© ISO 2017 Sterilization of health care products — Biological indicators — Part 3 Biological indicators for moist heat sterilization processes Stérilisation des produits de santé — Indicateurs biologi[.]
INTERNATIONAL STANDARD ISO 11138-3 Third edition 2017-03 Sterilization of health care products — Biological indicators — Part 3: Biological indicators for moist heat sterilization processes Stérilisation des produits de santé — Indicateurs biologiques — Partie 3: Indicateurs biologiques pour la stérilisation la chaleur humide Reference number ISO 11138-3:2017(E) © ISO 2017 ISO 11138-3:2017(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 11138-3:2017(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 moist heat sterilization Annex B (normative) Calculation of z value and coe fficient o f determination, r2 Annex A Bibliography © ISO 2017 – All rights reserved iii ISO 11138-3:2017(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 third edition cancels and replaces the second edition (ISO 11138-3:2006), which has been technically revised A list of all parts of ISO 11138 can be found on the ISO website iv © ISO 2017 – All rights reserved ISO 11138-3:2017(E) Introduction T h i s c u ment s p e c i fie s pro duc tion, lab el l i ng , te s t me tho d s and p er forma nce re qu i rements for the manufacture of biological indicators including inoculated carriers and suspensions intended for use f f those biological indicators intended for use in moist heat sterilization processes i n va l idation and mon itori ng o s teri l i z ation pro ce s s e s T h i s c ument give s s p e ci fic re qu i rements or M oi s t he at as the s teri l i z i ng agent i s defi ne d i n th i s c u ment as d r y s atu rate d s te a m Wh i le r- s te am mixtures can be used in moist heat sterilization processes, the methods and performance requirements of this document might not be applicable for biological indicators used in such processes The ISO 11138 series represents the current “state-of-the-art” according to the experts representing f not to promote the use of biological indicators where such use is not advised, but to provide common manu ac tu rers , u s ers and regu lator y authoritie s i nvolve d i n developi ng the s tandard T he i ntent i s re qu i rements for the pro duc tion o f tho s e biolo gic a l i nd ic ators known to b e i n u s e to day Standards exist providing requirements for the validation and control of moist heat sterilization (see ISO 17665 series) 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 11138-3:2017(E) Sterilization of health care products — Biological indicators — Part 3: Biological indicators for moist heat sterilization processes Scope T h i s c u ment s p e c i fie s re qu i rements for te s t organ i s m s , s u s p en s ion s , i no c u l ate d c arriers , biolo gic a l indicators and test methods intended for use in assessing the performance of sterilization processes employi ng moi s t he at a s the s teri l i z i ng agent for va l idatio n a nd control o f moi s t he at s ter i l i z ation pro ce s s e s a re pro vide d b y the NO TE Re qu i rements NO TE N ation a l or re gio n a l re g u l ation s c a n pro vide re qu i rements ISO 17665 series T he for work p l ace s a fe ty 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 http://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 Geobacillus stearothermophilus or other strains of micro o rganis m o f demo ns trated equivalent p er fo rmance as required by this cument NOTE Bacillus stearothermophilus h a s b e en re cl a s s i fie d a s Geobacillus stearothermophilus © ISO 2017 – All rights reserved ISO 11138-3:2017(E) NOTE Geobacillus stearothermophilus ATCC 7953 (NCTC 10007, DSM 22 and CIP 52.81), ATCC 12980 (equivalent to NRRL B-4419) have been found to be suitable1) [1][2] If a test organism other than Geobacillus stearothermophilus or Bacillus subtilis ATCC 35021 (5230) 5.2 is us ed, the s uitab ility o f the res is tance o f that tes t o rganis m s hall b e