal is also a key factor and failure to achieve direct contact with Dry Saturated Steam can lead to failure, regardless of whether the required temperature was achieved within the load.

• ISO 17665-2If a medical device is wrapped and/or non-condensable gas can be trapped in a part such as a lumen, tubing or crevice, F0 calculated from chamber temperatures will not represent the lethality delivered and should not be used to judge the results of a sterilization process……..In addition to the measurement of process parameters, steam penetration should be assured for each operating cycle, for example, by using an air detector fitted to the sterilizer


Routine Monitoring and Control

• Periodic tests

• Must be subject to a schedule of periodic tests at various levels and intervals• Daily, • Weekly,• Quarterly • Yearly

The yearly test schedule is essentially a revalidation schedule. It provides for performance requalification (PRQ) tests to confirm that data collected during performance qualification remain valid.

• Appropriate schedule:Reference HTM 2010 Part 3, Chapter 5, Table 4a ‘Periodic tests for porous load sterilizers’



• Controls

• Roles and responsibilities clearly defined

• Personnel appropriately trained and assessed

• Stringent maintenance and calibration programmes

• Control of external contractors

• Change control

• Review and approval of each cycle• Documented procedure in place




• Controls

• Microbiological status of parts

• Validation and routine control of any cleaning procedures used on parts

• Control of the environment in which parts are assembled / wrapped

• The materials in which parts are wrapped and the manner in which they are wrapped

• Conditions under which parts are stored


Summary

• Understand the fundamentals

• Be familiar with relevant standards

• Have appropriate quality steam

• Have a well defined and planned validation approach

• Implement rigorous controls




Questions?

Documents

7 Autoclave Validation Gerard Sheridan