© ISO 2017 Sterilization of health care products — Biological indicators — Part 4 Biological indicators for dry heat sterilization processes Stérilisation des produits de santé — Indicateurs biologiqu[.]
INTERNATIONAL STANDARD ISO 11138-4 Second edition 2017-03 Sterilization of health care products — Biological indicators — Part 4: Biological indicators for dry heat sterilization processes Stérilisation des produits de santé — Indicateurs biologiques — Partie 4: Indicateurs biologiques pour la stérilisation la chaleur sèche Reference number ISO 11138-4:2017(E) © ISO 2017 ISO 11138-4:2017(E) COPYRIGHT PROTECTED DOCUMENT © ISO 2017, Published in Switzerland All rights reserved Unless otherwise specified, no part o f this publication may be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior written permission Permission can be requested from either ISO at the address below or ISO’s member body in the country o f the requester ISO copyright o ffice Ch de Blandonnet • CP 401 CH-1214 Vernier, Geneva, Switzerland Tel +41 22 749 01 11 Fax +41 22 749 09 47 copyright@iso.org www.iso.org ii © ISO 2017 – All rights reserved ISO 11138-4:2017(E) Contents Page Foreword iv Introduction v Scope Normative references Terms and definitions General requirements Test organism Suspension Carrier and primary packaging Inoculated carriers and biological indicators Population and resistance (normative) Method for determination of resistance to dry heat sterilization Annex B (normative) Calculation of z value Annex A Bibliography © ISO 2017 – All rights reserved iii ISO 11138-4:2017(E) Foreword ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISO member bodies) The work o f 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 o f electrotechnical standardization The procedures used to develop this document and those intended for its further maintenance are described in the ISO/IEC Directives, Part In particular the different approval criteria needed for the di fferent types o f ISO documents should be noted This document was dra fted in accordance with the editorial rules of the ISO/IEC Directives, Part (see www.iso org/directives) Attention is drawn to the possibility that some o f the elements o f this document may be the subject o f patent rights ISO shall not be held responsible for identi fying any or all such patent rights Details o f any patent rights identified during the development o f the document will be in the Introduction and/or on the ISO list of patent declarations received (see www.iso org/patents) Any trade name used in this document is in formation given for the convenience o f users and does not constitute an endorsement For an explanation on the voluntary nature o f standards, the meaning o f ISO specific terms and expressions related to formity assessment, as well as in formation about ISO’s adherence to the World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see the following URL: www.iso org/iso/foreword html This document was prepared by Technical Committee ISO/TC 198, Sterilization of health care products This second edition cancels and replaces the first edition (ISO 11138-4:2006), which has been technically revised A list of all the parts of ISO 11138 can be found on the ISO website iv © ISO 2017 – All rights reserved ISO 11138-4:2017(E) Introduction ISO 11138-1 specifies production, labelling, test methods and per formance requirements for the manufacture of biological indicators including inoculated carriers and suspensions intended for use in validation and monitoring sterilization processes This document gives specific requirements for those biological indicators intended for use in dry heat sterilization processes The ISO 11138 series represents the current “state-of-the-art” according to the experts representing not to promote the use of biological indicators where such use is not advised, but to provide common manu facturers, users and regulatory authorities involved in developing the standard The intent is requirements for the production o f those biological indicators that