ANSI/AAMI/ISO 11140-1:2005 -- Sterilization of health care ... · All AAMI standards, recommended...

American National Standard

ANSI/AAMI/ISO 11140-1:2005

Sterilization of health care products— Chemical indicators—

Part 1: General requirements

The Objectives and Uses of AAMI Standards andRecommended Practices

It is most important that the objectives and potential uses of an AAMIproduct standard or recommended practice are clearly understood.The objectives of AAMI's technical development program derivefrom AAMI's overall mission: the advancement of medicalinstrumentation. Essential to such advancement are (1) a continuedincrease in the safe and effective application of current technologiesto patient care, and (2) the encouragement of new technologies. It isAAMI's view that standards and recommended practices cancontribute significantly to the advancement of medicalinstrumentation, provided that they are drafted with attention to theseobjectives and provided that arbitrary and restrictive uses are avoided.

A voluntary standard for a medical device recommends to themanufacturer the information that should be provided with or on theproduct, basic safety and performance criteria that should be con-sidered in qualifying the device for clinical use, and the measurementtechniques that can be used to determine whether the device conformswith the safety and performance criteria and/or to compare the per-formance characteristics of different products. Some standards em-phasize the information that should be provided with the device,including performance characteristics, instructions for use, warningsand precautions, and other data considered important in ensuring thesafe and effective use of the device in the clinical environment.Recommending the disclosure of performance characteristics oftennecessitates the development of specialized test methods to facilitateuniformity in reporting; reaching consensus on these tests canrepresent a considerable part of committee work. When a draftingcommittee determines that clinical concerns warrant the establishmentof minimum safety and performance criteria, referee tests must beprovided and the reasons for establishing the criteria must bedocumented in the rationale.

A recommended practice provides guidelines for the use, care,and/or processing of a medical device or system. A recommendedpractice does not address device performance per se, but ratherprocedures and practices that will help ensure that a device is usedsafely and effectively and that its performance will be maintained.

Although a device standard is primarily directed to the manufac-turer, it may also be of value to the potential purchaser or user of thedevice as a fume of reference for device evaluation. Similarly, eventhough a recommended practice is usually oriented towards healthcare professionals, it may be useful to the manufacturer in betterunderstanding the environment in which a medical device will beused. Also, some recommended practices, while not addressing deviceperformance criteria, provide guidelines to industrial personnel onsuch subjects as sterilization processing, methods of collecting data toestablish safety and efficacy, human engineering, and otherprocessing or evaluation techniques; such guidelines may be useful tohealth care professionals in understanding industrial practices.

In determining whether an AAMI standard or recommendedpractice is relevant to the specific needs of a potential user of thedocument, several important concepts must be recognized:

All AAMI standards and recommended practices are voluntary(unless, of course, they are adopted by government regulatory orprocurement authorities). The application of a standard or recom-mended practice is solely within the discretion and professionaljudgment of the user of the document.

Each AAMI standard or recommended practice reflects thecollective expertise of a committee of health care professionals andindustrial representatives, whose work has been reviewed nationally(and sometimes internationally). As such, the consensusrecommendations embodied in a standard or recommended practiceare intended to respond to clinical needs and, ultimately, to helpensure patient safety. A standard or recommended practice is limited,however, in the sense that it responds generally to perceived risks andconditions that may not always be relevant to specific situations. Astandard or recommended practice is an important reference inresponsible decision-making, but it should never replace responsibledecisionmaking.

Despite periodic review and revision (at least once every fiveyears), a standard or recommended practice is necessarily a staticdocument applied to a dynamic technology. Therefore, a standardsuser must carefully review the reasons why the document wasinitially developed and the specific rationale for each of itsprovisions. This review will reveal whether the document remainsrelevant to the specific needs of the user.

Particular care should be taken in applying a product standard toexisting devices and equipment, and in applying a recommendedpractice to current procedures and practices. While observed orpotential risks with existing equipment typically form the basis for thesafety and performance criteria defined in a standard, professionaljudgment must be used in applying these criteria to existing equip-ment. No single source of information will serve to identify aparticular product as "unsafe". A voluntary standard can be used asone resource, but the ultimate decision as to product safety andefficacy must take into account the specifics of its utilization and, ofcourse, cost-benefit considerations. Similarly, a recommendedpractice should be analyzed in the context of the specific needs andresources of the individual institution or firm. Again, the rationaleaccompanying each AAMI standard and recommended practice is anexcellent guide to the reasoning and data underlying its provision.

In summary, a standard or recommended practice is truly usefulonly when it is used in conjunction with other sources of informationand policy guidance and in the context of professional experience andjudgment.

INTERPRETATIONS OF AAMI STANDARDSAND RECOMMENDED PRACTICES

Requests for interpretations of AAMI standards and recommendedpractices must be made in writing, to the Manager for TechnicalDevelopment. An official interpretation must be approved by letterballot of the originating committee and subsequently reviewed andapproved by the AAMI Standards Board. The interpretation willbecome official and representation of the Association only uponexhaustion of any appeals and upon publication of notice of interpre-tation in the "Standards Monitor" section of the AAMI News. TheAssociation for the Advancement of Medical Instrumentationdisclaims responsibility for any characterization or explanation of astandard or recommended practice which has not been developed andcommunicated in accordance with this procedure and which is notpublished, by appropriate notice, as an official interpretation in theAAMI News.

American National Standard ANSI/AAMI/ISO 11140-1:2005 (Revision of ANSI/AAMI ST60:1996)

Sterilization of health care products— Chemical indicators—Part 1: General requirements

Developed by Association for the Advancement of Medical Instrumentation Approved 14 December 2005 by American National Standards Institute, Inc. Abstract: Specifies performance requirements for indicators that show exposure to sterilization processes

by means of physical and/or chemical change of substances.

Keywords: acceptance criteria, dry heat, ethylene oxide, performance requirements, radiation, steam

AAMI Standard

This Association for the Advancement of Medical Instrumentation (AAMI) standard implies a consensus of those substantially concerned with its scope and provisions. The existence of an AAMI standard does not in any respect preclude anyone, whether they have approved the standard or not, from manufacturing, marketing, purchasing, or using products, processes, or procedures not conforming to the standard. AAMI standards are subject to periodic review, and users are cautioned to obtain the latest editions.

CAUTION NOTICE: This AAMI standard may be revised or withdrawn at any time. AAMI procedures require that action be taken to reaffirm, revise, or withdraw this standard no later than five years from the date of publication. Interested parties may obtain current information on all AAMI standards by calling or writing AAMI.

All AAMI standards, recommended practices, technical information reports, and other types of technical documents developed by AAMI are voluntary, and their application is solely within the discretion and professional judgment of the user of the document. Occasionally, voluntary technical documents are adopted by government regulatory agencies or procurement authorities, in which case the adopting agency is responsible for enforcement of its rules and regulations.

Published by Association for the Advancement of Medical Instrumentation 1110 N. Glebe Road, Suite 220 Arlington, VA 22201-4795 © 2006 by the Association for the Advancement of Medical Instrumentation All Rights Reserved This publication is subject to copyright claims of ISO, ANSI, and AAMI. No part of this publication may be reproduced or distributed in any form, including an electronic retrieval system, without the prior written permission of AAMI. All requests pertaining to this document should be submitted to AAMI. It is illegal under federal law (17 U.S.C. § 101, et seq.) to make copies of all or any part of this document (whether internally or externally) without the prior written permission of the Association for the Advancement of Medical Instrumentation. Violators risk legal action, including civil and criminal penalties, and damages of $100,000 per offense. For permission regarding the use of all or any part of this document, contact AAMI, 1110 N. Glebe Road, Suite 220, Arlington, VA 22201-4795. Phone: (703) 525-4890; Fax: (703) 525-1067. Printed in the United States of America ISBN 1–57020–242–7

Contents

Page

Glossary of equivalent standards .....................................................................................................................v Committee representation .............................................................................................................................. vii Background of AAMI adoption of ISO 11140-1:2005 ...................................................................................... ix Foreword ..........................................................................................................................................................x Introduction ..................................................................................................................................................... xi 1 Scope........................................................................................................................................................1 2 Normative references................................................................................................................................1 3 Terms and definitions................................................................................................................................1 4 Classification.............................................................................................................................................2

4.1 General ..........................................................................................................................................2 4.2 Class 1: Process indicators ............................................................................................................2 4.3 Class 2: Indicators for use in specific tests.....................................................................................2 4.4 Class 3: Single variable indicators .................................................................................................2 4.5 Class 4: Multi-variable indicators....................................................................................................2 4.6 Class 5: Integrating indicators ........................................................................................................2 4.7 Class 6: Emulating indicators .........................................................................................................3

5 General requirements ...............................................................................................................................3 6 Performance requirements........................................................................................................................4

6.1 General ..........................................................................................................................................4 6.2 Class 1 indicators...........................................................................................................................4 6.3 Class 2 indicators...........................................................................................................................5 6.4 Classes 3, 4, 5, and 6 indicators ....................................................................................................5

7 Test methods ............................................................................................................................................5 7.1 General ..........................................................................................................................................5 7.2 Off-set (transference) .....................................................................................................................5 7.3 Procedure—Steam indicators ........................................................................................................5 7.4 Procedure—Dry heat indicators .....................................................................................................5 7.5 Procedure—EO indicators..............................................................................................................6 7.6 Procedure—Steam-formaldehyde indicators..................................................................................6 7.7 Procedure—Vaporized hydrogen peroxide indicators ....................................................................7

8 Additional requirements for process (Class 1) indicators ..........................................................................7 8.1 Process indicators printed or applied onto packaging material.......................................................7 8.2 Process indicators for steam sterilization processes......................................................................7 8.3 Process indicators for dry heat sterilization processes...................................................................8 8.4 Process indicators for ethylene oxide sterilization processes.........................................................8 8.5 Process indicators for irradiation sterilization processes ................................................................9 8.6 Process indicators for steam-formaldehyde sterilization processes ...............................................9 8.7 Process indicators for vaporized hydrogen peroxide sterilization processes................................10

9 Additional requirements for single variable (Class 3) indicators ..............................................................10 10 Additional requirements for multi-variable (Class 4) indicators................................................................10 11 Additional requirements for steam integrating (Class 5) indicators .........................................................11

12 Additional requirements for dry heat integrating (Class 5) indicators ......................................................12 13 Additional requirements for ethylene oxide integrating (Class 5) indicators ............................................12 14 Additional requirements for emulating (Class 6) indicators .....................................................................13 Annexes

A Method for demonstrating shelf life of the product ..................................................................................14 B Examples of testing indicators ................................................................................................................15 C Rationale for the requirements for integrating indicators and the link to the requirements

for biological indicators (BIs) specified in ISO 11138 and microbial inactivation .....................................16 D Rationale for the liquid-phase test method for steam-formaldehyde indicators .......................................22 E Relationship of indicator components .....................................................................................................23 Bibliography ...................................................................................................................................................24

Tables

1 Test and performance requirements for Class 1 process indicators for STEAM.......................................7 2 Test and performance requirements for Class 1 process indicators for DRY............................................8 3 Test and performance requirements for Class 1 process indicators for EO ..............................................8 4 Test and performance requirements for Class 1 process indicators for IRRAD ........................................9 5 Test conditions and performance requirements for Class 1 process indicators for FORM........................9 6 Test conditions and performance requirements for Class 1 process indicators for VH2O2 ....................10 7 Test and performance requirements for Class 3 and Class 4 indicators .................................................11 8 Test and performance requirements for Class 6 indicators.....................................................................13 C.1 BI survivor level.......................................................................................................................................19

© 2006 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 11140-1:2005 v

Glossary of equivalent standards

International Standards adopted in the United States may include normative references to other International Standards. For each International Standard that has been adopted by AAMI (and ANSI), the table below gives the corresponding U.S. designation and level of equivalency to the International Standard.

