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Regulations & Legislation

ISO 11137 – Requirements for the Validation and Routine Control of

Radiation Sterilization of Healthcare Products – A Discussion of
a report by Current Revisions
John Harries

UK Expert to WG2 and WG8, International Organization for Standardization (ISO)

There are currently two standards that regulate the
sterilisation of healthcare products using ionising
radiation – the European Standard (EN) 5521 published
in 1994 and International Organization for
Standardization (ISO) 111372 published in 1995. These
two standards are very similar in their requirements;
however, ISO 11137 contains more detail with regard
to dose setting methods.
Both standards are currently being revised and will be
combined into a new standard ISO EN 11137. This
article will summarise the major changes that are
likely to be incorporated in the new standard. It must
be emphasised that this article references requirements
that are currently in a draft form and have not been
published. There is therefore a possibility that some of
the content discussed in this article may change in the
final form of the published standard.
The new combined draft standard is a three-
part document:
Part 1 – Requirements for the
Development, Validation and Routine
Control of a Sterilization Process for
Medical Devices
There are nine sections to Part 1, which is
normative. In addition, there is an Annexe A, which
contains guidance to each requirement where
available. The key changes are as follows.
• Increased emphasis on the establishment of
maximum acceptable dose. The standard suggests
that a test programme shall be undertaken to
establish the effect on product of treatment with a
wide range of doses.
• Although the requirement to reference a
maximum dose exists in the current standards the
addition of the need to undergo a test programme
will undoubtedly lead to increased costs in the
development of new products.
John Harries is the UK Expert to
WG2 and WG8 of the International
Organization for Standardization
(ISO), which is developing the new
combined European Standard (EN)
552/ISO 11137 Standard for
Control and Validation of
Sterilization of Healthcare Products
using Ionising Radiation. He is also
Corporate Quality Compliance
Manager for Isotron plc. He spent
seven years with a medical device/
microbiological diagnostic
manufacturer where, as the
laboratory manager, he was
responsible for quality assurance
(QA) and research and development
(R&D). He is an active member of
the Association of British Healthcare
Industries (ABHI) Sterilization
Working Group and Chairman of
the Microbiology Group of the
Panel on Gamma and Electron
irradiation. Mr Harries is also a
member of British Standards
Institution (BSI) Sterilization
Standards Committee CH/67.

• Part 1 – Requirements for the Development,
Validation and Routine Control of a Sterilization
Process for Medical Devices;
• Part 2 – Establishing the Sterilization Dose for
Radiation Sterilization; and
• Part 3 – Guidance on Dosimetric Aspects.
The format and style of the standard has changed
significantly. The new standard is based on ISO
14937: 2000 – Sterilization of Healthcare Products –
General Requirements for Characterization of a
Sterilizing Agent and the Development, Validation
and Routine Control of a Sterilization Process for
Medical Devices. This ‘umbrella’ standard is
intended to be used for the regulation of any new or
novel sterilisation techniques; however, it is also
being used as the format for the revision of all three
major sterilisation technology standards, i.e. ethylene
oxide, radiation and moist heat.
• There is more detailed reference to the
application of X-rays to sterilise healthcare
products in this draft standard. This underlines the
increasing importance of this technology in the
field of healthcare sterilisation.
• The transfer of dose between different radiation
technologies has more emphasis and greater clarity
in the new standard. There are specific
requirements laid down for the transference of
maximum acceptable, verification and sterilisation
dose between radiation sources. A distinction is
made between products containing water and
products that do not contain water.
• The new standard contains much more emphasis
on product definition. There are sections within
the requirements regarding the use of product
families for establishing the sterilisation dose and
dividing into product categories for the purpose
of routine processing. This will enable

1. BS EN 552, “Sterilization of Medical Devices – Validation and Routine Control of Sterilization by Irradiation” (1994).
2. ISO 11137, “Sterilization of Health Care Products – Requirements for Validation and Routine Control – Radiation
Sterilization” (1995). 23