are known to be in use today A standard exists providing general requirements for the validation and control o f dry heat sterilization processeses (see ISO 20857) NOTE It is possible that some countries or regions have published other standards covering requirements for sterilization or biological indicators Advice on selection, use and interpretation of results when using biological indicators can be found in ISO 14161 © ISO 2017 – All rights reserved v INTERNATIONAL STANDARD ISO 11138-4:2017(E) Sterilization of health care products — Biological indicators — Part 4: Biological indicators for dry heat sterilization processes Scope for T his cument s peci fies requirements tes t organis ms , s us pens ions , ino culated carriers , biological indicators and test methods intended for use in assessing the performance of sterilization processes employing dr y heat as the s teri lizing agent at s teri li zing temperatures within the range o f °C to 18 °C NO TE Re qu i rements for va l id ation NO TE Re qu i rements for T he a nd control o f d r y he at s ter i l i z atio n p ro ce s s e s a re p rovide d b y I S O work p l ace s a fe ty c a n b e pro vide d b y n ation a l or re gio n a l re gu l ation s Normative references fol lowi ng c u ments are re ferre d to i n the tex t i n s uch a way th at s ome or a l l o f thei r content s titute s re qu i rements o f th i s c u ment For date d re ference s , on ly the e d ition cite d appl ie s For u ndate d re ference s , the late s t e d ition o f the re ference d c ument (i nclud i ng a ny amend ments) appl ie s ISO 11138-1:2017, requirements Sterilization of health care products — Biological indicators — Part 1: General ISO 18472, Sterilization of health care products — Biological and chemical indicators — Test equipment Terms and definitions For the pu r p o s e s o f th i s c u ment, the term s and defi nition s given i n I S O 11 -1 apply ISO and IEC maintain terminological databases for use in standardization at the following addresses: — IEC Electropedia: available at http://www.electropedia org/ — ISO Online browsing platform: available at https://www.iso org/obp/ General requirements T he re qu i rements o f I S O 11 -1 apply 5.1 Test organism The test organisms shall be spores of Bacillus atrophaeus or other strains of microorganisms of demo ns trated equivalent p er fo rmance as required by this cument NOTE Some strains of Bacillus subtilis © ISO 2017 – All rights reserved h ave b e en re cl a s s i fie d a s Bacillus atrophaeus ISO 11138-4:2017(E) NOTE Bacillus atrophaeus CIP 77.18, NCIMB 8058, DSM 675, NRRL B-4418 and ATCC 9372 or Bacillus subtilis, DSM 13019 have been found to be suitable1) 5.2 If a test organism other than Bacillus atrophaeus is used, the suitability o f the resistance o f that test organism shall be determined Suspension The requirements o f ISO 11138-1 apply Carrier and primary packaging 7.1 The suitability o f the carrier and primary packaging materials for biological indicators for use in dry heat sterilization processes shall be demonstrated in accordance with the requirements o f ISO 11138-1:2017, 5.2 and Annex B The exposure conditions to determine compliance shall be the following: 7.2 a) minimum exposure temperature: greater than or equal to °C above the manu facturer’s stated maximum temperature; b) sterilizing agent: dry heat in ambient air; c) maximum exposure temperature: as stated by the manu facturer; i f not stated by the manu facturer, the maximum exposure temperature shall be greater than or equal to 180 °C; d) exposure time: greater than or equal to 30 NOTE These conditions have been selected to represent a realistic challenge to the carrier while remaining within the practical limits o f a dry heat sterilization process Inoculated carriers and biological indicators The requirements o f ISO 11138-1 apply 9.1 Population and resistance The manu facturer shall state the resistance characteristics according to ISO 11138-1:2017, 6.4 The viable count shall be stated with increments less than or equal to 0,1 × 10 per