NOTE—Documents are sorted by international designation.

Other normatively referenced International Standards may be under consideration for U.S. adoption by AAMI; therefore, this list should not be considered exhaustive.

International designation U.S. designation Equivalency IEC 60601-1:2005 ANSI/AAMI ES60601-1:2005 Major technical variations IEC 60601-1-2:2001 and Amendment 1:2004

ANSI/AAMI/IEC 60601-1-2:2001 and Amendment 1:2004

Identical

IEC 60601-2-04:2002 ANSI/AAMI DF80:2003 Major technical variations IEC 60601-2-19:1990 and Amendment 1:1996

ANSI/AAMI II36:2004 Major technical variations

IEC 60601-2-20:1990 and Amendment 1:1996

ANSI/AAMI II51:2004 Major technical variations

IEC 60601-2-21:1994 and Amendment 1:1996

ANSI/AAMI/IEC 60601-2-21 and Amendment 1:2000 (consolidated texts)

Identical

IEC 60601-2-24:1998 ANSI/AAMI ID26:2004 Major technical variations IEC TR 60878:2003 ANSI/AAMI/IEC TIR60878:2003 Identical IEC TR 62296:2003 ANSI/AAMI/IEC TIR62296:2003 Identical IEC TR 62348:200x1 ANSI/AAMI/IEC TIR62348:2006 Identical ISO 5840:2005 ANSI/AAMI/ISO 5840:2005 Identical ISO 7198:1998 ANSI/AAMI/ISO 7198:1998/2001/(R)2004 Identical ISO 7199:1996 ANSI/AAMI/ISO 7199:1996/(R)2002 Identical ISO 10993-1:2003 ANSI/AAMI/ISO 10993-1:2003 Identical ISO 10993-2:1992 ANSI/AAMI/ISO 10993-2:1993/(R)2001 Identical ISO 10993-3:2003 ANSI/AAMI/ISO 10993-3:2003 Identical ISO 10993-4:2002 ANSI/AAMI/ISO 10993-4:2002 Identical ISO 10993-5:1999 ANSI/AAMI/ISO 10993-5:1999 Identical ISO 10993-6:1994 ANSI/AAMI/ISO 10993-6:1995/(R)2001 Identical ISO 10993-7:1995 ANSI/AAMI/ISO 10993-7:1995/(R)2001 Identical ISO 10993-9:1999 ANSI/AAMI/ISO 10993-9:1999/(R)2005 Identical ISO 10993-10:2002 ANSI/AAMI BE78:2002 Minor technical variations ISO 10993-11:1993 ANSI/AAMI 10993-11:1993 Minor technical variations ISO 10993-12:2002 ANSI/AAMI/ISO 10993-12:2002 Identical ISO 10993-13:1998 ANSI/AAMI/ISO 10993-13:1999/(R)2004 Identical ISO 10993-14:2001 ANSI/AAMI/ISO 10993-14:2001 Identical ISO 10993-15:2000 ANSI/AAMI/ISO 10993-15:2000 Identical ISO 10993-16:1997 ANSI/AAMI/ISO 10993-16:1997/(R)2003 Identical ISO 10993-17:2002 ANSI/AAMI/ISO 10993-17:2002 Identical ISO TS 10993-19:200x1 ANSI/AAMI/ISO TIR10993-19:2006 Identical ISO TS 10993-20:200x1 ANSI/AAMI/ISO TIR10993-20:2006 Identical ISO 11135:1994 ANSI/AAMI/ISO 11135:1994 Identical

vi © 2006 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 11140-1:2005

International designation U.S. designation Equivalency ISO 11137-1:200x1 ANSI/AAMI/ISO 11137-1:2006 Identical ISO 11137-2:200x1 ANSI/AAMI/ISO 11137-2:2006 Identical ISO 11137-3:200x1 ANSI/AAMI/ISO 11137-3:2006 Identical ISO 11138-1: 200x1 ANSI/AAMI/ISO 11138-1:2006 Identical ISO 11138-2: 200x1 ANSI/AAMI/ISO 11138-2:2006 Identical ISO 11138-3:1995 ANSI/AAMI ST19:1999 Major technical variations ISO 11138-4: 200x1 ANSI/AAMI/ISO 11138-4:2006 Identical ISO 11138-5: 200x1 ANSI/AAMI/ISO 11138-5:2006 Identical ISO TS 11139:2006 ANSI/AAMI/ISO 11139:2006 Identical ISO 11140-1:2005 ANSI/AAMI/ISO 11140-1:2005 Identical ISO 11140-5:2000 ANSI/AAMI ST66:1999 Major technical variations ISO 11607-1:200x1 ANSI/AAMI/ISO 11607-1:2006 Identical ISO 11607-2:200x1 ANSI/AAMI/ISO 11607-2:2006 Identical ISO 11737-1: 200x1 ANSI/AAMI/ISO 11737-1:2006 Identical ISO 11737-2:1998 ANSI/AAMI/ISO 11737-2:1998 Identical ISO 11737-3:2004 ANSI/AAMI/ISO 11737-3:2004 Identical ISO 13485:2003 ANSI/AAMI/ISO 13485:2003 Identical ISO 13488:1996 ANSI/AAMI/ISO 13488:1996 Identical ISO 14155-1:2003 ANSI/AAMI/ISO 14155-1:2003 Identical ISO 14155-2:2003 ANSI/AAMI/ISO 14155-2:2003 Identical ISO 14160:1998 ANSI/AAMI/ISO 14160:1998 Identical ISO 14161:2000 ANSI/AAMI/ISO 14161:2000 Identical ISO 14937:2000 ANSI/AAMI/ISO 14937:2000 Identical ISO TR 14969:2004 ANSI/AAMI/ISO TIR14969:2004 Identical ISO 14971:2000 and A1:2003 ANSI/AAMI/ISO 14971:2000 and A1:2003 Identical ISO 15223:2000, A1:2002, and A2:2004

ANSI/AAMI/ISO 15223:2000, A1:2001, and A2:2004

Identical

ISO 15225:2000 and A1:2004 ANSI/AAMI/ISO 15225:2000/(R)2006 and A1:2004/(R)2006

Identical

ISO 15674:2001 ANSI/AAMI/ISO 15674:2001 Identical ISO 15675:2001 ANSI/AAMI/ISO 15675:2001 Identical ISO TS 15843:2000 ANSI/AAMI/ISO TIR15843:2000 Identical ISO 15882:2003 ANSI/AAMI/ISO 15882:2003 Identical ISO TR 16142:2006 ANSI/AAMI/ISO TIR16142:2006 Identical ISO 17664:2004 ANSI/AAMI ST81:2004 Major technical variations ISO 17665-1:200x1 ANSI/AAMI/ISO 17665-1:2006 Identical ISO 18472:200x1 ANSI/AAMI/ISO 18472:2006 Identical ISO TS 19218:2005 ANSI/AAMI/ISO 19218:2005 Identical ISO 25539-1:2003 and A1:2005 ANSI/AAMI/ISO 25539-1:2003 and

A1:2005 Identical

© 2006 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 11140-1:2005 vii

Committee representation

Association for the Advancement of Medical Instrumentation

Chemical Indicators Working Group

The adoption of ISO 11140-1:2005 as an American National Standard was initiated by the AAMI Chemical Indicators Working Group of the AAMI Sterilization Standards Committee. The AAMI Chemical Indicators Working Group also functions as a U.S. Technical Advisory Group to the relevant work in the International Organization for Sterilization (ISO). U.S. representatives from the AAMI Chemical Indicators Working Group (U.S. Sub-TAG for ISO/TC 198/WG 6, Chemical indicators) played an active part in developing the ISO standard. At the time this document was published, the AAMI Chemical Indicators Working Group had the following members: Chair: Joel R. Gorski, PhD Members: Richard Bancroft, Albert Browne Ltd.

Heidi L. Betti, CST CRCST, Mercy Hospital Center for Health Carl W. Bruch, PhD, Biotest Laboratories Inc. Loran H. Bruso, BS, MBA, Steritec Products Manufacturing Company Inc. Marc Chaunet, TSO3 Inc. Anthony J. DeMarinis, BS, MS, CQA, CQM, Davol Inc. Joseph R. Durbin, Hospira Inc. Martin S. Favero, Johnson & Johnson Advanced Sterilization Products Gloria H. Frost, PhD, Cardinal Health Joel R. Gorski, PhD, NAMSA Steve Kirckof, 3M Healthcare Colleen Patricia Landers, RN, Central Service Association of Ontario Ted May, Anderson Products Inc. Patrick McCormick, PhD, Bausch & Lomb Inc. Bobby Osburn, Department of Veteran Affairs Wendy Royalty-Hann, Raven Biological Laboratories Jennifer L. Schmidt, Office of Device Evaluations/Center for Devices and Radiological Health/U.S.

