EN/ISO 11737-2 “Sterilization of health care products – Microbiological

methods – Part 2: Tests of Sterility performed in the definition, validation

and maintenance of a sterilisation process’’
Note on differences between 2009 and 2019 versions

Introduction
An updated version of document EN/ISO 11737-2 “Sterilization of health care products –
Microbiological methods – Part 2: Tests of Sterility performed in the definition, validation and
maintenance of a sterilisation process’” was published in 2019, replacing the version that had been
published in 2009.

Although the Scope and overall outline of the two documents are similar, there have been some
changes in terms of terminology, more detailed guidance in appendices and a new Annex B.

The purpose of this document is to highlight, in general terms, areas of difference between the two
versions of the standard.
Contents of 11737-2:2019
Figure 1 : Content page of ISO11737-2:2019 and ISO 11737-2 :2009 for comparison

Figure 1 shows the contents of 11737-2:2019 and 2009. The overall structure is very similar to that of 11737-2:2009, but Sections have been renamed and
restructured.

One new informative Annex has been added: Annex B Typical alignment of responsibilities.

In the remainder of this document, differences between the two standards will be given, using the numbering and titles of clauses in 11737-2:2019.
The Foreword lists the following summary of changes :

Introduction
More clarity has been included here on the use of fractional exposure/verification doses and their
intent. Item c has been added and the final paragraph express that performing a test of sterility on a
product that has been exposed to the complete sterilisation process provides no scientifically usable
data and is not recommended.

Extract :
Scope (Clause 1)
The Scope introduces the term ‘healthcare product’ to replace the term ‘medical device’ – this
continues throughout the document.

Clarity added on what this document is NOT applicable to.

Additional references added ISO 20867, ISO 11737-2 itself.

Addition of ‘… not applicable to…c) test of sterility or test for sterility for demonstration of product shelf
life, stability and/or package integrity..’

Normative References (Clause 2)

All removed as compared from the 2009 version.

Terms and Definitions (Clause 3)

This Clause introduces some new terms: namely aseptic technique / health care product / method
suitability and removes aerobic organism, anaerobic organism, growth promotion test.

General (Clause 4)
Title changed from 'quality management system elements'

Section condensed from 2009 but no change to intent.

Selection of products (Clause 5)

Section has additional wording but no change to intent. Reference added to ‘product family’.
Added 5.1.3 : ‘The rationale for the number of product items that are selected and the number of
batches from which this selection is made shall be documented.’

Added note in 5.2.2.1 : ‘When selecting the portion that contains the most severe microbial
challenge, the relationship of the bioburden of the SIP tested to the entire product bioburden should
be established.’
Added note about calculation of SIP. Table of SIP calculation moved to Annex A.

Methods for performing tests of sterility (Clause 6)

Added a third method to the list of options ; direct immersion, removal of organisms, filtration of liquid
products.

Added wording in 6.1a) ‘The product shall be immersed in the culture media for the duration of the
incubation time where possible. A rationale shall be provided if this is not possible, such as with
buoyant materials.’

Added 6.4 b) ‘Establishment of a recovery efficiency followed by a risk assessment to determine the
appropriateness of the removal process’.

Added wording to 6.6 and introduction of the wording ‘method suitability’; ‘The test system shall be
evaluated in a method suitability test (also called bacteriostasis / fungistasis) to ensure that the ability
to sustain microbiological growth is not affected.’
Assessment of the method for performing tests of sterility (Clause 7)
No significant changes.

Maintenance of the method for performing tests of sterility (Clause 8)

Added wording to 8.2, ‘ Modifications to the parameters of a test of sterility’… shall be assessed..

Annex A
In general more detail added in the guidance sections.

A.1 Scope

A.1.2 Addition: ‘tests for sterility are excluded from this document because they
are not performed in the definition, validation and maintenance of a
sterilisation process. Tests for sterility are not appropriate for confirmation
of a sterilisation process effectiveness, a sterility assurance level, or
attributes associated with the sterility of a product such a package integrity
or product shelf life.’

