Sterilization of medical devices – Requirements for medical devices to be designated “STERILE” – Part 1: Requirements for terminally sterilized medical devices

DIN EN 556-1:2002-03 (D)
Sterilisation von Medizinprodukten – Anforderungen an Medizinprodukte, die als
“STERIL” gekennzeichnet werden – Teil 1: Anforderungen an Medizinprodukte, die in
der Endpackung sterilisiert wurden; Deutsche Fassung EN 556-1:2001
Inhalt Seite
Vorwort ………………………………………………………………………………………………………………………………………..3
Einleitung ………………………………………………………………………………………………………………………………………4
1 Anwendungsbereich ……………………………………………………………………………………………………….4
2 Normative Verweisungen ………………………………………………………………………………………………..4
3 Begriffe …………………………………………………………………………………………………………………………..5
4 Anforderungen ……………………………………………………………………………………………………………….5
Anhang ZA (informativ) Abschnitte in dieser Europäischen Norm, die grundlegende
Anforderungen oder andere Vorgaben von EU-Richtlinien betreffen ………………………………..7
Literaturhinweise ……………………………………………………………………………………………………………………………8

EN 556-2 :2003: Sterilization of medical devices – Requirements for medical devices to be designated “STERILE” – Part 2: Requirements for aseptically processed medical devices

Einführungsbeitrag:

Medizinprodukte, die als “STERIL” gekennzeichnet werden, sind unter Verwendung geeigneter und validierter Verfahren herzustellen. Hierbei ist eine Sterilisation dieser Medizinprodukte in ihrer Endpackung nicht immer möglich. In diesem Fall bietet sich die aseptische Herstellung als alternatives Verfahren an.
In der Norm werden die Anforderungen festgelegt, die ein aseptisch hergestelltes Medizinprodukt erfüllen muss, wenn es als “STERIL” gekennzeichnet werden soll. Festgelegt wurden Anforderungen an den aseptischen Herstellungsprozess und an die Bereitstellung der Dokumentationen und Aufzeichnungen, die für den Nachweis der Übereinstimmung mit den Anforderungen benötigt werden.
Anforderungen an Medizinprodukte, die als “STERIL” gekennzeichnet werden sollen, jedoch durch Sterilisation in ihrer Endpackung hergestellt wurden, sind in DIN EN 556-1 angegeben.
Die Gegenüberstellung von Abschnitten der Norm und den grundlegenden Anforderungen der EG-Richtlinien 93/42/EWG über Medizinprodukte, 90/385/EWG über aktive implantierbare medizinische Geräte und 98/79/EG über In-vitro-Diagnostika ist in einem informativen Anhang enthalten.

DIN EN 556-2:2004-03 (D)
Sterilisation von Medizinprodukten – Anforderungen an Medizinprodukte, die als
“STERIL” gekennzeichnet werden – Teil 2: Anforderungen an aseptisch hergestellte
Medizinprodukte; Deutsche Fassung EN 556-2:2003
Inhalt Seite
Vorwort ………………………………………………………………………………………………………………………………………..3
Einleitung ………………………………………………………………………………………………………………………………………4
1 Anwendungsbereich ……………………………………………………………………………………………………….4
2 Normative Verweisungen ………………………………………………………………………………………………..4
3 Begriffe …………………………………………………………………………………………………………………………..5
4 Anforderungen ……………………………………………………………………………………………………………….6
4.1 Allgemeine Anforderungen ……………………………………………………………………………………………..6
4.2 Übereinstimmung, Validierung und Routineüberwachung ……………………………………………….6
4.3 Dokumentationen und Aufzeichnungen …………………………………………………………………………..6
Anhang ZA (informativ) Abschnitte in dieser Europäischen Norm, die grundlegende
Anforderungen oder andere Vorgaben von EU-Richtlinien betreffen ………………………………..7
Literaturhinweise ……………………………………………………………………………………………………………………………8

Sterilization of health care products – Radiation – Part 2: Establishing the sterilization dose (ISO 11137-2:2012)

Abstract

ISO 11137-2:2013 specifies methods for determining the minimum dose needed to achieve a specified requirement for sterility and methods to substantiate the use of 25 kGy or 15 kGy as the sterilization dose to achieve a sterility assurance level, SAL, of 10⁻⁶. ISO 11137-2:2013 also specifies methods of sterilization dose audit used to demonstrate the continued effectiveness of the sterilization dose.

ISO 11137-2:2013 defines product families for sterilization dose establishment and sterilization dose audit.

