Validation and Control of

Porous Load Sterilisation

Crown Plaza Hotel, Santry; October 14th 2010

Gerard Sheridan

14th October 2010 Slide 1

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14th October 2010 Slide 3
 Overview

• Regulatory Guidance and Standards

• Terminology and Definitions
• Key Factors
• Validation Approach
• Thermometric
• Microbiological
• Application of F0 concept
• Routine Monitoring
• Summary
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 Regulatory Guidance and Standards

• EU GMP

• HTM 2010

• EN 285

• ISO 17665

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 Regulatory Guidance and Standards

• 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.

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 Regulatory Guidance and Standards

• HTM 2010 Part 3

“Sterilization – Validation and Verification”
• Scope
ƒ A guidance document to NHS
ƒ Covers a range of sterilization processes
ƒ Provides validation methodology

• Longstanding source of reference

• Has served to provide a uniform basis for approach to validation and

control moist heat sterilisation

• Currency?

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 Regulatory Guidance and Standards

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

• Scope
ƒ Does not specify requirements for the validation and routine
control of sterilization by moist heat

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 Regulatory Guidance and Standards

• 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”

• Scope
ƒ Medical devices
ƒ 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”

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 Terminology and Definitions

• Complete understanding of terminology

• Appropriate assessment of acceptance criteria
ƒ Validity of testing!

• Uniform understanding

• Misunderstandings = Deficiencies!

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 Key Terminology

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

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 Key Terminology

• Reference measuring point (ISO)

• The point where the temperature sensor used for the operating cycle control is located
ƒ 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.
ƒ 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:
ƒ a. in the drain, if it is active throughout the operating cycle;
ƒ b. otherwise in a vent, if it is active throughout the operating cycle;
ƒ c. otherwise in the coldest part of the usable chamber space.

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 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 load
ƒ Note: 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

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 Key Terminology

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

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 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
ƒ 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))

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 Key Factors

• Steam Quality

• Air Removal

• Load Configuration

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 Key Factors

• Steam Quality
• Key properties to be control

ƒ Dryness
ƒ >90% for normal porous loads
ƒ >95% for metal loads.
ƒ Superheat
ƒ <25oC of superheat
ƒ Non Condensable Gases (NCG)
ƒ <3.5% NCG
ƒ Condensate Quality
ƒ WFI quality when condensed

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 Key Factors

• Air Removal
Whilst 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:
ƒ Poor vacuum performance
ƒ High chamber leak rates
ƒ High levels of NCG
• Various types
ƒ Temperature type
ƒ Pressure type
ƒ Electronic Temperature/ Pressure correlation (Not appropriate)

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

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 Key Factors

• Load Configuration

• ‘Controlled’ loading patterns

ƒ Repeatable layout and orientation.

• Consider:
ƒ Condensate collection
ƒ Occluded surfaces

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 Validation Approach

• IQ, OQ
• ISO 17665
ƒ Generally references EN 285 in terms of tests to be performed.

• Commissioning
• HTM 2010
ƒ Tests defined within the document
ƒ Reference : HTM 2010 Part 3, Chapter 4 ‘Schedule of validation tests’
ƒ Table 2a ‘Validation tests for porous load sterilizers’ and
ƒ For each test specified the tables reference the relevant sections in
which they are detailed.

ƒ In relation to Table 2a ‘Validation tests for porous load sterilizers’,

note exception in relation to specified PQ test.

• NOTE: Criticality of calibrations

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 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:

ƒ 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.

ƒ Microbiological tests
Microbiological tests are designed to show that sterilization
conditions are attained where thermometric methods
alone are not sufficient.

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 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’

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 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.

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 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;

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 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;
ƒ 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;

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 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.

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 Validation Approach

• Performance Qualification (PQ):

• Microbiological tests

• Biological Indicators (BIs)

• Ph.Eur.
5.1. 2. BIOLOGICAL INDICATORS OF STERILISATION
ƒ Steam 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.

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 Validation Approach

• Performance Qualification (PQ):

• In principle, PQ is required for each loading configuration

ƒ Min / 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.

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 Application of F0 concept

• HTM 2010
The 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 17665-2
If 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

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 Routine Monitoring and Control

• Periodic tests

• Must be subject to a schedule of periodic tests at various levels and intervals

• Daily,
• Weekly,
• Quarterly
• Yearly
ƒ 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’

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 Routine Monitoring and Control

• 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

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 Routine Monitoring and Control

• 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

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 Summary

• Understand the fundamentals

• Be familiar with relevant standards

• Have appropriate quality steam

• Have a well defined and planned validation approach

• Implement rigorous controls

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 Questions?

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