Radiation Sterilization Standards, such as ISO 11137 and related Technical Reports and Specifications pertaining to radiation sterilization of medical products were discussed. Standard

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1

Abhaya Sharma

ISOMED, Bhabha Atomic Research Centre

Trombay, Mumbai, 400 085 India

(Email: abhaya@magnum.barc.ernet.in)

Introduction

Radiation sterilization using

gamma radiation from Cobalt-60 or

Caesium-137 has achieved a

phenomenal success in the last three

decades or so. The method offers

several advantages over the traditional

methods of sterilization viz. ethylene

oxide, dry and moist heat.

The major advantages include

sterilization in the pre-packed

condition, deep penetration of the

gamma radiation and a single

parameter that controls the process i.e.

time of irradiation. Radiation

processing facilities provide a safe,

continuous and efficient method for

sterilization of healthcare products.

Radiation sterilization is an accepted

method for sterilization of a wide

variety of healthcare products more so

in the growing field of disposable

medical products. It is particularly

suitable for a large number of

products that may be either heat

sensitive or where use of ethylene

oxide is prohibited, for the presence

of toxic residual substances and

occupational hazard.

Moreover, being a continuous

process it is applicable to sterilization

of the products on a large scale.

Several developed and developing

countries have adopted gamma

radiation for sterilization of their

healthcare and medical products.

Gamma radiation processing facilities

worldwide mainly use sealed cobalt-

60 sources, which can be easily

2

produced in nuclear reactors, Cs-137

can also be used for this purpose.

International Organization for

Standardization (ISO) and American

Society for Testing and Materials

(ASTM) are the major organizations

that provide international standards on

a wide variety of applications of

science and technology. The

availability of standards on radiation

sterilization and related aspects from

these organizations has greatly

influenced and promoted the global

acceptance of the sterilization of

healthcare products using ionizing

radiation. This has substantially

improved the standard and availability

of quality sterilized healthcare

products. The impact of these

standards for the advancement of the

radiation sterilization technology can

not be underestimated.

ISO 11137 is considered as the

primary document for validation and

quality control of the process of

radiation sterilization. Technical

reports and specifications which apply

in particular or specific conditions and

are to be used in conjunction with this

standard are also available.

A radiation dose of 25 kGy for

sterilization of healthcare products is

universally accepted as effective in

rendering the products sterile with a

high degree of sterility assurance

level. This dose was used in the very

first applications of ionizing radiation

by Ethicon for sterilization of surgical

sutures.

The 25 kGy dose is considered

to have a high safety factor and is

believed to be suitable for most of the

materials used in the manufacture of

healthcare products. The accurate and

precise measurement of absorbed

dose is crucial in all radiation

processing applications and

sterilization is no exception.

ISO/ASTM standards on dosimetry

are also described.

For any given sterilization

method, microbiological evaluation of

the products before and after the

sterilization is naturally considered an

3

essential act. In fact, for some

traditional methods of sterilization

e.g. heat and ETO, the use of

biological indicators and/or sterility

tests are also to be performed for the

validation.

Microbiological aspects, not

necessarily restricted to radiation

sterilization, are subject of some

international standards. These

standards have also been included for

completeness.

Radiation Sterilization Standard –

ISO 11137

ISO 11137 has served the

radiation processing facilities in

providing the guidelines for

sterilization of healthcare products

since the time of its inception in 1991

and has since been revised in 1995.

The efforts are being made for

harmonization of this standard with

EN 552 a compatible standard on

radiation sterilization of medical

devices from European Committee for

Standardization (CEN). The extensive

revision of these standards is planned

to accommodate and base them on the

recent general sterilization standard

ISO 14937.

ISO standard 11137 describes

the process and quality control

requirements in context of

sterilization using ionizing radiation.

The products sterilized according to

the procedures and guidelines

described in this standard, are likely

to consistently yield good results,

provided, the specified sterilization

dose is imparted to the products, and

they are manufactured using good

manufacturing practices.