DIN EN ISO 11137-2:2013-09 (E)
Sterilization of health care products – Radiation – Part 2: Establishing the sterilization
dose (ISO 11137-2:2013)
Contents Page
Foreword ………………………………………………………………………………………………………………………………………. 4
Introduction …………………………………………………………………………………………………………………………………… 5
1 Scope …………………………………………………………………………………………………………………………….. 6
2 Normative references …………………………………………………………………………………………………….. 6
3 Terms, definitions, and abbreviated terms ………………………………………………………………………. 6
3.1 Terms and definitions …………………………………………………………………………………………………….. 6
3.2 Abbreviated terms ………………………………………………………………………………………………………….. 8
4 Definition and maintenance of product families for dose setting, dose substantiation,
and sterilization dose auditing ……………………………………………………………………………………….. 9
4.1 General ………………………………………………………………………………………………………………………….. 9
4.2 Defining product families ……………………………………………………………………………………………….. 9
4.3 Designation of product to represent a product family for performance of a verification
dose experiment or sterilization dose audit …………………………………………………………………… 10
4.4 Maintaining product families ………………………………………………………………………………………… 11
4.5 Effect of failure of establishment of sterilization dose or of a sterilization dose audit on a
product family ………………………………………………………………………………………………………………. 12
5 Selection and testing of product for establishing the sterilization dose …………………………. 12
5.1 Nature of product …………………………………………………………………………………………………………. 12
5.2 Sample item portion (SIP) …………………………………………………………………………………………….. 12
5.3 Manner of sampling ……………………………………………………………………………………………………… 14
5.4 Microbiological testing …………………………………………………………………………………………………. 14
5.5 Irradiation …………………………………………………………………………………………………………………….. 14
6 Methods of dose establishment ……………………………………………………………………………………. 14
7 Method 1: dose setting using bioburden information …………………………………………………….. 15
7.1 Rationale ……………………………………………………………………………………………………………………… 15
7.2 Procedure for Method 1 for product with an average bioburden greater than or equal to
1,0 for multiple production batches ………………………………………………………………………………. 16
7.3 Procedure for Method 1 for product with an average bioburden greater than or equal to
1,0 for a single production batch …………………………………………………………………………………… 22
7.4 Procedure for Method 1 for product with an average bioburden in the range 0,1 to 0,9 for
multiple or single production batches …………………………………………………………………………… 24
8 Method 2: Dose setting using fraction positive information from incremental dosing to
determine an extrapolation factor …………………………………………………………………………………. 25
8.1 Rationale ……………………………………………………………………………………………………………………… 25
8.2 Procedure for Method 2A ……………………………………………………………………………………………… 26
8.3 Procedure for Method 2B ……………………………………………………………………………………………… 29
9 Method VDmax — Substantiation of 25 kGy or 15 kGy as the sterilization dose ………………. 33
9.1 Rationale ……………………………………………………………………………………………………………………… 33
9.2 Procedure for Method VDmax 25 for multiple production batches …………………………………. 34
9.3 Procedure for Method VDmax 25 for a single production batch ……………………………………… 39
9.4 Procedure for Method VDmax 15 for multiple production batches …………………………………. 42

9.5 Procedure for Method VDmax 15 for a single production batch …………………………………….. 45
10 Sterilization dose audit ………………………………………………………………………………………………… 48
10.1 Purpose and frequency ………………………………………………………………………………………………… 48
10.2 Procedure for auditing a sterilization dose established using Method 1, Method 2A, or
Method 2B …………………………………………………………………………………………………………………… 48
10.3 Procedure for auditing a sterilization dose substantiated using Method VD max 25 or
Method VD max 15 ……………………………………………………………………………………………………….. 51
10.4 Failure of a sterilization dose audit ………………………………………………………………………………. 57
11 Worked examples ………………………………………………………………………………………………………… 57
11.1 Worked examples for Method 1 ……………………………………………………………………………………. 57
11.2 Worked examples for Method 2 ……………………………………………………………………………………. 59
11.3 Worked examples for Method Vdmax …………………………………………………………………………… 67
11.4 Worked example of a sterilization dose audit for a dose established using Method 1, the
findings from which necessitated augmentation of the sterilization dose ……………………… 69
11.5 Worked example of a sterilization dose audit for a dose established using Method 2A,
the findings from which necessitated augmentation of the sterilization dose ………………… 69
11.6 Worked example of a sterilization dose audit for a sterilization dose substantiated using
Method VDmax 25 ………………………………………………………………………………………………………… 70
Bibliography ……………………………………………………………………………………………………………………………….. 72
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on active implantable medical devices …………. 74
Annex ZB (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on medical devices ……………………………………….. 75
Annex ZC (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 98/79/EC on in vitro diagnostic medical devices …………….. 76

Sterilization of medical devices – Microbiological methods – Part 2: Tests of sterility performed in the definition, validation and maintenance of a sterilization process (ISO 11737-2:2009)

Abstract

ISO 11737-2:2009 specifies the general criteria for tests of sterility on medical devices that have been exposed to a treatment with the sterilizing agent reduced relative to that anticipated to be used in routine sterilization processing. These tests are intended to be performed when defining, validating or maintaining a sterilization process.