BUSINESS BRIEFING: MEDICAL DEVICE MANUFACTURING & TECHNOLOGY 2005

Harries.qxp 17/5/05 12:26 pm Page 24
Regulations & Legislation
validation cost savings; however, there is set
criteria that must be followed to ensure
compliance with the standard.
• The section on validation in the new standard is
now divided into three distinct stages:
– installation qualification (IQ),
– operational qualification (OQ) and
– performance qualification (PQ).
• The need to perform quarterly dose audits
required by the current standards has caused
problems for many medical device manufacturers
primarily due to the availability and cost of
product and the volume of microbiological
testing involved. This has been recognised by the
standards committee and greater flexibility has
been introduced.
• A completely new section, The Maintenance of
Process Effectiveness, covers bioburden determ-
ination and sterilisation dose audits. This
provides an opportunity to reduce the frequency
of dose audits when combined with regular
bioburden determination and successful periodic
dose audits.
• It is possible to reduce the microbiological
monitoring required to a bioburden determ-
ination every quarter and a sterilisation dose audit
annually within three years provided dose audits
are successful and bioburden determinations are
within specification. However, for products with
low bioburden there is a need to perform monthly
bioburden determinations.
Part 2 – Establishing the
Sterilization Dose for Radiation
Sterilization
This provides guidance on the establishment of
sterilisation dose and is considered informative.
However, if a decision is made to follow one of the
methods it becomes normative with respect to
the methodology.
The main change is the addition of VDmax3 for the
substantiation of 25kGy and 15kGy as a sterilising
dose. The specific method for the substantiation is in
addition to Method 1 and Method 2, which are
carried forward from the current ISO 11137.
The method for VDmax utilises only 40 product
units as opposed to 130 for a Method 1 or 840 for
3. Kowalski J, Tallentire, “A Substantiation of 25 kGy as a Sterilization Dose: A Rational Approach to Establishing
Verification Dose”, Radiat. Phys. Chem. (1999);54; pp. 55–64.
24 4. Herring, C, “Dose Audit Failures and Dose Augmentation”, Radiat. Phys. Chem. (1999);54; pp 77–81.
BUSINESS BRIEFING: MEDICAL DEVICE MANUFACTURING & TECHNOLOGY 2005
a Method 2. The verification dose is set at a sterility
assurance level (SAL) of 10-1 not 10-2 as in Method
1 and the pass criteria is one failure in 10 sterility
tests. Both VDmax methods will only substantiate
a minimum dose to achieve a sterility assurance
level of 10-6.
The table of radiation dose required to achieve a
given SAL for an average bioburden utilised in
Method 1 has changed significantly. The table now
starts at 0.1 average bioburden, which is a higher
bioburden than the current table, and the table in
the draft now references bioburden value to one
decimal place to a bioburden of 10 and thereafter
whole numbers of bioburden. This should make
the table easier to use and is a more logical method
of representing the data. This will change the
average bioburden that equates to the minimum
sterilisation dose, e.g. in the new table the average
bioburden equivalent to a minimum dose of 25
kGy for an SAL 10-6 is now 1,100.
The draft also contains a different method of dealing
with dose augmentation. Dose augmentation is
required when a dose audit fails. It is based on a
method that utilises extrapolation, which is linked to
the number of audit sterility test failures.
This method of augmentation of the sterilisation
dose, established using Methods 1, Method 2A or
Method 2B is based on a method propounded by
Herring in 1999.4 It uses the information from the
failed dose audit and the principles underlying
Method 2, together with a conservative estimate of
the resistance of the most radiation-resistant
component of the microbial population contam-
inating the product. The draft standard also
recognises that the cause of the dose audit failure
often cannot be identified. It contains a statement
that it is not possible to assess the extent to which the
SAL of previously sterilised batches has been affected.
Augmentation of the dose should begin with the
next batch to be sterilised and no action should be
taken with previously released batches.
Part 3 – Guidance on
Dosimetric Aspects
This gives useful guidance on dosimetry used in the
measurement of absorbed dose during radiation
sterilisation. Part 3 is informative.
There are sections on the measurement of dose
establishing the maximum acceptable and sterilising
dose, selection and calibration of dosimetry systems,
Harries.qxp 17/5/05 1:25 pm Page 25

ISO 11137 – A Discussion of Current Revisions

installation qualification, operational qualification distribution provided by mathematical modelling can

and performance qualification. be used to ensure that a sufficient number of
dosimeters are distributed in the expected zones for
There is also an annex A to Part 3 that details minimum and maximum doses during irradiator dose
mathematic modelling. Mathematic modelling may mapping studies.
be used to estimate doses in certain applications.
There are a number of methods for mathematical The use of mathematical modelling in industrial
modelling of radiation transport; however, most irradiators is relatively new but there is increased
modelling is performed using either the Point Kernel interest in these techniques and it is predicted that
Method or the Monte Carlo Method. it will have more prominence in the future.

The Point Kernel Method is used for calculating Conclusion

the dose distribution in gamma and X-ray
irradiators, while the Monte Carlo Method can The revision process for this standard is now ending.
be used for gamma, X-ray and electron It is anticipated the final draft ISO (F-Dis) will be
beam irradiators. issued in June or July 2005 with publication of the
final standard early in 2006. There will be a three-year
Mathematical modelling is used extensively in the transitional period for implementation of the
design of irradiators. Calculations are performed to requirements of the standard. This will allow
optimise the irradiation geometry to achieve the manufacturers, contract sterilisers and regulatory
desired throughputs and dose homogeneity. Data authorities time to ensure effective implementation.
from mathematical modelling is used to determine
the radiation performance of the irradiator when The new standard will provide clarification of many
filled with homogeneous product. issues related to sterilisation of healthcare products
using ionising radiation. However, medical device
Mathematical modelling can also be used in manufacturers should be aware that it will present
conjunction with dose mapping. For gamma some challenges to ensure compliance with the
irradiators, information on the expected dose requirements of the new combined standard. ■

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