A.5 Selection of product

A.5.2.1 Addition: ‘this might not be feasible if the product cannot be accommodated
in available laboratory testing vessels’. ‘If a product cannot be tested in
available laboratory containers, it may be divided into two or more
containers and these containers scored together as one, if one container
yields a positive result, the entire product item is considered positive’.
A.5.2.2 Addition: ‘as large a portion of the product as possible should be used for
SIP… Consideration should be given to aspects of manufacturing that
contribute to the distribution of microorganisms on product.’
‘Product such as drapes, lengths of tubing, etc. are types of product that
couldbe expected to have an even distribution of bioburden. This might not
apply in case of application of manual steps for cutting or folding of drapes
as well as for cutting, transportation, and assembly of tubing.’
A.5.2.3 Addition: Examples of an SIP that can be selected from the device with a
more severe challenge to the sterilisation process are tubing sets with
connections, stopcocks etc. Additional examples have been added to table
A.1.
A.5.3 No change

A.6 Methods of performing tests of sterility

A.6.1 a) Addition of statement: ‘ if this is not possible due to the buoyant nature of
the product, a procedure should be implemented to periodically manipulate
the container so that contact is facilitated during the incubation period.’
b) Addition of : ‘as elution of microorganisms form product is often not as
effective for a test of sterility compared to direct immersion. Therefore
 direct immersion methods are preferable whenever practicable. If the direct
immersion method is not practicable an elution method can be considered.
In the elution methods, an understanding of the recovery efficiency coupled
with a risk assessment and rationale is critical.
A.6.2 NEW : Guidance on when packaging material is included in the test of
sterility and consideration for the contact with culture media.
A.6.3 Addition : ‘conducting the test in a laminar flow hood, micro safety cabinet,
or other equipment ensuring the same particulate and microbiological level,
within a microbiologically controlled room or in barrier isolation in a
microbially controlled environment. Ref ISO 14644 / 14698.’
Addition : minimising the amount of materials in the hood,
Addition : ‘taking care not to disrupt the airflow patterns during
manipulation’.
A.6.4 Addition: ‘ …performing an elution of product by directly culturing…’
A.6.5 Addition: ‘…with the aid of vacuum or pressure..’
A.6.6 Addition: ‘…is called the method suitability test (also called bacteriostasis /
fungistasis test’
Addition : ‘Microbicidal substances can bind to filter membranes, care
should be taken to ensure the use of suitable filter membranes to minimise
the potential for binding’
Addition : ‘Guidance on the procedures, organisms, titers and incubation
times for method suitability can be found in current Pharmacopeias.
However the incubation temperature and culture media have to be the
same as those used in performing the tests of sterility.’
Addition : ‘ Multiple attempts should be made using different culturing
conditions to eliminate or reduce inhibitory substances to the point where
there is no longer an acceptable risk. After multiple attempts are made, if
the inhibitory substance is not eliminated, it is appropriate to accept a
reduction of inhibitory substances, with an accompanying rationale and risk
assessment.’
A.6.7 Addition: …’e.g the presence of anaerobes or mycobacteria.’
A.6.9 Addition: …’ and colour change. Generally, when product items are positive
for microbial growth, the microorganism(s) should be identified.

A.7 Assessment of method for performing tests of sterility.

A.7 Addition : ‘Factors which might affect the occurrence of false positives
include: breach in the sterile barrier, contamination during testing,
contamination from handling during incubation’
Addition : ‘The occurrence of false negatives in tests of sterility can affect the
interpretation of data obtained in validation by making a treatment with the
sterilising agent more effective.’
Addition : … allowing for microorganisms to lose viability’.
Addition : ‘If the occurrence of positive tests of sterility can be ascribed to
incorrect performance of the tests of sterility, a sterilising agent related issue
 or another relevant cause , corrective action can be implemented and a
repeat test of sterility can be performed.

A.8 Maintenance of the method for performing tests of sterility.

A.8.1 Addition: ‘Because the test of sterility is vital to support definition, validation
and maintenance of a sterilisation process for a product or product family, a
change to product, the processes used to manufacture product, sterilisation
process or to the parameters of the test of sterility, necessitates
consideration of the need to demonstrate ongoing method suitability.
Consideration should be given to the effects of cumulative changes over
time. Changes to the test of sterility should be carried out within a
documented change control process’.
Addition : ‘Even in the absence of planned changes to product , the
processes used to manufacture product or to the parameters to the tests of
sterility, consideration should be given to periodically reviewing ongoing
method suitability to ensure that an accumulation of minor changes over
time has not occurred that could adversely affect the continued suitability of
the test method.’

Annex B
Annex B Addition: New Annex regarding assignment of responsibilities