unit (e.g per ml of suspension, per inoculated carrier or per biological indicator) 9.2 n For inoculated carriers and biological indicators, the viable count shall be greater than or equal to 1,0 × 10 9.3 The resistance shall be expressed as the D value in minute at 160 °C The D value of each batch/lot o f biological indicators or inoculated carriers shall be stated in minutes to one decimal place at 160 °C 9.4 9.5 Suspensions, inoculated carriers or biological indicators containing Bacillus atrophaeus spores shall have a D160 value of not less than 2,0 when tested according to the conditions in Annex A Other microorganisms shall have D values supporting the application The z value of the test organisms in the suspension, on the inoculated carrier or in the biological indicator shall be determined at not less than 1) These are examples o f suitable products available commercially This information is given for the convenience o f users o f this document and does not constitute an endorsement by ISO o f these products © ISO 2017 – All rights reserved ISO 11138-4:2017(E) three temp eratures , in the range o f °C to °C Thes e data s hall b e us ed to calculate the which s hall b e greater than o r equal to °C (s ee 9.6 Annex B) z value, The res is tance characteris tics s p ecified in this cument and any o ther cument s hall b e defined us ing the s p ecific critical variab les as s o ciated with the re ferenced s terilizatio n p ro ces s values are determined according to methods given in ISO 11138-1:2017, Annexes C and D 9.7 D 9.8 Determination of D value and survival-kill response characteristics require the use of a resistometer Annex A) ap p lying the re ference res is to meter p ro ces s p arameters (s ee NO TE T he va lue s s tate d ab ove wo u ld fit a d r y he at s ter i l i z er with force d a i r d i s tr ib ution , r u n n i ng a c ycle o f 16 ° C with a hold i n g ti me o f h 9.9 The survival-kill window should be calculated using the formulae in ISO 11138-1:2017, Annex E NOTE This information can be of value to the user when comparing different batches from the same manufacturer EXAMPLE Using the formulae in ISO 11138-1:2017, Annex E, with the minimum population and minimum D va lue re qu i rements s p e c i fie d i n th i s c u ment, the s u r viva l-ki l l re s p o n s e ch a rac ter i s tic s a re — at 16 ° C : s u r viva l ti me gre ater th a n o r e qu a l to m i n a nd ki l l ti me le s s th a n o r e qu a l to m i n © ISO 2017 – All rights reserved ISO 11138-4:2017(E) Annex A (normative) Method for determination of resistance to dry heat sterilization A.1 Principle This method requires the use of a test apparatus referred to as a resistometer in this document The f f in ISO 18472 A.2 s p e c i fic ation s o the re s i s tome ter pro ce s s p a rame ters or d r y he at s teri l i z ation pro ce s s e s are provide d Sp e ci fic re qu i rements relate d to the te s t me tho d are provide d i n A.2 Procedure A.2.1 Load the samples on to suitable sample holders NOTE Preconditioning of the samples according to the manufacturer’s recommendations have been found to provide more consistent results A.2.2 Preheat the res is to meter chamb er to the required o p erating temp erature, e g °C ± °C A.2.3 Place the lo aded s amp le ho lders in the chamb er, clo s e the chamb er and initiate the tes t cycle A.2.4 C arry o ut the — fo llo wing s equence o f o p eratio ns : s tep : mai ntai n the ab ove cond ition s for the re qu i re d hold i ng ti me ± s; — step 2: at the end of the exposure period, remove the test samples from the chamber and cool down rapid ly Tra n s fer the s a mple s to the grow th me d iu m a nd i nc ub ate (s e e I S O 11 -1 : 017, C lau s e ) A.2.5 The transfer period shall be documented and the same time period shall be used for all tests A.3 Determination of resistance Resistance characteristics shall be determined according to the methods given in ISO 11138-1:2017, Annexes C, D and E © ISO 2017 – All rights reserved ISO 11138-4:2017(E) Annex B (normative) Calculation of