The standard covers terms and

definitions, requirements for

validation and procedures for

qualification of the irradiation facility,

process and products. The

significance of certification, routine

process control, and documentation as

applied to the radiation sterilization

has been dealt explicitly. Four

informative annexure are included in

this standard to enhance support to

the radiation sterilization application.

4

Annexure A discusses the device and

packaging material qualification.

Annexure B deals with the dose

setting methods – two methods have

been described for determination of

sterilization dose. Dosimeters,

dosimetry and associated equipment

have been mentioned in the annexure

C, where as bibliography and

reference material is provided in the

last annexure. The important radiation

sterilization standards, guidelines,

technical reports and specifications

are presented in the table-1.

Table – 1 Radiation Sterilization Standards, Technical Reports and

Specifications

Standard Description/Title Year

ISO 11137 Sterilization of Healthcare Products- Requirements for

Validation and Routine Control - Radiation

Sterilization

1991,

1995

ISO/TR

13409

Sterilization of Healthcare Products - Substantiation of

25 kGy for Radiation Sterilization of Small or

Infrequent Production Batches

1996

ISO/TR

15844

Sterilization of health care products- Radiation

Sterilization - Selection of Sterilization dose for a

single production batch

1998

ISO/TS

15843

Sterilization of Healthcare Products- Radiation

Sterilization- Product Families and Sampling Plans for

Verification Dose Experiments and Sterilization Dose

Audits, and Frequency of Sterilization Dose Audits

2000

EN 552 Validation and routine control of sterilization by

irradiation

(1994)

ANSI/AAMI

ST- 32

Guidelines for gamma radiation sterilization 1991

5

Technical Reports and Specification

used in conjunction with ISO 11137

A technical report ISO/TR

13409 addresses the substantiation of

the dose of 25 kGy for sterilization of

small or infrequent production

batches. ISO/TS 15843 describes the

issues related to product families,

sampling plans and dose verification

experiments for sterilization dose

audits and frequencies of such audits.

ISO/TR 15844 provides the methods

for selection of sterilization dose for a

single production batch.

Dosimetry – The General

Standards

Dosimetry is the science of the

measurement of absorbed dose when

matter is exposed to ionizing

radiation. The absorbed dose, defined

as the amount of energy imparted per

unit mass of the product on exposure

to ionizing radiation, is measured in

gray (Gy), 1 Gy is equivalent to 1

Joule/Kg. Often the accurate

measurement of the absorbed dose is

the only quality control parameter

employed for certifying the products

to be sterile, when using radiation

sterilization methods. Three

standards on the general aspects of

dosimetry are available jointly from

ISO and ASTM.

The standard ISO/ASTM

51261 describes the general criteria

for selection of a dosimetry system

and the calibration aspects.

ISO/ASTM 51400 describes the

characterization and performance

requirements of such a laboratory.

The standard ISO/ASTM 51707

addresses the concept of uncertainties

and their applications to radiation

dosimetry, this last standard assumes

further significance since the dose

from different laboratories is found to

be quite different due to uncertainties

introduced during measurement.

Table-2 lists these and

standards on terminology related

radiation measurement and dosimetry

and Practice for calculation of

6

absorbed dose from gamma or X-rays. .

Table-2 Standards on Guidelines and Practice of Dosimetry

Standard Description/Title Year

ASTM E170 Terminology relating to radiation measurement

and dosimetry

1999

ASTM E 666 Standard practice for calculating absorbed dose

from gamma or X-radiation

1997

ISO/ASTM

51261

Guide for Selection and Calibration of Dosimetry

Systems for Radiation Processing

2002

ISO/ASTM

51400

Practice for Characterization and Performance of a

High Dose Gamma Radiation Dosimetry

Calibration Laboratory

2002

ISO/ASTM

51707

Guide for Estimating Uncertainties in Dosimetry

for Radiation Processing

2002

Specific Dosimetry Systems

The measurement of absorbed

dose is carried out using a specific

dosimetry system. Some of the

dosimetry systems that can be used

for radiation sterilization, i.e. suitable

for the measurement of absorbed dose

of 25 kGy are listed Table-3.