Food and Drug Administration Andrew Sharavara, Propper Manufacturing Company Inc. Barbara Smith, Getinge USA Gary J. Socola, SPS Medical Supply Corporation Jonathan A. Wilder, PhD, H&W Technology LLC

Alternates: Thomas J. Berger, PhD, Hospira Inc. Kimbrell Darnell, Bard Medical Division Chris Dwyer, Raven Biological Laboratories Charles A. Hughes, SPS Medical Gretchen Keenan, 3M Healthcare John Lindley, Andersen Products Inc. Michael Mattison, Getinge USA Deborah McGrath, Bausch & Lomb Inc. Richard T. O’Donnell, Steris Corporation Joseph Palomo, Cardinal Health Mahesh Patel, Propper Manufacturing Company Inc. Shaundrea L. Rechsteiner, NAMSA Michelle Rios, Office of Device Evaluations/Center for Devices and Radiological Health/U.S. Food and

Drug Administration Su-Syin Wu, PhD, Johnson & Johnson Advanced Sterilization Products

NOTE—Participation by federal agency representatives in the development of this recommended practice does not constitute endorsement by the federal government or any of its agencies.

viii © 2006 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 11140-1:2005

AAMI Sterilization Standards Committee Cochairs: Victoria M. Hitchins, PhD

William E. Young Members: Trabue D. Bryans, AppTec

Virginia C. Chamberlain, PhD, VC Chamberlain & Associates (Independent Expert) Nancy Chobin, RN,CSPDM, St Barnabas Healthcare System (Independent Expert) Anne M. Cofiell, CRCST, FCS, IAHCSMM Charles Cogdill, Boston Scientific Corp. Ramona Conner, RN MSN CNOR, Association of Perioperative Registered Nurses Jacqueline Daley, Association for Professionals in Infection Control and Epidemiology Kimbrell Darnell, CR Bard Lisa Foster, Sterigenics International James M. Gibson Jr., JM Gibson Associates Barbara J. Goodman, RN, BS, CNOR, (Independent Expert) Joel R. Gorski, PhD, NAMSA Deborah A. Havlik, Hospira Inc. Victoria M. Hitchins, PhD, FDA/CDRH Richard M. Johnson, MSc,BSc, Abbott Laboratories Lois Atkinson Jones, MS (Independent Expert) Byron J. Lambert, PhD, Guidant Corporation/Cardiac Rhythm Management Colleen Patricia Landers, RN, Canadian Standards Association David Liu, Johnson & Johnson Jeff Martin, Alcon Laboratories Inc.

Patrick J. McCormick, PhD, Bausch & Lomb Inc. Thomas K. Moore, Getinge USA Barry F. J. Page, Barry Page Consulting (Independent Expert) Nancy J. Rakiewicz, Ethox Corp. Phil M. Schneider, 3M Healthcare Michael H. Scholla, Dupont Nonwovens Mark Seybold, Baxter Healthcare Corp. Andrew Sharavara, Propper Manufacturing Co. Inc. Frank Sizemore, American Society for Healthcare Central Service Professionals Gregory O. Stecklein, MS MSM, Cardinal Health William N. Thompson, TYCO Healthcare/Kendall John W. Walker, Steris Corp. James L. Whitby, MA, MB, FRCP, University of Western Ontario (Independent Expert) Thelma Wilcott, Becton Dickinson & Company Martell Kress Winters, B.S., SM, Nelson Laboratories Inc. William E. Young (Independent Expert)

Alternates: Lloyd Brown, TYCO Healthcare/Kendall Lina C. Bueno, Dupont Nonwovens Craig M. Herring, Johnson & Johnson Clark W. Houghtling, Steris Corp. Danny Hutson, Cardinal Health Jim Kaiser, Bausch & Lomb Inc. Susan G. Klacik, AS BS, IAHCSMM Joseph J. Lasich, BS, Alcon Laboratories Inc. Chiu Lin, PhD, FDA/CDRH Lisa N. Macdonald, Becton Dickinson & Company Ralph Makinen, Guidant Corporation/Cardiac Rhythm Management Mary S. Mayo, CR Bard David Ford McGoldrick, BS, Abbott Laboratories Jerry R. Nelson, MS PhD, Nelson Laboratories Inc. Jeff Peltier, Boston Scientific Corp. Janet Prust, 3M Healthcare Mike Sadowski, Baxter Healthcare Corp. Ralph Stick, AppTec Jason Voisinet, Ethox Corp.

Valerie Welter, Hospira Inc. William T. Young, Sterigenics International

NOTE—Participation by federal agency representatives in the development of this standard does not constitute endorsement by the federal government or any of its agencies.

© 2006 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 11140-1:2005 ix

Background of AAMI adoption of ISO 11140-1:2005

As indicated in the foreword to the main body of this document (page x), the International Organization for Standardization (ISO) is a worldwide federation of national standards bodies. The United States is one of the ISO members that took an active role in the development of this standard, which was developed by ISO Technical Committee 198, Sterilization of health care products, to fill a need to specify requirements for chemical indicators intended for use with sterilization processes employing steam, ethylene oxide, γ- or β-radiation, steam-formaldehyde, vaporized hydrogen peroxide, or dry heat.

U.S. participation in this ISO TC is organized through the U.S. Technical Advisory Group for ISO/TC 198, administered by the Association for the Advancement of Medical Instrumentation (AAMI). The U.S. TAG for ISO/TC 198 supports the requirements provided in this document.

The U.S. adoption of ISO 11140-1:2005 was approved by the American National Standards Institute (ANSI) as a revision of ST60:1996, Sterilization of health care products—Chemical indicators—Part 1: General requirements on 14 December 2005. The AAMI Chemical Indicators Working Group (U.S. Sub-TAG for ISO/TC 198/WG 6, Chemical indicators) developed ST60:1996 and initiated the U.S. adoption of ISO 11140-1-2005.

The main differences between ANSI/AAMI/ISO 11140-1:2005 and ST60:1996 include the addition in 11140-1:2005 of Class 1 indicators, vaporized hydrogen peroxide indicators, a step-by-step sequence of events for exposure of chemical indicators in resistometers leading to better consistency in the characterization of chemical indicator products, refinement of the Class 5 Integrating Indicator performance specifications, Class 6 indicators, and overall updating and refinement of general requirements for chemical indicators in the new edition.

AAMI and ANSI procedures require that standards be reviewed and, if necessary, revised every five years to reflect technological advances that may have occurred since publication.

AAMI (and ANSI) have adopted other ISO standards. See the Glossary of Equivalent Standards for a list of ISO standards adopted by AAMI, which gives the corresponding U.S. designation and the level of equivalency with the ISO standard.

The concepts incorporated in this standard should not be considered inflexible or static. This standard, like any other, must be reviewed and updated periodically to assimilate progressive technological developments. To remain relevant, it must be modified as technological advances are made and as new data come to light.

Suggestions for improving this standard are invited. Comments and suggested revisions should be sent to Standards Department, AAMI, 1110 N. Glebe Road, Suite 220, Arlington, VA 22201-4795.

NOTE—Beginning with the foreword on page x, this American National Standard is identical to ISO 11140-1:2005.

x © 2006 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 11140-1:2005

Foreword

ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISO member bodies). The work of preparing International Standards is normally carried out through ISO technical committees. Each member body interested in a subject for which a technical committee has been established has the right to be represented on that committee. International organizations, governmental and non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.

International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.

The main task of technical committees is to prepare International Standards. Draft International Standards adopted by the technical committees are circulated to the member bodies for voting. Publication as an International Standard requires approval by at least 75 % of the member bodies casting a vote.

Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights.

ISO 11140-1 was prepared by Technical Committee ISO/TC 198, Sterilization of health care products.

This second edition cancels and replaces the first edition, (ISO 11140-1:1995 and ISO 11140-1:1005/Amd.1:1998, which has been technically revised.

ISO 11140 consists of the following parts, under the general title Sterilization of health care products—Chemical indicators:

— Part 1: General requirements

— Part 2: Test equipment and methods

— Part 3: Class 2 indicators for steam penetration test sheets

— Part 4: Class 2 indicators for steam penetration test packs

— Part 5: Class 2 indicators for air removal test sheets and packs

NOTE—ISO 11140-2 will be replaced by ISO 18472, Sterilization of health care products—Biological and chemical indicators— Test equipment.

© 2006 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 11140-1:2005 xi

Introduction

This part of ISO 11140 specifies performance requirements and/or test methods for chemical indicators intended for use with sterilization processes employing steam, dry heat, ethylene oxide, γ or β radiation, steam-formaldehyde, or vaporized hydrogen peroxide.

Additional requirements for indicators intended for use with other sterilization methods (e.g., other forms of moist heat sterilization) are not specifically provided in this part of ISO 11140; however, the general requirements will apply.

The requirements for specific test indicators (e.g., Bowie-Dick test indicators) are covered in other parts of ISO 11140.

Standards for sterilizers and for the validation and process control of sterilization describe performance tests for sterilizers and methods of validation and routine control, respectively.

This part of ISO 11140 is intended for manufacturers of chemical indicators and specifies the general requirements for chemical indicators. Subsequent parts of this International Standard specify the particular requirements for chemical indicators for particular applications and for defined tests of particular sterilization processes used in health care, including industry. The use of the indicators specified in this part of ISO 11140 are described in ISO 15882, EN 285, ISO 11135, and ISO 17665.

Resistometers (see ISO 18472) are used to characterize the performance of the chemical indicators described in this part of ISO 11140. Resistometers allow for precise variation of the specific test conditions and cycle sequences in order to produce controlled physical studies. Resistometers differ from conventional sterilizers; therefore, if conventional sterilizers are used to attempt to duplicate resistometer conditions, erroneous and/or misleading results may occur.

© 2005 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 11140-1:2005 1

American National Standard ANSI/AAMI/ISO 11140-1:2005

Sterilization of health care products— Chemical indicators—Part 1: General requirements WARNING—The use of this part of ISO 11140 may involve hazardous materials, operations, and equipment. This part of ISO 11140 does not purport to address all of the safety problems associated with its use. It is the responsibility of the user of this part of ISO 11140 to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to use.

1 Scope

1.1 This part of ISO 11140 specifies general requirements and test methods for indicators that show exposure to sterilization processes by means of physical and/or chemical change of substances, and which are used to monitor the attainment of one or more of the variables required for a sterilization process. They are not dependent for their action on the presence or absence of a living organism.