z value Using all the data obtained from either ISO 11138-1:2017, Annex C or D, plot the log10 of the D value against exposure temperature in degrees Celsius The z value is equal to the negative reciprocal of B.1 the s lo p e o f the b es t- fit rectilinear curve as determined by regres s io n analys is NOTE B.2 See 9.5 for requirements regarding calculation of z va lue a nd co e ffic ient o f de ter m i n atio n , The s lo p e o f the b es t- fit rectilinear curve is calculated us ing m= where m n t γ G A B C (nG) − ( AB) (nC) − ( A ) r Formula (B.1): (B.1) i s the slop e o f the b e s t-fit re c ti l i ne ar c u r ve; is the number of D value/temperature pairs; is the exposure time; is the minimum D value; = ∑ t ( lo g = ∑ (t ) ; = ∑( =∑ lo g 10 10 ( 2) ; y y) ; ); t The data required for the calculation are given in Table B.1 © ISO 2017 – All rights reserved ISO 11138-4:2017(E) Table B.1 — Examples of data collected for regression analysis D Exposure temperature value (min) log10 y t t2 t3 tn log10 y1 log10 y2 log10 y3 log10 yn (t1) (t2 ) (t3 ) (tn) i=n i=n i=n (° C ) y t y2 y3 yn y t ti ∑ i =1 A= Assigned variable ∑ i= lo g 10 yi C = (log10y) (log10 y1) t2 (log10 y2 ) t3 (log10 y3 ) tn (log10 yn) (log10y1) (log10 y2 ) (log10 y3 ) (log10 yn) (t i ) ∑ i= t t 1 A Table B.2 B.3 B= (log10 y) B i=n ∑ ( G = t i i= C s hows examp le calculatio ns fo r lo g 10 ) i=n y i E = ( ∑ i= lo g 10 yi G ) E the s lo p e o f the b es t- fit rectilinear curve Table B.2 — Examples of calculations for slope D Exposure temperature value (min) log10 y (° C ) y t = 4,2 y2 = 2,1 y3 = 1,2 = 150 t2 t3 = 170 y = , 62 = 16 = 256 00 ) = ,4 i =3 ti ∑ i= B= Assigned variable A (log10 y) t log10 y1 (t1) = 225 00 t1 (log10 y1) = 93,480 (log10 y1) = 0,388 log10 y2 = 0,322 (t2 ) t2 (log10 y2 ) = 51,552 (log10 y2 ) = 0,103 log10 y3 = 0,079 (t3 ) = 289 00 t3 (log10y3 (log10 y3 ) t A= (log10 y) t i= ∑ i= lo g 10 yi C = B= (t i ) ∑ i= 1 = 480 i =3 ,024 C = 77 000 i= ∑ ( G = t i i= lo g 10 G= ,49 ) = 0,006 i= y i E = ( ∑ i= E lo g 10 yi ) = 0,498 (nG) − ( AB) (nC) − ( A ) (3 ) (158 496 ) − ( 480 ) (1 024 ) = (3 ) (77 000 ) − 480 ) ( m= , m m= m , = ( 475, 488 ( )−( )−( 231 000 − 16 320 491, 808 230 400 ) ) , 600 m = − 027 , © ISO 2017 – All rights reserved ISO 11138-4:2017(E) The z value is equal to the negative reciprocal of the slope obtained and is calculated using Formula (B.2): B.4 z value =− m (B.2) 1 Using the above calculated slope, the resulting z value is: z = − = 36 764 − 027 , ° C rou nde d to one de ci ma l p oi nt , z= B.5 6, °C The co e fficient o f determinatio n, Formula (B.3): r2 , fo r the linearity o f the G ) − ( A) ( B n ) } ( { r = (C ) − ( A n ) ( E ) − ( B n ) z value curve is calculated using where a l l vari able s are as defi ne d i n B.6 E xamp le calculatio ns are given below NO TE fo r (B.3) B.2 and E = ∑ ( lo g 10 ) y the co e fficient o f determinatio n fo r the linearity, r2 , of the z value curve C a lc u l ation s re fle c t rou nd i ng Using the values from Table B.2, r {( − ( ) ( ) ) } = −( −( ( ( ) ) ) ) ( )−( ) = ) − ( ) ( ) − ( ) ( (− ) = ( )( ) 158,496 480 77 000 r 158,496 77 000 r r r 5, 440 76 800 480 1,024 0,498 1,024 163,936 0,498 0, 9 200 0, 148 = 29, 593 29, 720 = 995 , © ISO 2017 – All rights reserved ISO 11138-4:2017(E) Bibliography [1] ISO 14161, Sterilization of health care products — Biological indicators — Guidance for the selection, use and interpretation of results [2] ISO 20857, Sterilization of health care products — Dry heat — Requirements for the development, [3] Angelotti Appl Environ Influence of Spore Moisture Content on the Dry-Heat Resistance of Bacillus subtilis var New Microbiol 1968 May, 16 (5) pp 735–745 D rummond D.W., & P f lug I.J Dry-heat destruction of Bacillus subtilis spores on surfaces: effect o f humidity in an open system Appl Microbiol 1970 Nov, 20 (5) pp 805–809 [4] validation and routine control of a sterilization process for medical devices © ISO 2017 – All rights reserved ISO 11138-4:2017(E) ICS 1 080.01 Price based on pages © ISO 2017 – All rights reserved