The chemical or physical

changes imparted in the dosimeters

have well defined radiation yield that

can be correlated to the actual dose

absorbed in the products. Several

dosimetry systems have been

identified over the years and many of

them are suitable for the measurement

of absorbed dose during radiation

sterilization.

For example, Ceric-cerous

sulphate dosimeters (ISO/ASTM

51205) are widely employed in

radiation processing facilities to

7

calculate the absorbed dose. The

other systems which have received

much attention are alanine-EPR,

dichromate, ethanol-chlorobenzene,

radiochromic film and liquid

solutions, cellulose acetate, and

polymethylmethacrylate systems. The

selection of a particular dosimetry

system is governed by the availability

of the particular dosimeter system,

cost, availability of the necessary

apparatus/equipment.

Table-3 Standards related to Specific Dosimetry Systems

Standard Description/Title Year *

ISO/ASTM

51205

Practice for Use of a Ceric-Cerous Sulfate

Dosimetry System

2002

ISO/ASTM

51275

Practice for Use of a Radiochromic Film

Dosimetry System

2002

ISO/ASTM

51276

Practice for Use of a Polymethylmethacrylate

Dosimetry System

2002

ISO/ASTM

51401

Practice for Use of a Dichromate Dosimetry

System

2002

ISO/ASTM

51538

Practice for Use of an Ethanol-Chlorobenzene

Dosimetry System

2002

ISO/ASTM

51540

Practice for Use of a Radiochromic Liquid

Solution Dosimetry System

2002

ISO/ASTM

51607

Standard Practice for Use of the Alanine -EPR

Dosimetry System

2002

ISO/ASTM

51650

Practice for Use of a Cellulose Acetate Dosimetry

System

2002

* Existed earlier but jointly issued by ISO/ASTM in 2002

8

Dosimetry systems which can be

transported from one place to another

without having any effect on the

amount of absorbed dose over a

period of time are known as transfer

dosimetry systems. These are

particularly useful for national or

international validation of the

dosimetry systems. The absorbed

dose calculated using a specific

dosimetry system is compared with

the value obtained using transfer

dosimetry systems. Alanine-EPR

dosimetry system (ISO/ASTM 51607)

is used by IAEA and several other

which undertake the international

dose assurance services.

Microbiology Related Standards

Various microbiological

methods are required for

determination of the verification and

validation of sterilization dose as

mentioned in ISO 11137. The two

part ISO standard ISO 11737 is

particularly useful in this regard. The

first part of this standard can be used

for determination of bioburden on the

products. Whereas, second part is

particularly useful for conducting

sterility tests for validation of the

sterilization process. These standards

include informative annexures which

outline the various requirements for

materials, equipments, sampling

techniques, experimental methods and

presentation of results for the

microbiological evaluations.

Though use of Biological

indicators is not mandatory for use as

a quality control method in radiation

sterilization, BIs based on Bacillus

pumilus are in use for this purpose for

radiation sterilization. They provide

supplementary information and are

considered an actual proof of

microbial inactivation. Part I of ISO

11138 describes the general

requirements for the use of biological

indicators used in context of

sterilization of healthcare products.

Microbiology related standards are

grouped in Table 4.