NOTE—Biological test systems are regarded as those tests which are dependent for their interpretation on the demonstration of the viability of an organism. Test systems of this type are considered in the ISO 11138 series for biological indicators (BIs).

1.2 The requirements and test methods of this part of ISO 11140 apply to all indicators specified in subsequent parts of ISO 11140, unless the requirement is modified or added to by a subsequent part, in which case the requirement of that particular part will apply.

Relevant test equipment is described in ISO 18472.

NOTE—Additional requirements for specific test indicators (Class 2 indicators) are given in ISO 11140-3, ISO 11140-4, and ISO 11140-5.

2 Normative references

The following referenced documents are indispensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies.

ISO 8601, Data elements and interchange formats—Information interchange—Representation of dates and times

ISO 11138 (all parts), Sterilization of health care products—Biological indicator systems

ISO 11607, Packaging for terminally sterilized medical devices

ISO 184721, Sterilization of health care products—Biological and chemical indicators—Test equipment

3 Terms and definitions

For the purposes of this document, the following terms and definitions apply.

3.1 bleed: Lateral migration of the indicator agent beyond the margins within which the indicator agent was applied.

3.2 critical variable: Parameters identified as being essential to the sterilization process (and requiring monitoring).

3.3 endpoint: Point of the observed change as defined by the manufacturer occurring after the indicator has been exposed to specified stated values.

3.4 graduated response: Progressive observable change occurring on exposure to one or more process variables allowing assessment of the level achieved.

1 To be published.

2 © 2005 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 11140-1:2005

3.5 indicator: Combination of the indicator agent and its substrate in the final form in which it is intended to be used (see Annex E).

NOTE—An indicator system in combination with a specific test load is also termed an indicator.

3.6 indicator agent/indicator reagent: Active substance(s) or combination of substances (see Annex E).

3.7 indicator system: Combination of the indicator agent and its substrate subsequently intended to be used in combination with a specific test load.

3.8 off-set: Transfer of indicator agent to a material in intimate contact with the surface of the indicator.

3.9 parameter: Specified value for a process variable.

3.10 penetration: Migration of the indicator agent through the substrate to the surface opposite the one to which the indicator agent was applied.

3.11 saturated steam: Water vapor in a state of equilibrium between condensation and evaporation.

3.12 stated value (SV): Value or values of a critical variable at which the indicator is designed to reach its endpoint as defined by the manufacturer.

3.13 substrate: Carrier or support material onto which the indicator is applied (see Annex E).

3.14 variable: Condition within a sterilization process, changes that alter microbicidal effectiveness.

3.15 visible change: Change defined by the manufacturer, which can be seen in the indicator after exposure to one or more critical variables of the process.

NOTE—Visible change is used to describe the response of Class 1 process indicators.

4 Classification

4.1 General

In subsequent parts of ISO 11140, indicators are classified by their intended use. The chemical indicators described in this part of ISO 11140 are classified into six groups. The chemical indicators within each of these classifications are further subdivided by the sterilization process for which they are designed to be used. The classification structure used is solely to denote the characteristics and intended use of each type of indicator when used as defined by the manufacturer. This classification has no hierarchical significance.

4.2 Class 1: Process indicators

Process indicators are intended for use with individual units (e.g., packs, containers) to indicate that the unit has been directly exposed to the sterilization process and to distinguish between processed and unprocessed units. They shall be designed to react to one or more of the critical process variables (see Tables 1–6).

4.3 Class 2: Indicators for use in specific tests

Class 2 indicators are intended for use in specific test procedures as defined in relevant sterilizer/sterilization standards.

NOTE—The requirements for specific test indicators (Class 2 indicators) are provided in other parts of ISO 11140.

4.4 Class 3: Single variable indicators

A single variable indicator shall be designed to react to one of the critical variables (see 5.2) and is intended to indicate exposure to a sterilization process at a stated value (SV) of the chosen variable (see 5.7 and 5.8).

4.5 Class 4: Multi-variable indicators

A multi-variable indicator shall be designed to react to two or more of the critical variables (see 5.2) and is intended to indicate exposure to a sterilization cycle at SVs of the chosen variables (see 5.7 and 5.8).

4.6 Class 5: Integrating indicators

Integrating indicators shall be designed to react to all critical variables. The SVs are generated to be equivalent to, or exceed, the performance requirements given in the ISO 11138 series for BIs (see Clauses 11, 12, and 13).


4.7 Class 6: Emulating indicators

Emulating indicators are cycle verification indicators which shall be designed to react to all critical variables for specified sterilization cycles. The SVs are generated from the critical variables of the specified sterilization process.

5 General requirements

5.1 The requirements given in this clause shall apply to all indicators unless specifically excluded or amended in a subsequent clause or part of ISO 11140.

5.2 For the different sterilization processes, the following variables are defined as being critical:

• STEAM Time, temperature, and water (as delivered by saturated steam)

• DRY HEAT Time and temperature

• ETHYLENE OXIDE Time, temperature, RH, and ethylene oxide (EO) concentration

• IRRADIATION Total absorbed dose

• STEAM-FORMALDEHYDE Time, temperature, water (as delivered by saturated steam) and formaldehyde concentration

• VAPORIZED HYDROGEN Time, temperature, hydrogen peroxide concentration, and, if applicable, plasma PEROXIDE

5.3 The manufacturer shall establish, document, and maintain a formal quality system to cover all operations required by this standard.

NOTE—ISO 9001 and ISO 13485 describe requirements for quality systems for design, manufacture, and testing.

5.4 Each indicator shall be clearly marked with the type of process for which it is intended to be used (see 5.6 and 5.7), with the class of indicator (see Clause 4), and for Class 3, 4, 5, and 6 indicators, with the SVs.

Where the size or format of the indicator does not permit this information to be stated in a font of 6 characters per centimeter or larger, the information shall be provided on the label and/or instructions for use.

5.5 The indicator shall comply with the requirements of this part of ISO 11140 for the duration of the shelf life as specified by the manufacturer.

(See Annex A)

5.6 Abbreviated descriptions of the process shall be in accordance with the following symbols:

STEAM — all steam sterilization processes

DRY — all dry heat sterilization processes

EO — all ethylene oxide sterilization processes

IRRAD — all ionizing radiation sterilization processes

FORM — all steam/formaldehyde sterilization processes

VH2O2 — all vaporized hydrogen peroxide sterilization processes

These descriptions are symbols and should not be translated.


5.7 If the indicator is designed for use in specific sterilization cycles, this information shall be stated or coded on the indicator, e.g.,

STEAM 121 °C 15 min

(See 3.12 and 5.6.)

5.8 Each package of indicators or the technical information leaflet supplied with the package shall provide the following information:

a) the change that is intended to occur; and for color change indicators where the color change cannot be adequately described, samples of the expected color range for both changed and unchanged indicators;

b) the critical variable(s) to which the indicator will respond, and where applicable, their SVs;

c) the class (see Clause 4), process (see 5.6), and intended use (see 5.7) for which the indicator is designed;

d) the storage conditions, before and after use;

e) the expiry date, or the manufacturing date plus shelf life, under the specified storage conditions, expressed in accordance with ISO 8601 (e.g., YYYY-MM);

f) a unique code (e.g., lot number) to provide traceability;

g) instructions for use essential to ensure proper functioning of the indicator;

h) any interfering substances that are likely to be encountered, or conditions that are likely to occur, during the intended use of the indicator and which are known to affect adversely the performance of the indicator;

i) any safety precautions required during and/or after use;

j) the manufacturer’s or supplier’s name and address;

k) the nature of any change that can occur when completely/incompletely changed indicators are stored according to the manufacturer’s instructions.

NOTE—National or regional regulation could contain additional or different requirements.

5.9 The manufacturer shall retain documentary evidence that the indicator, when used as intended by the manufacturer, does not release any substance known to be toxic in sufficient quantities to cause either a health hazard, or a hazard to the intended properties of the product being sterilized before, during, or after the sterilization process for which it is designated.

6 Performance requirements

6.1 General

6.1.1 The condition of the indicator after exposure to a sterilization process, during which all of the variables met or exceeded the specified level to produce a visible change, graduated response, or endpoint, shall remain unchanged for a period of not less than six months from the date of use, when stored under the conditions specified by the indicator manufacturer.

6.1.2 Incompletely changed indicators can deteriorate on storage, either returning to the unchanged condition or slowly completing the change reaction. If such deterioration can occur, this information should be stated in the technical information supplied by the manufacturer [see 5.8 (k)].

6.2 Class 1 indicators

6.2.1 The visible change that occurs after exposure of the indicator shall be clearly observable and shall be either from light to dark, dark to light, or shall be from one color to a distinctly different color (see Clause 8).

6.2.2 When printed onto single-use packaging material complying with ISO 11607, the indicator agent shall not bleed or off-set to such an extent that it compromises the utility of the indicator or presents a hazard for the use of the packaging material. Penetration shall not occur before, during, or after the sterilization process for which it is designed, when tested according to the method given in 7.2 (see also 5.9).


6.3 Class 2 indicators

Specific requirements for Class 2 indicators are given in Parts 3, 4, and 5 of ISO 11140.

6.4 Classes 3, 4, 5, and 6 indicators

6.4.1 The endpoint which occurs after exposure of the indicator to the SVs of critical variables shall be clearly observable and shall be either from light to dark, dark to light, or shall be from one color to a distinctly different color.

6.4.2 The indicator agent shall not off-set or penetrate the substrate to which it is applied, or materials with which it is in contact before, during, or after the sterilization process for which it is designed, when tested according to the method given in 7.2 (see also 5.9).

7 Test methods

7.1 General

Tests for compliance with the requirements given in Clauses 6 and 7 through 14 of this part of ISO 11140 shall be carried out by exposing the indicators to the conditions specified and using equipment complying with ISO 18472, then examining the indicator for compliance.

Specific test methods for irradiation indicators are not given. Performance requirements are given in 8.5.

NOTE 1—Test equipment and methods for Class 2 indicators are contained in Parts 3, 4, and 5 of ISO 11140.

7.2 Off-set (transference)

Place a second layer of a similar substrate to that of the indicator in intimate contact with indicator reagent. Process the indicator in the sterilization process, as stated by the indicator manufacturer. Visually inspect the indicator, its substrate, and the second layer of substrate, before and after processing, for compliance with 6.2.2 or 6.4.2.