DIN EN ISO 11737-2:2010-04 (E)
Sterilization of medical devices – Microbiological methods – Part 2: Tests of sterility
performed in the definition, validation and maintenance of a sterilization process
(ISO 11737-2:2009)
Contents Page
Foreword ……………………………………………………………………………………………………………………………………….3
Introduction ……………………………………………………………………………………………………………………………………4
1 Scope ……………………………………………………………………………………………………………………………..5
2 Normative references ……………………………………………………………………………………………………..5
3 Terms and definitions ……………………………………………………………………………………………………..5
4 Quality management system elements …………………………………………………………………………….7
5 Selection of product ………………………………………………………………………………………………………..8
6 Methods for performing tests of sterility ………………………………………………………………………….9
7 Assessment of method for performing tests of sterility ………………………………………………….10
8 Maintenance of the method for performing tests of sterility ……………………………………………10
Annex A (informative) Guidance on tests of sterility performed in validation and maintenance of a
sterilization process ………………………………………………………………………………………………………11
Bibliography …………………………………………………………………………………………………………………………………19
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices ………….21
Annex ZB (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on Medical Devices …………………………………………22
Annex ZC (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 98/79/EC on in vitro diagnostic medical devices ………………23

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 (ISO 14937:2009)

Abstract

ISO 14937:2009 specifies general requirements for the characterization of a sterilizing agent and for the development, validation and routine monitoring and control of a sterilization process for medical devices.

It applies to sterilization processes in which microorganisms are inactivated by physical and/or chemical means and is intended to be applied by process developers, manufacturers of sterilization equipment, manufacturers of medical devices to be sterilized, and organizations responsible for sterilizing medical devices.

ISO 14937:2009 specifies the elements of a Quality Management System which are necessary to assure the appropriate characterization of the sterilizing agent, development, validation and routine monitoring and control of a sterilization process.

DIN EN ISO 14937:2010-03 (E)
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 (ISO 14937:2009)
Contents Page
Foreword ……………………………………………………………………………………………………………………………………….4
Introduction ……………………………………………………………………………………………………………………………………5
1 Scope ……………………………………………………………………………………………………………………………..7
1.1 Inclusions ……………………………………………………………………………………………………………………….7
1.2 Exclusions ……………………………………………………………………………………………………………………..7
2 Normative references ……………………………………………………………………………………………………..8
3 Terms and definitions ……………………………………………………………………………………………………..8
4 Quality management system elements …………………………………………………………………………..13
4.1 Documentation ……………………………………………………………………………………………………………..13
4.2 Management responsibility ……………………………………………………………………………………………13
4.3 Product realization ………………………………………………………………………………………………………..14
4.4 Measurement, analysis and improvement — Control of non-conforming product …………….14
5 Sterilizing agent characterization …………………………………………………………………………………..14
5.1 General …………………………………………………………………………………………………………………………14
5.2 Sterilizing agent …………………………………………………………………………………………………………….14
5.3 Microbicidal effectiveness …………………………………………………………………………………………….14
5.4 Effects on materials ………………………………………………………………………………………………………15
5.5 Safety and the environment …………………………………………………………………………………………..15
6 Process and equipment characterization ……………………………………………………………………….15
6.1 General …………………………………………………………………………………………………………………………15
6.2 Process characterization ……………………………………………………………………………………………….15
6.3 Equipment characterization …………………………………………………………………………………………..16
7 Product definition ………………………………………………………………………………………………………….16
8 Process definition …………………………………………………………………………………………………………17
9 Validation ……………………………………………………………………………………………………………………..18
9.1 General …………………………………………………………………………………………………………………………18
9.2 Installation qualification ………………………………………………………………………………………………..18
9.3 Operational qualification ……………………………………………………………………………………………….19
9.4 Performance qualification ……………………………………………………………………………………………..19
9.5 Review and approval of validation …………………………………………………………………………………20
10 Routine monitoring and control …………………………………………………………………………………….20
11 Product release from sterilization ………………………………………………………………………………….20
12 Maintaining process effectiveness …………………………………………………………………………………21
12.1 General …………………………………………………………………………………………………………………………21
12.2 Recalibration …………………………………………………………………………………………………………………21
12.3 Maintenance of equipment …………………………………………………………………………………………….21

12.4 Requalification …………………………………………………………………………………………………………….. 21
12.5 Assessment of change ………………………………………………………………………………………………… 21
Annex A (normative) Factors to be considered in selection of microorganisms for demonstrating
microbicidal effectiveness ……………………………………………………………………………………………. 22
Annex B (normative) Approach 1 — Process definition based on inactivation of the microbial
population in its natural state ………………………………………………………………………………………. 24
Annex C (normative) Approach 2 — Process definition based on inactivation of reference
microorganisms and knowledge of bioburden ……………………………………………………………… 25
Annex D (normative) Approach 3 — Conservative process definition based on inactivation of
reference microorganisms …………………………………………………………………………………………… 26
Annex E (informative) Guidance on application of this International Standard ……………………………… 28
Bibliography ……………………………………………………………………………………………………………………………….. 42
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices ………… 44
Annex ZB (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on Medical Devices ……………………………………….. 45
Annex ZC (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 98/79/EC on in vitro diagnostic medical devices …………….. 46