9

Table-4 Microbiological Standards

Standard Description/Title Year

ISO 11737-1 Sterilization of Medical Devices- Microbiological

Methods - part 1: Estimation of population of

microorganisms on products

1995

ISO 11737-2 Sterilization of Medical Devices - Microbiological

Methods- Part 2: Tests of Sterility Performed in the

Validation of a Sterilization Process

1998

ISO 11138-1 Sterilization of Health Care Products - Biological

Indicators - Part 1: General

1994

ISO 14937 Sterilization of health care products - General

requirements for characterization of a sterilizing agent

and the development, validation and routine control of

a sterilization process for medical devices

2000

ISO 14937, which is a general

standard issued for sterilization of

health care products, describes the

requirements for characterization of

sterilizing agent and the development,

validation and routine control of a

sterilization process for medical

devices. It is expected that the

standards on sterilization using

radiation, ETO and moist steam are

also going to be developed on these

lines. The standard may well become

the major standard encompassing all

sterilization technologies.

There are specific standards for

quality control of medical devices

which are listed in ISO 14937 and

may be found useful in meeting the

requirements for medical devices.

References

1. Lambert, B.J. and Hansen,

J.M. (1998) ISO Radiation

10

Sterilization Standards.

Radiation Physics and

Chemistry Vol. 52(1-6) 11-14.

2. Morrissey, R.F. and Herring,

C.M. (2002) Radiation

sterilization: Past, Present and

Future. Radiation Physics and

Chemistry Vol. 63(3-6) 217-

221.

3. Miller, A. and Hansen, J.

(2002) Revision of the ISO

and EN Radiation Sterilization

Standards. Radiation Physics

and Chemistry Vol. 63(3-6)

665-667.

4. Note: Some of the major

organizations that have been

involved with the preparation

of standards, guidelines,

technical reports and

specifications pertaining to

radiation sterilizations and

various related aspects.

a. ISO – International

Organization for

Standardization - Case

Postale 56, CH-1211,

Geneve 20 Switzerland.

(website: www.iso.org)

b. ASTM – American

Society for Testing and

Materials – 100 Barr

Harbor Drive, West

Conshohocken, PA

19428 USA.

c. CEN – European

Committee for

Standardization – Rue de

Strassart 36, B-1050

Bruxelles, Belgium.

d. AAMI – Association for

the Advancement of

Medical Instruments,

1110 N Glebe Road,

Suite 220, Arlington, VA

22201-4795 USA.

e. ICRU – International

Commission on

Radiation Units and

Measurements, 7910

Woodmount Ave. Suite

800, Bethesda, MD

20814 USA.

ResearchGate has not been able to resolve any citations for this publication.

  • A. Miller A. Miller
  • Joyce Hansen

The radiation sterilization standards, ISO 11137 and EN 552, are now being revised under "ISO lead", with the aim of producing only one international standard, although in four parts: (1) requirements, (2) dose-setting methods, (3) dose-substantiation methods and (4) dosimetry. Several aspects of the old standards that have caused problems, when they were used in practice, are addressed in the revision. Input from users of the standards is necessary in order that the standards be developed as useful tools in the documentation of radiation sterilization.

  • Byron J. Lambert
  • Joyce M. Hansen

This presentation provides an overview of the current status of the ISO radiation sterilization standards. The ISO standards are voluntary standards which detail both the validation and routine control of the sterilization process. ISO 11137 was approved in 1994 and published in 1995. When reviewing the standard you will note that less than 20% of the standard is devoted to requirements and the remainder is guidance on how to comply with the requirements.Future standards developments in radiation sterilization are being focused on providing additional guidance. The guidance that is currently provided in informative annexes of ISO 11137 includes: device/packaging materials, dose setting methods, and dosimeters and dose measurement, currently, there are four Technical Reports being developed to provide additional guidance: 1.1. AAMI Draft TIR, "Radiation Sterilization Material Qualification"2.2. ISO TR 13409-1996, "Sterilization of health care products — Radiation sterilization — Substantiation of 25 kGy as a sterilization dose for small or infrequent production batches"3.3. ISO Draft TR, "Sterilization of health care products — Radiation sterilization Selection of a sterilization dose for a single production batch" li]4. ISO Draft TR, "Sterilization of health care products — Radiation sterilization-Product Families, Plans for Sampling and Frequency of Dose Audits."