determined NOTE For processes at less than 121 °C, microorganisms such as Bacillus subtilis ATCC 35021 (5230) could b e u s e d , p a r tic u l a rl y i n s teri l i z ation o f he at- s en s iti ve l iqu id s Suspension T he re qui rements o f I S O 11 -1 apply 7.1 Carrier and primary packaging The s uitab ility o f the carrier and p rimary p ackaging materials fo r b io lo gical indicato rs fo r us e in moist heat sterilization processes shall be demonstrated in accordance with the requirements of ISO 11138-1:2017, 5.2 and Annex B The exposure conditions to determine compliance shall be a) minimum exposure temperature: greater than or equal to °C above the manufacturer’s stated maximum exposure temperature, 7.2 b) s teri l i z i ng agent: d r y s aturate d s te am; i f the biolo gic a l i nd ic ator i s i ntende d for u s e i n a moi s t he at pro ce s s no t u s i ng d r y s atu rate d s te am, e g an r/s te am m i xtu re, the appropri ate a i r s te a m mixture should be used and noted as an exception to this document, c) ma xi mum exp o s u re temp eratu re: as s tate d by the ma nu fac tu rer; i f no t s tate d b y the ma nu fac turer, a temperature of 140 °C shall be used, and 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 of a moist heat sterilization process Inoculated carriers and biological indicators T he re qui rements o f I S O 11 -1 apply Population and resistance The manufacturer shall state the resistance characteristics in accordance with ISO 111381:2017, 6.4 9.1 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 1) Thes e are examp les o f s uitab le p ro ducts availab le co mmercially This in fo rmatio n is given fo r the co nvenience o f us ers o f this cument and es no t co ns titute an endo rs ement by I S O o f thes e p ro ducts © ISO 2017 – All rights reserved ISO 11138-3:2017(E) The resistance shall be expressed as the D value in minutes at 121 °C Additional temperature(s) D value of each batch/lot of biological indicators or inoculated carriers shall be stated in minutes to one decimal place at 121 °C 9.4 may b e s elected by the manu facturer The 9.5 Suspensions inoculated carriers or biological indicators containing Geobacillus stearothermophilus spores shall have a D121 value of greater than or equal to 1,5 when tested according to the conditions given 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 three temperatures, in the range of 110 °C to 138 °C These data shall be used to calculate the z value, which shall be greater than or equal to °C (see Annex B) , 9.6 The res is tance characteris tics s p ecified in this cument and any o ther p art o f I S O 1 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 requires the use of a Annex A) res is to meter ap p lying the re ference res is to meter p ro ces s p arameters (s ee 9.9 The survival-kill window can 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 121 °C: survival time greater than or equal to 4,5 and kill time less than or equal to 13,5 © ISO 2017 – All rights reserved ISO 11138-3:2017(E) Annex A (normative) Method for determination of resistance to moist heat sterilization A.1 Principle This method requires the use of a test apparatus referred to as a resistometer in this document The specifications o f the resistometer process parameters for moist heat sterilization processes are provided in ISO 18472 Specific requirements related to the test method are provided in A.2 A.2 Procedure A.2.1 Load the test samples on to suitable sample holders A.2.2 Pre-heat the resistometer chamber to the required operating temperature, e.g 121 °C ± 0,5 °C A.2.3 Place the loaded sample holders in the chamber, close the chamber and initiate the test cycle A.2.4 Carry out the following sequence o f operations: — Step 1: Evacuate the chamber to a set point of 4,5 kPa ± kPa within — Step 2: Admit steam to the chamber to obtain the required temperature and pressure within 10 s For the minute exposure time, no steam shall be admitted — Step 3: Maintain these conditions for