7.3 Procedure—Steam indicators

7.3.1 Load the indicator on a suitable sample holder. The sample holder shall not affect the performance of the indicator.

The sample holder should allow the indicator to be exposed to the test conditions in the manner specified by the indicator manufacturer. Different indicators may require different sample holder designs. Consult the indicator manufacturer for guidance.

7.3.2 Before initiating a test cycle, the inner surface of the resistometer shall be heated to the required temperature.

7.3.3 With the loaded sample holder in the resistometer, carry out the following sequence of operations:

a) Evacuate the resistometer to 4.5 kPa ± 0.5 kPa within 2 min. [manufacturers of chemical indicators may choose to specify the use of a different depth of vacuum; if they do so, this information shall be included in each package of indicators, or in the technical information leaflet supplied with each package (see 5.8)].

b) Admit steam to the resistometer to obtain the required test temperature in 10 s or less.

c) Maintain the conditions for the required exposure time.

d) At the end of the exposure period, evacuate the resistometer to 10 kPa or less within 1 min, then admit air to ambient pressure.

7.3.4 Immediately remove the indicator from the resistometer and visually examine for compliance. Record the result.

The indicator should be removed from the resistometer as quickly as possible to avoid prolonged exposure to process-critical variables during testing.

7.4 Procedure—Dry heat indicators




7.4.2 Preheat the resistometer to the required test temperature.

7.4.3 Place the loaded sample holder into the resistometer, close the access port, and initiate the process cycle. The time required to achieve the required temperature at the surface of the indicator within the resistometer shall not exceed 1 min.

7.4.4 Maintain the conditions for the required exposure time.

7.4.5 At the end of the exposure period, immediately remove the samples from the resistometer and cool to 100 °C or less in a period not exceeding 1 min.



7.5 Procedure—EO indicators

7.5.1 Load the indicator onto a suitable sample holder. The sample holder shall not affect the performance of the indicator.


7.5.2 Before initiating a test cycle, the sample, sample holder, and the inner surface of the resistometer shall be equilibrated to the required temperature.

7.5.3 With the loaded sample holder in the resistometer, carry out the following sequence of operation:

a) Evacuate the resistometer to 10 kPa ± 0.5 kPa [manufacturers of chemical indicators may choose to specify the use of a different depth of vacuum; if they do so, this information shall be included in each package of indicators, or in the technical information leaflet supplied with each package (see 5.8)].

b) Admit sufficient water vapor to raise the RH in the resistometer to the required level.

c) Admit ethylene oxide to the required ethylene oxide concentration in 1 min or less. (For the zero gas exposure cycle, no ethylene oxide should be admitted. If applicable, the diluent gas should be admitted to the working pressure. This test should not be carried out in a vessel where traces of ethylene oxide may be present.)

d) Maintain these conditions for the required exposure time.

5) At the end of the exposure period, reduce the EO concentration surrounding the indicator to a level that will no longer affect the indicator, within 1.5 min.



7.6 Procedure—Steam-formaldehyde indicators

NOTE—See Annex D.

7.6.1 Prepare an aqueous solution of formaldehyde at a concentration of 1 mol/L ± 0.01 mol/L. The formaldehyde concentration of this solution shall be established by the use of a validated analytical method.

7.6.2 Pre-heat the formaldehyde solution to 60 °C ± 0.5 °C.




7.6.4 Immerse the indicator, loaded onto the sample holder, in the formaldehyde solution.

Ensure that the indicators are completely immersed in the formaldehyde solution and do not float to the surface.

7.6.5 Maintain these conditions for the required exposure time.

7.6.6 At the end of the exposure period, reduce the formaldehyde concentration surrounding the indicator to a level that will no longer affect the indicator, within 1.5 min. Visually examine the indicator for compliance. Record the result.

The indicator should be removed from the formaldehyde solution as quickly as possible.

7.7 Procedure—Vaporized hydrogen peroxide indicators



7.7.2 Before initiating a test cycle, the sample, sample holder, and the inner surface of the resistometer shall be equilibrated to the required temperature.

7.7.3 With the loaded sample holder in the resistometer, carry out the following sequence of operations:

a) If required, admit sufficient water vapor to raise the RH in the resistometer to the required level.

b) Admit vaporized hydrogen peroxide to the required test condition concentration within less than 2 s (for an exposure time of 0 minutes, no hydrogen peroxide should be admitted).

c) Maintain these conditions for the required exposure time.

d) At the end of the exposure period, reduce the hydrogen peroxide concentration surrounding the indicator to a level that will no longer affect the indicator.



8 Additional requirements for process (Class 1) indicators

8.1 Process indicators printed or applied onto packaging material

Process indicators may be printed on packaging material or presented as self-adhesive labels, pouches, packaging tapes, tags, insert labels, etc.

8.2 Process indicators for steam sterilization processes

Following exposure to the specified test conditions, the process indicator shall perform as shown in Table 1.

Table 1—Test and performance requirements for Class 1 process indicators for

Test environment Test time Test temperature

No change or a change that is markedly different from the visible change as specified by the manufacturer

Visible change as specified by the manufacturer

Saturated steam 3.0 min ± 5 s 121 °C (+3/0 °C) Acceptable result Unacceptable result

Saturated steam 10.0 min ± 5 s 121 °C (+3/0 °C) Unacceptable result Acceptable result

Saturated steam 0.5 min ± 5 s 134 °C (+3/0 °C) Acceptable result Unacceptable result

Saturated steam 2 min ± 5 s 134 °C (+3/0 °C) Unacceptable result Acceptable result

Dry heat 30 min ± 1 min 140 °C (+2/0 °C) Acceptable result Unacceptable result

STEAM


NOTE—The dry heat test is designed to ensure that process indicators for steam require the presence of steam in order to respond.

8.3 Process indicators for dry heat sterilization processes



Test environment Test time Test temperature



Dry heat 20 min ± 1 min 160 °C +5/0 °C Acceptable result Unacceptable result

Dry heat 40 min ± 1 min 160 °C +5/0 °C Unacceptable result Acceptable result

8.4 Process indicators for ethylene oxide sterilization processes


The absence of EO gas test should be carried out in the absence of residual EO gas. If a color change occurs without the apparent presence of ethylene oxide, the complete absence of EO gas may need to be verified.


Test environment Test time

Test temperature RH %

Gas concentration mg/L



Absence of EO gas

90 min ± 1 min 60 °C ± 2 °C ≥ 85 % None Acceptable result

Unacceptable result

5 min ± 15 s 30 °C ± 1 °C EO gas

Test at: 2 min ± 15 s 54 °C ± 1 °C

60 % ± 10 % RH

600 mg/L ± 30 mg/L

Acceptable result

Unacceptable result

30 min ± 15 s 30 °C ± 1 °C EO gas

Test at: 20 min ± 15 s 54 °C ± 1 °C

60 % ± 10 % RH

600 mg/L ± 30 mg/L

Unacceptable result

Acceptable result

NOTE—The reaction of some ethylene oxide indicators can be impaired by the presence of carbon dioxide or other gas. Where the formulation is such that this could occur, the indicator should be tested in a system employing not less than 80 % carbon dioxide or other gas in admixture with ethylene oxide [see 5.8 (h)].

DRY

EO


8.5 Process indicators for irradiation sterilization processes



Test environment Intensity

Peak wavelength

Absorbed dose Test time



Ultraviolet radiation

≥ 3.3 W/m2 254 nm N/A 120 min ± 5 min

Acceptable result

Unacceptable result

Ionizing radiation

N/A N/A 1 kGy ± 0.1 kGy

N/A Acceptable result

Unacceptable result

Ionizing radiation

N/A N/A 10 kGy ± 1 kGy

N/A Unacceptable result

Acceptable result

The ultraviolet radiation test is designed to ensure that the indicator will not respond to non-ionizing radiation such as inadvertent exposure to sunlight. A mercury vapor lamp has been shown to deliver the suitable peak wavelength.

8.6 Process indicators for steam-formaldehyde sterilization processes

8.6.1 Following exposure to the specified test conditions, the process indicator shall perform as shown in Table 5.

The absence of formaldehyde test should be carried out in the absence of residual formaldehyde. If a color change occurs without the apparent presence of formaldehyde, complete absence of formaldehyde may need to be verified.

Table 5—Test conditions and performance requirements for Class 1 process indicators for

Test condition Test time Test temperature

Gas concentration



Absence of formaldehyde

90 min ± 1 min 80 °C ± 2 °C None Acceptable result Unacceptable result

Formaldehyde 20 s ± 5 s 60 °C ± 0.5 °C 1.0 mol/L ± 0.01 mol/L

Acceptable result Unacceptable result

Formaldehyde 15 min ± 15 s 70 °C ± 2 °C 1.0 mol/L ± 0.01 mol/L

Unacceptable result Acceptable result

8.6.2 For indicators produced for steam-formaldehyde sterilization cycles operating at temperatures below 55 °C or above 65 °C, the tests described in Table 5 shall be carried out at the maximum temperature and formaldehyde concentration specified by the manufacturer of the indicator.

NOTE—The manufacturer might need to perform additional functional tests on the indicator using a low-temperature steam-formaldehyde process in order to demonstrate suitability for that particular process (see 5.7, 5.8, and Annex D).

IRRAD

FORM


8.7 Process indicators for vaporized hydrogen peroxide sterilization processes

Following exposure to the specified test conditions, the process indicators shall perform as shown in Table 6.

The absence of hydrogen peroxide test should be carried out in the absence of residual hydrogen peroxide. If a color change occurs without the apparent presence of hydrogen peroxide, complete absence of hydrogen peroxide may need to be verified.

Table 6—Test conditions and performance requirements for Class 1 process indicators for

Test condition Test time Test temperature Gas concentration



45 min ± 5 min

50 °C ± 0.5 °C None Absence of hydrogen peroxide

Test at: 45 min ± 5 min

27 °C ± 0.5 °C None


7 s ± 1 s 50 °C ± 0.5 °C 2.3 mg/L ± 0.4 mg/L Hydrogen peroxide

Test at: 10 s ± 1 s 27 °C ± 0.5 °C 2.3 mg/L ± 0.4 mg/L


6 min ± 1 s 50 °C ± 0.5 °C 2.3 mg/L ± 0.4 mg/L Hydrogen peroxide

Test at: 10 min ± 1 s

27 °C ± 0.5 °C 2.3 mg/L ± 0.4 mg/L

Unacceptable result Acceptable result

9 Additional requirements for single variable (Class 3) indicators

9.1 Single variable indicators shall be designed for one of the critical variables to be monitored, as listed in 5.2.

9.2 Single variable indicators tested at the SV (Test Point 1) shall reach the endpoint (see Table 7).

9.3 Single variable indicators tested at the SV minus the tolerance (Test Point 2) shall not reach the endpoint (see Table 7).