the required exposure time — Step 4: At the end o f the exposure period, evacuate the chamber; then admit filtered air to ambient pressure The time taken to achieve 100 kPa shall be 10 s or less — Step 5: At the end o f the above test cycle, remove the samples from the chamber, and cool down rapidly Trans fer the samples to the growth medium and incubate (see ISO 11138-1:2017, Clause 7) 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 methods given in ISO 11138-1:2017, Annexes C, D and E © ISO 2017 – All rights reserved ISO 11138-3:2017(E) Annex B (normative) Calculation of z v a l u e a n d c o e f f i c i e n t o f d e t e r m i n a t i o n , r2 B.1 Using all the data obtained from either ISO 11138-1:2017, Annex C or ISO 11138-1:2017, Annex D, plot the log10 of the D value against exposure temperature in degrees Celsius The z value is equal to the negative recipro cal o f 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 G A B C t ( nG ) − ( AB ) ( nC ) − ( A ) r Formula (B.1): (B.1) i s the s lop 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 ∑ t ( y ) = ∑ (t ) =∑ ( y) = lo g 10 va lue/temp eratu re p rs; ; ; lo g = 10 ∑ (t ) ; ; i s exp o s ure ti me; is minimum D value The data required for the calculation are given in Table B.1 γ © ISO 2017 – All rights reserved ISO 11138-3:2017(E) Table B.1 — Examples of data collected for regression analysis D Exposure temperature value (min) t y2 y3 yn t2 t3 tn y t i =n t log10 y1 log10 y2 log10 y3 log10 yn (t1) (t2 ) (t3 ) (tn) i =n A = ∑ ti B=∑ i =1 Assigned variable i= lo g 10 yi A Table B.2 B.3 log10 y (°C) y (log10 y) (log10 y) (log10 y1) t2 (log10 y2 ) t3 (log10 y3 ) tn (log10 yn) (log10 y1) (log10y2 ) (log10 y3 ) (log10 yn) 2 i =n t C = ∑ (ti ) t i =1 B i =n G=∑ i= t i ( C s hows examp le calculatio ns fo r lo g 10 ) y i i =n E = ∑( log i =1 G 10 yi ) 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 = 2,0 y2 = 1,1 y3 = 0,4 = 121 t2 = 124 t3 = 129 y = − 0,397 i =3 i= A = ∑ ti B=∑ i =1 A (log10 y) t log10 y1 = 0,301 (t1) = 146 41 t1 (log10 y1) = 36,421 log10 y2 = 0,041 (t2 ) = 153 76 t2 (log10y2 ) = 5,133 log10 y3 (t3 ) = 166 41 t3 (log10 y3 t Assigned variable (log10 y) t i= = 374 B= lo g 10 yi −0,055 ) = − 51 , i =3 C = ∑ (ti ) i =1 C = 46 658 i= G = ∑ t i ( i= G= lo g 10 y i ) − 9,7 74 (log10 y1) = 0,090 (log10 y2 ) = 0,001 (log10 y3 ) = 0,158 i= E = ∑( i= E lo g 10 yi ) = 0,250 ( nG ) − ( AB ) ( nC ) − ( A ) ( ) ( − 774 ) − ( 374 ) ( − 055 ) m = ( ) ( 46 658 ) − 74 ) ( m= , ( −29 323 ) − ( −20 757 ) (139 974 ) − (139 876 ) , m = m = m = − 0, 087 , , − 8, 566 98 © ISO 2017 – All rights reserved ISO 11138-3:2017(E) The z value is equal to the negative reciprocal of the slope obtained and is calculated using the Formula (B.2): B.4 z value 1 = −1 m (B.2) using the above calculated slope, the resulting z value is: z z B.5 = 11, 441 °C rounded to one decimal point = −1 − 0, 087 = 11,4 °C The co e fficient o f determinatio n, Formula (B.3): r2 , fo r the linearity o f the z value curve is calculated using ( G ) − ( A ) ( B n ) } { r = C − A2 n E − B2 n ) ( ) ( ) ( ) ( 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 = ∑ ( y) lo g 10 the co e fficient o f determinatio n, r2 , fo r the linearity o f 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 {( − ) ( )( )} = 46 658 − 374 ,250 − − 0,055 ) ( ) ( ) ( ) ( − 9,774 − − 6,919 ) ( ) ( = ( 46 658 ) − ( 46 625 333 ) ( 0,250 ) − ( 001 ) ( − 855 ) = (32 666 )( 249 ) 9,774 − 374 - 0,055 2 2 r , , r , , r r = , 8, 153 8, 153 = 1, 000 © ISO 2017 – All rights reserved ISO 11138-3:2017(E) Bibliography [1] ISO 14161, Sterilization of health care products — Biological indicators — Guidance for the selection, use and interpretation of results [2] ISO 17665-1, Sterilization of health care products — Moist heat — Part 1: Requirements for the development, validation and routine control of a sterilization process for medical devices © ISO 2017 – All rights reserved ISO 11138-3:2017(E) ICS 1 080.01 Price based on pages © ISO 2017 – All rights reserved