10 Additional requirements for multi-variable (Class 4) indicators

10.1 Multi-variable indicators shall be designed for two or more of the critical variables to be monitored, as listed in 5.2.

10.2 Multi-variable indicators tested at the SV (Test Point 1) shall reach the endpoint (see Table 7).

10.3 Multi-variable indicators tested at the SV minus the combined tolerances (Test Point 2) shall not reach the endpoint (see Table 7).

10.4 Multi-variable indicators for steam and steam-formaldehyde, tested at the time and temperature SVs in dry heat, i.e., absence of moisture, but with all other parameters at the SVs, shall not reach the endpoint (see Table 7).

NOTE—The dry heat test is designed to ensure that multi-variable indicators for steam and steam-formaldehyde require the presence of steam in order to respond.

VH2O2


Table 7—Test and performance requirements for Class 3 and Class 4 indicators

Sterilization process Test pointa Test time Test temperature Sterilizing agent concentration mg/L RH %

Steam 1

2

SV 0 %

SV –25 %

SV 0 °C

SV –2 °C

Dry heat 1

2

SV 0 %

SV –25 %

SV 0 °C

SV –5 °C

Ethylene oxide 1

2

SV 0 %

SV –25 %

SV 0 °C

SV –5 °C

SV 0 %

SV –25 %

> 30 %

> 30 %

Steam-formaldehyde 1

2

SV 0 %

SV –25 %

SV 0 °C

SV –3 °C

SV 0 %

SV –20 %

NOTE—For examples of testing multi-variable (Class 4) indicators, see Annex B.

a Test Point 1: The indicator, when tested at the SV, shall reach its endpoint.

Test Point 2: The indicator, when tested at all SVs minus the combined tolerances, shall not reach its endpoint.

11 Additional requirements for steam integrating (Class 5) indicators NOTE—See Annex C.

11.1 Integrating indicators for steam processes shall undergo an endpoint indicating exposure to a steam sterilization cycle at defined variables within the relevant tolerances given in 11.2 and 11.10.

11.2 The SV at 121 °C shall be specified and shall be not less than 16.5 min.

11.3 Upon exposure to saturated steam at 121 °C ± 0.5 °C to a time equal to the SV at 121 °C, the integrator shall have reached or exceeded its endpoint (pass condition).

11.4 Upon exposure to saturated steam at 121 °C ± 0.5 °C to a time equal to 63.6 % of the SV at 121 °C, the integrator shall not have reached its endpoint (fail condition).

11.5 The endpoint shall be determined in dry saturated steam at 135 °C ± 0.5 °C and at one or more equally spaced temperature test points in the range of 121 °C to 135 °C. The time to reach the endpoint at these temperatures shall be the SVs (determined) given by the manufacturer (see 5.8).

11.6 The integrator temperature coefficient shall be determined from the slope of the curve created by plotting log SV and/or SV (determined) versus temperature.

NOTE—The manufacturer’s SVs at these additional temperatures can be used to determine the integrator temperature coefficient.

11.7 The integrator temperature coefficient shall be not less than 6 °C and not more than 14 °C, and the correlation coefficient of the curve established by least squares linear regression analysis of the data shall be not less than 0.9.

11.8 Upon exposure to saturated steam at 135 °C ± 0.5 °C to a time equal to 63.6 % of the SV at 135 °C (determined), the integrator shall not reach its endpoint (fail condition).

11.9 Upon exposure to saturated steam at the temperatures as used in 11.5 at a time equal to 63.6 % of the SV (determined), the integrator shall not reach its endpoint (fail condition).

11.10 Upon exposure to dry heat at 137 °C +1 °C for 30 min + 0 min, the endpoint shall not be reached.

11.11 The manufacturer shall state clearly any factors that can adversely affect the efficacy of the sterilization process but which are not detected by the indicator, or not detected in a manner that will give assurance of satisfactory attainment of that critical variable [see 5.8 (h)].

NOTE—Some regulatory authorities require that demonstration of the performance of a steam integrator be conducted in parallel with an appropriate BI.


12 Additional requirements for dry heat integrating (Class 5) indicators

12.1 Integrating indicators for dry heat processes shall undergo a clearly detectable change indicating exposure to a dry heat sterilization cycle at defined variables within the relevant tolerances given in 12.2 and 12.9.

12.2 The SV at 160 °C shall be specified and shall be more than 30 min.

12.3 Upon exposure to dry heat at 160 °C ± 1.5 °C to a time equal to the SV at 160 °C, the integrator shall have reached or exceeded its endpoint (pass condition).

12.4 Upon exposure to dry heat at 160 °C ± 1.5 °C to a time equal to 63.6 % of the SV at 160 °C, the integrator shall not have reached its endpoint (fail condition).

12.5 The endpoint shall be determined in dry heat at 180 °C ± 1.5 °C and at one or more of the following temperatures: 140 °C ± 1.5 °C; 170 °C ± 1.5 °C. The time to reach the endpoint at these temperatures shall be the SVs (determined) given by the manufacturer.

12.6 The integrator temperature coefficient shall be determined from the slope of the curve created by plotting log SV and/or SV (determined) versus temperature.

NOTE—The manufacturer’s SVs at these additional temperatures can be used to determine the integrator temperature coefficient.

12.7 The integrator temperature coefficient shall be not less than 20 °C and not more than 40 °C, and the correlation coefficient of the curve established by least squares linear regression analysis of the data shall be not less than 0.9.

12.8 Upon exposure to dry heat at 180 °C ± 1.5 °C to a time equal to 63.6 % of the SV at 180 °C (determined), the integrator shall not reach its endpoint (fail condition).

12.9 Upon exposure to dry heat at the temperatures of 140 °C ± 1.5 °C or 170 °C ± 1.5 °C as used in 12.5 at a time equal to 63.6 % of the SV (determined), the integrator shall not reach its endpoint (fail condition).

12.10 The manufacturer shall state clearly any factors of which it is aware that can adversely affect the efficacy of the sterilization process but which are not detected by the indicator, or not detected in a manner that will give assurance of satisfactory attainment of that critical variable [see 5.8 (h)].

NOTE—Some regulatory authorities require that demonstration of the performance of a dry heat integrator be conducted in parallel with an appropriate BI.

13 Additional requirements for ethylene oxide integrating (Class 5) indicators NOTE—See Annex C.

13.1 Integrating indicators for ethylene oxide processes shall undergo a clearly detectable change indicating exposure to an ethylene oxide sterilization cycle at defined variables within the relevant tolerances given in 13.2 and 13.5.

13.2 The SV at 54 °C ± 0.5 °C, 600 mg EO/L ± 30 mg/L EO/L, and 60 % relative humidity (RH) ± 10 % RH shall be at least 30 min, and/or the SV at 37 °C ± 0.5 °C, 600 mg/L EO/L ± 30 mg/L EO/L, and 60 % RH ± 10 % RH shall be at least 90 min (see 5.7 and 5.8).

13.3 Upon exposure to an ethylene oxide process of 54 °C ± 0.5 °C, 600 mg EO/L ± 30 mg/L EO/L, and 60 % RH ± 10 % RH to a time equal to the SV, and upon exposure to EO/L 37 °C ± 0.5 °C, 600 mg EO/L ± 30 mg/L EO/L, and 60 % RH ± 10 % RH to a time equal to the SV, the integrator shall reach its endpoint (pass condition).

13.4 Upon exposure to an ethylene oxide process of 54 °C ± 0.5 °C, 600 mg EO/L ± 30 mg/L EO/L, and 60 % RH ± 10 % RH to a time equal to 66.7 % of the SV, and upon exposure to 37 °C ± 0.5 °C, 600 mg EO/L ± 30 mg/L EO/L, and 60 % RH ± 10 % RH to a time equal to 66.7 % of the SV, the integrator shall not reach its endpoint (fail condition).

13.5 Upon exposure to 54 °C ± 0.5 °C and 60 % RH ± 10 % RH to a time equal to the SV in the absence of ethylene oxide, and upon exposure to 37 °C ± 0.5 °C and 60 % RH ± 10 % RH to a time equal to the SV in the absence of ethylene oxide, the integrator shall not reach its endpoint (fail condition).

NOTE—Some regulatory authorities require that demonstration of the performance of an EO integrator be conducted in parallel with an appropriate BI.


13.6 The manufacturer shall state clearly any factors of which it is aware that can adversely affect the efficacy of the sterilization process but which are not detected by the indicator, or not detected in a manner that will give assurance of satisfactory attainment of that critical variable [see 5.8 (h)].

14 Additional requirements for emulating (Class 6) indicators

14.1 Emulating indicators shall be designed for all critical variables for the process listed in 5.2 and undergo an endpoint indicating exposure to a sterilization cycle at defined variables within the relevant tolerances given in Table 8.

14.2 Emulating indicators tested at the SV (Test Point 1) shall reach the endpoint (pass condition).

14.3 Emulating indicators tested at the SV minus the combined tolerances (Test Point 2) shall not reach the endpoint (fail condition).

14.4 Emulating indicators for steam exposed to dry heat at 137 °C +1/−0 °C for 30 min +1/−0 min shall not reach the endpoint.

NOTE—The dry heat test is designed to ensure that emulating indicators for steam require the presence of steam in order to respond.

14.5 The manufacturer shall state clearly any factors of which it is aware that can adversely affect the efficacy of the sterilization process but which are not detected by the indicator, or are not detected in a manner that will give assurance of satisfactory attainment of that critical variable [see 5.8 (h)].

Table 8—Test and performance requirements for Class 6 indicators

Sterilization process Test pointa Test time (minutes) Test temperature

Gas concentration mg/L RH %

Steam 1

2

SV 0 %

SV –6 %

SV 0 °C

SV –1 °C

Dry heat 1

2

SV 0 %

SV –20 %

SV 0 °C

SV –1 °C

Ethylene oxide 1

2

SV 0 %

SV –10 %

SV 0 °C

SV –2 °C

SV 0 %

SV 15 %

> 30 %

> 30 %

NOTE—For an example of testing emulating (Class 6) indicators, see Annex B.

a Test Point 1: The indicator, when tested at the SV, shall reach its endpoint (pass condition).

Test Point 2: The indicator, when tested at all SVs minus the combined tolerances, shall not reach its endpoint (fail condition).


Annex A (informative)

Method for demonstrating shelf life of the product

A.1 Product testing to determine shelf life should be performed in accordance with a written protocol. The protocol should be established before the commencement of the study. The protocol should specify requirements for sample size, sampling method, and data evaluation.

NOTE—National or regional regulation can contain additional or different requirements. Compliance with quality management standards (in particular ISO 9001 and ISO 13485) could require additional or different provisions.

A.2 Product samples should be stored in their normal packaging at, or above, the maximum temperature and RH recommended for storage. These conditions should be controlled and monitored.

A.3 All performance attributes should maintain the original specifications throughout the shelf life.

A.4 All results of the storage trial should be retained for a period of the shelf life plus one year from completion of the trial. After this period, a summary report should be retained for as long as the product is commercially available.


Annex B (informative)

Examples of testing indicators

B.1 Example of testing single variable (Class 3) indicator for dry heat processes

An indicator with a stated value at 160°C.

The manufacturer will denote this indicator’s performance by identifying the Stated Value (SV) of 160 °C (see 5.8). When tested at 160 °C (SV, Test Point 1), using the test methods specified in this part of ISO 11140, the indicator shall reach its endpoint. When tested at 155 °C (SV minus tolerance, Test Point 2) (see NOTE), the indicator shall not reach its endpoint. There is no requirement to test the indicator between Test Point 1 and Test Point 2; however, if the indicator were to be tested between Test Point 1 and Test Point 2, it may produce an ambiguous result (i.e., the indicator may reach its endpoint or it may not reach its endpoint).

NOTE—With reference to Table 7, the tolerance on the test temperature for a Class 3 single-variable indicator is −5 °C. Therefore, 160 °C – 5 °C = 155 °C, which becomes Test Point 2.

B.2 Example of testing multi-variable indicator for steam processes

An indicator with a stated value at 121°C and 15 min.

The manufacturer will denote this indicator’s performance by identifying the SVs of 121 °C and 15 min (see 5.7 and 5.8). The manufacturer may also give additional SVs for the product at different temperatures and times. When tested at 121 °C for 15 min (SV, Test Point 1), using the test methods specified in this part of ISO 11140, the indicator shall reach its endpoint. When tested at 119 °C for 11 min 15 s (SV minus both temperature and time tolerances or Test Point 2) the indicator shall not reach its endpoint (see NOTE). There is no requirement to test the indicator between Test Point 1 and Test Point 2; however, if the indicator were to be tested between Test Point 1 and Test Point 2, it can produce an ambiguous result (i.e., the indicator could reach its endpoint or not reach its endpoint).

NOTE— With reference to Table 7, the tolerance on the test temperature for a Class 4 multi-variable indicator is −2 °C, and the tolerance on the test time is −25 % (25 % of 15 min is 3 min 45 s). Therefore, 121 °C – 2 °C = 119 °C and 15 min − 3 min 45 s = 11 min 15 s, which becomes Test Point 2.

B.3 Example of testing integrating (Class 5) indicators

Test procedures and background for integrating indicators are found in Annex C.

B.4 Example of testing emulating (Class 6) indicators for steam processes

An indicator with a stated value at 134°C and 3.5 min.

The manufacturer will denote this by clearly identifying the SVs of 134 °C and 3.5 min (see 5.7 and 5.8). The manufacturer may also give additional SVs for the product at different temperatures and times. When tested at 134 °C for 3.5 min (SV, Test Point 1), using the test methods specified in this part of ISO 11140, the indicator shall reach its endpoint. When tested at 133 °C for 3 min 17 s (SV minus both tolerances or Test Point 2) the indicator shall not reach its endpoint (see NOTE). There is no requirement to test the indicator between Test Point 1 and Test Point 2; however, if the indicator were to be tested between Test Point 1 and Test Point 2, it can produce an ambiguous result (i.e., the indicator could reach its endpoint or not reach its endpoint).

NOTE— With reference to Table 8, the tolerance on the test temperature for a Class 6 emulating indicator is −1 °C, and the tolerance on the test time is −6 % (6 % of 3 min 30 s is 12.6 s [round up to 13 s)]. Therefore, 134 °C − 1 °C = 133 °C and 3 min 30 − 13 s = 3 min 17 s, which becomes Test Point 2.


Annex C (informative)

Rationale for the requirements for integrating indicators and the link to the requirements for biological indicators (BIs) specified in ISO 11138 and microbial inactivation

C.1 Steam

C.1.1 Introduction

Integrating indicators are designed to respond in a similar manner to that of a BI when exposed to the critical variables of a sterilization process. For the purposes of this document, the performance of integrating indicators is linked to the minimum requirements for a BI for moist heat sterilization as defined in ISO 11138-3. The following provides background information and a detailed rationale for the requirements for Class 5 integrating indicators specified in Clause 11.

C.1.2 Background information

ISO 11138-3 specifies that a BI for moist heat sterilization processes shall have a D121 of not less than 1.5 min, a minimum population of 1 × 105, and a z value greater than 6. The z value for many species of Geobacillus stearothermophilus is often nearer to 10 (ISO 14161). Theoretical calculations relating to validation of moist heat processes, e.g., Fo, normally use a z of 10 (Pflug, 1999[18]).

The performance of a BI may also be defined by the survivor kill window (SKW) which, at 121 °C and based on the minimum values specified above, would typically be: survives 4.5 min and is killed in 13.5 min. The SKW is calculated from:

Survival time = (log P – 2) × D121;

Kill time = (log P + 4) × D121;

where

log is the log to the base ten of the number;

P is the nominal population; and

D121 is the decimal reduction time at 121 °C in minutes.

C.2 The link between the integrator stated value (SV) and BI inactivation

In order to achieve an inactivation of at least 1 × 10−6 in populations of microorganisms, it would be necessary to expose a BI with a D121 = 1.5 min and a population of 1 × 105 to a temperature of 121 °C for 16.5 min.

Thus:

(log 105 – log 10−6) × 1.5 = 16.5 min

Thus, for a Class 5 integrator, the minimum SV, i.e., the time at which the endpoint is reached at 121 °C, is required to be not less than 16.5 min. By requiring a minimum SV of 16.5 min, a direct relationship is established between the integrator endpoint and a satisfactory inactivation level in an equivalent BI and therefore the objective of a terminal sterilization process.

In the case where the manufacturer specifies an SV at 121 °C greater than 16.5 min, a greater inactivation level will have been achieved (and therefore a greater safety factor) by the time the indicator reaches its endpoint. Nevertheless, when tested, the integrator should reach or exceed its endpoint when exposed for a time equal to the SV.

The above represents the pass or accept condition for the integrator.

Regarding the fail condition, theoretically a single BI will show no growth when the exposure time is sufficient to reduce the population to less than one surviving organism. However, when actual BIs are in use, the exposure time has to be greater than that specified above because of the natural variation associated with biological systems.


Typically, if 50 or more BIs are tested, then an exposure time that reduces the population to a theoretical level of less than 10−2 would be required to eliminate any positives for growth (ISO 14161). The determination of the SKW provides an indication of how much more exposure time is required. Thus an exposure period of (log P + 4) × D is used to define the kill time, i.e., a further 4 log reduction past the point of one surviving organism per unit, i.e., 1 × 10−4. Thus, it can be anticipated that some BIs would show positive for growth at a 10−2 exposure level but none at a 10−4 exposure level.

Adopting these criteria for the definition of the fail response in an integrating indicator at 121 °C with a population of 105 and a D value of 1.5, a 7 log reduction is required to reach the 10−2 level. The exposure time required for this is:

(log P + 2) × D = 10.5 min

Thus, the integrating indicator should not reach its endpoint when exposed to dry saturated steam at 121 °C for 10.5 min. However, the manufacturer’s SV at 121 °C may be greater than 16.5 min, in which case the exposure conditions required to create a failure or reject response in the integrator must be linked to the manufacturer’s SV and be at least 10.5 min. Using 10.5 min as a baseline for failure and 16.5 min as a baseline for a pass:

5.165.10 = 0.636

Thus, for an indicator with an SV greater than 16.5 min, the fail condition at which it is tested should be an exposure time which is 63.6 % of its SV. Thus, the indicator must show a fail or reject response when exposed to dry saturated steam at 121 °C for 63.6 % of the SV.

In comparison to a BI, the SV of the integrator is related to the time required to achieve an 11 log reduction in population. 63.6 % of the SV is related to the time required to achieve a 7 log reduction in population. Thus, the D value of a BI complying with ISO 11138-3 is related to the SV of the integrator through the following:

(log P + 6) × D = SV;

(5 + 6) × 1.5 = 16.5;

i.e., an 11 log reduction in population to an inactivation level of 1 × 10−6.

Therefore

D = 6) (log

SV+P

= 11SV

In a BI, survivors will be observed when the exposure time (survivor time, ST) is

(log P + 2) × D = ST

substituting for D:

(log P + 2) × 11SV = ST

Now

log P + 2 = 7

Therefore:

7 × 11SV = ST


Therefore

SV × 117 = SV × 0.636 = ST

Thus, for the integrator, the survivor time, i.e., the fail response in the integrator, and hence the time when the endpoint must not be reached, is 63.6 % of the SV.

C.3 Comparison with the requirements for integrating indicators in ISO 11140-1:1995

ISO 11140-1:1995 requires that an integrator shall show a fail response when exposed to its SV minus 1 °C on temperature and minus 15 % on time. For an integrator with an SV of 16.5 min at 121 °C, a fail condition should be observed when the indicator is exposed to 120 °C for 14.025 min. Relating this to a BI response if the BI has a D121 of 1.5 and a z of 10 °C, then the D at 120 °C will be:

D120 = D121 × 10−[(T1−Tref ) / 10)]

where

D120 is the D value at 120 °C;

D121 is the D value at 121 °C;

T1 is the working temperature (in this case 120 °C);

Tref is the reference temperature (in this case, 121 °C)

D120 = 1.5 × 10−[(120−121)/10] = 1.88 miutes.

Assuming the BI has a population of 1 × 105, then the log reduction achieved by exposing the BI at 120 °C for 14.025 minutes would be:

1.88

14.025 = 7.427

i.e., a 7.4 log reduction.

Thus, the log survivor level in the BI would be

5 – 7.427 = −2.427.

Therefore, the surviving population will be

1 × 10−2.427 = 3.7 × 10−3.

This is very close to the requirements specified in this version of ISO 11140-1, i.e., that an integrator should show a fail when the exposure time creates a 7 log reduction in population, i.e., down to 1 × 10−2.

Thus, the proposed requirements listed above are broadly similar to the previous requirements for the example cited above.

Considering a BI with a z of 6, the D value at 120 °C will be given by:

D120 = 1.5 × 10−[(120−121)/6] = 2.2 minutes


Assuming the BI has a population of 1 × 105, then log reduction by exposing the BI at 120 °C for 14.025 min would be:

2.2

14.025 = 6.375.

Thus, the survivor level in the BI would be:

5 – 6.375 = −1.375 = 4.6 × 10−2

Considering a BI with a z of 14:

D120 = 1.5 × 10−[(120−121)/14] = 1.7681

Assuming the BI has a population of 1 × 105, then the log reduction by exposing the BI at 120 °C for 14.025 min would be:

1.7681 14.025 = 7.93.

Thus, the survivor level in the BI would be:

5 – 7.93 = −2.9 = log (1.25 × 10−3)

In summary of the above, see Table C.1.

Table C.1—BI survivor level

z = 6 z = 10 z = 14

BI survivor level 4.6 × 10−2 3.7 × 10−3 1.25 × 10−3

Examining the same data at the maximum temperature:

If the integrator has an SV at 135 °C and 0.66 min. BI with a D121 of 1.5, population of 1 × 105, and z of 10 then the D at 135 °C will be:

D135 = 1.5 × 10–[(135−121)/10] = 0.06 min.

For the pass or accept condition, an 11 log reduction is achieved in

11 × 0.06 minutes = 0.66 min.

For the fail or reject condition, a 7 log reduction is achieved in

7 × 0.06 = 0.42 min.

According to our requirements, the integrator should show a fail at SV × 63.6 %:

0.66 × 0.636 = 0.42 min.

Using the previously defined criteria for a fail condition:

SV temperature – 1 °C and SV time − 15 % would mean a fail at 134 °C and 0.56 min.


For the BI

D134 = 1.5 × 10–[(134−121)/10] = 0.075 min

Thus, exposure for 0.56 min would bring about a log reduction of

0.075

0.56 = 7.45 log reduction

Therefore, the survivor level would be

5 – 7.45 = −2.45 = log (3.5 × 10−3)

Which is again close to the acceptance level for fail stated above, i.e., 1 × 10−2.

C.4 Ethylene oxide

ISO 11138-2 specifies that an ethylene oxide (EO) BI shall have a D value of not less than 2.5 min at 54 °C, 60 % RH, and 600 mg EO/L with a maximum population of 1 × 106. The performance of the BI may be defined by the survivor kill window which would typically be: survives at least 10 min, killed in no more than 25 min at 54 °C based on the minimum values specified above. The SKW can be calculated from:

Survival time = (log P – 2) × D

Kill time = (log P + 4) × D

It is common to aim for a final probability of survival in a population of microorganisms of 10−6 before a product can be labeled sterile.

Based on the above information, it would be necessary to expose a BI with a D = 2.5 and a population of 1 × 106 to a temperature of 54 °C, 600 mg EO/L, and 60 % RH for 30 min in order to achieve an inactivation level of 10−6.

Thus

(log 106 − log 10−6) × 2.5 = 30 min

Thus, for a Class 5 integrator, the minimum SV, i.e., the time at which the endpoint is reached, should not be less than 30 min in order to assure that an adequate inactivation factor has been achieved in an equivalent BI.

In the case when the SV at 54 °C, 600 mg EO/L, and 60 % RH is greater than 30 min, then clearly a greater inactivation level will have been achieved by the time the indicator reaches its endpoint. Nevertheless, the integrator should reach or exceed its endpoint when exposed for a time equal to the SV.

The above represents the pass condition; Below represents the fail condition.

Theoretically, a single BI will show no growth when the exposure time is sufficient to reduce the population to less than one surviving organism. However, when actual BIs are in use, the exposure time has to be greater than that specified above because of the natural variation associated with biological systems. Typically, if 50 or more BIs were tested, then an exposure time which reduces the population to a theoretical level of less than 10−0 would be required to eliminate most positives for growth. This is reflected in the determination of the survival/kill characteristics where an exposure period of (log P + 4) × D is used to define the kill time, i.e., a further 4 log reduction past the point of one surviving organism per unit, i.e., 1 × 10−4. Thus, we might expect to see some BIs showing positive for growth at a 10−0 exposure level but none at a 10−4 exposure level. Adopting these criteria for the definition of the fail response in an integrating indicator at 54 °C, 600 mg EO/L, and 60 % RH with a population of 1 × 106 and a D value of 2.5, an 8 log reduction is required to reach the 10−2 level. The exposure time required for this is:

(log P + 2) × D = 20 min


Thus, the integrating indicator should not reach its endpoint when exposed to 600 mg EO/L and 60 % RH at 54 °C for 20 min or less. However, the manufacturer’s SV at 54 °C may be greater than 30 min; therefore, the fail condition must be linked to this value and be at least 20 min. Using 20 min as a baseline for failure and 30 min as a baseline for a pass:

3020 = 0.667

Thus, for an indicator with an SV greater than 30 min, the fail condition at which it is tested should be an exposure time which is 66.7 % of its SV. Thus the indicator must show a fail response when exposed to 600 mg EO/L and 60 % RH at 54 °C for 66.7 % of the SV.

In biological terms, the SV is related to the time required to achieve a 12 log reduction in population; 66.7 % of the SV is related to the time required to achieve an 8 log reduction.


Annex D (informative)

Rationale for the liquid-phase test method for steam-formaldehyde indicators

D.1 General

In order to test indicators in a reproducible manner, specific test equipment (resistometers) and methods are used. For the low-temperature steam-formaldehyde process, it is extremely difficult to create a stable formaldehyde gas concentration in a resistometer, since defined amounts of formaldehyde injected into a vessel will dissolve in the small amounts of water (condensate) droplets present. The concentration of formaldehyde in this water is 1,000 to 10,000 times higher in concentration than in the gas phase, depending on the temperature (Gömann, et al.).[9]

It is for this reason that ISO 11138-5 utilizes a liquid-phase test method where the formaldehyde concentration is clearly defined and allows reproducible conditions.

D.2 The low-temperature steam-formaldehyde process

Even with constant steam conditions and stable formaldehyde gas concentrations, the sterilization process heavily depends upon the design of the sterilizer chamber and the nature of the load. The formaldehyde sterilization process can be considered simplistically in two steps:

a) as in steam sterilization processes, an aqueous condensate film is created on the surface of the load; this condensation will occur very rapidly;

b) since the concentration of formaldehyde at equilibrium between the gas and liquid phases is extremely different (1:1,000–10,000), the time taken for this equilibrium to occur will be relatively long. In practical situations, this may require a time frame from 10 min up to 2 h.

The lethality of the sterilization process thus depends heavily on the formaldehyde concentration in the liquid phase, i.e., surface condensate. It may be very difficult to determine in absolute terms the time taken for these equilibrium conditions to be achieved.

D.3 Chemical indicators

For chemical indicators that do not have water-soluble components, it is desirable to utilize a similar liquid-phase test method, for the reasons given above. However, for chemical indicators which do have water-soluble components, the indicators may have to be tested and calibrated in the gas phase, using BIs in conformance to ISO 11138-5, as a process reference, and in a steam-formaldehyde sterilizer. This will also apply to indicators other than Class 1 indicators.


Annex E (informative)

Relationship of indicator components

Key

1 indicator (re) agent

2 substrate

3 indicator, e.g., class 1, 3, 4, 5, 6

4 indicator system

5 specific test load

6 indicator, e.g., class 2


Bibliography

[1] EN 285, Sterilization—Steam sterilizers—Large sterilizers.

[2] EN 550, Sterilization of medical devices—Validation and routine control of ethylene oxide sterilization.

[3] EN 552, Sterilization of medical devices—Validation and routine control of sterilization by irradiation.

[4] EN 554, Sterilization of medical devices—Validation and routine control of sterilization by moist heat.

[5] EN 556-1, Sterilization of medical devices—Requirements for medical devices to be designated “STERILE”—Part 1: Requirements for terminally sterilized medical devices.

[6] EN 1422, Sterilizers for medical purposes—Ethylene oxide sterilizers—Requirements and test methods.

[7] EN 14180, Sterilizers for medical purposes—Low temperature steam and formaldehyde sterilizers—Requirements and testing.

[8] EN 45014, General criteria for supplier’s declaration of conformity (ISO/IEC Guide 22:1996).

[9] GÖMANN J, KAISER U, and MENZEL R. Reaction kinetics of the low-temperature-steam-formaldehyde (LTSF) sterilization process. Central Service, ZentrSteril, 8 (5) 2000, pp. 290–296.

[10] ISO 9001:2000, Quality management systems—Requirements.

[11] ISO 11135:1994, Medical devices—Validation and routine control of ethylene oxide sterilization.

[12] ISO 11137:1995, Sterilization of health care products—Requirements for validation and routine control—Radiation sterilization.

[13] ISO 1113485, Medical devices—Quality management systems—Requirements for regulatory purposes.

[14] ISO 14161, Sterilization of health care products—Biological indicators—Guidance for the selection, use and interpretation of results.

[15] ISO 5882, Sterilization of health care products—Chemical indicators—Guidance for selection, use and interpretation of results.

[16] ISO 17665, Sterilization of health care products—Moist heat—Development, validation and routine control of a sterilization process for medical devices.

[17] ISO/IEC 17025, General requirements for the competence of testing and calibration laboratories.

[18] PFLUG IJ. Microbiology and engineering of sterilization processes, 10th edition. Environmental Sterilization Laboratory, 1920 South First Street, Minneapolis, MN 55454, USA 1999.

[19] RUSSELL AD. The destruction of bacterial spores. London: Academic Press, 1982.

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