1、| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | BRITISH STANDARD BS EN 12297:1998 The Euro
2、pean Standard EN 12297:1998 has the status of a British Standard ICS 07.080 07.100.01 NO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAW Biotechnology Equipment Guidance on testing procedures for sterilizabilityThis British Standard, having been prepared under the direction of th
3、e Sector Board for Materials and Chemicals, was published under the authority of the Standards Board and comes into effect on 15 September 1998 BSI 1998 ISBN 0 580 30068 4 BS EN 12297:1998 Amendments issued since publication Amd. No. Date Text affected National foreword This British Standard is the
4、English language version of EN 12297:1998. The UK participation in its preparation was entrusted to Technical Committee CII/58, Biotechnology, which has the responsibility to: aid enquirers to understand the text; present to the responsible European committee any enquiries on the interpretation, or
5、proposals for change, and keep the UK interests informed; monitor related international and European developments and promulgate them in the UK. A list of organizations represented on this committee can be obtained on request to its secretary. Cross-references The British Standards which implement i
6、nternational or European publications referred to in this document may be found in the BSI Standards Catalogue under the section entitled “International Standards Correspondence Index”, or by using the “Find” facility of the BSI Standards Electronic Catalogue. A British Standard does not purport to
7、include all the necessary provisions of a contract. Users of British Standards are responsible for their correct application. Compliance with a British Standard does not of itself confer immunity from legal obligations. Summary of pages This document comprises a front cover, an inside front cover, t
8、he EN title page, pages 2 to 11 and a back cover.CEN European Committee for Standardization Comite Europe en de Normalisation Europa isches Komitee fu r Normung Central Secretariat: rue de Stassart 36, B-1050 Brussels 1998 CEN All rights of exploitation in any form and by any means reserved worldwid
9、e for CEN national Members. Ref. No. EN 12297:1998 E EUROPEAN STANDARD EN 12297 NORME EUROPE ENNE EUROPA ISCHE NORM March 1998 ICS Descriptors: Biotechnology, medical equipment, sterilization, disinfection, contamination, micro-organisms, noxious micro-organisms, tests, safety, hygiene conditions, i
10、nspection, accident prevention, environmental protection, work safety English version Biotechnology Equipment Guidance on testing procedures for sterilizability Biotechnologie Equipement Guide des proce dures dessai pour le contro le de la capacite a la ste rilisation Biotechnik Gera te und Ausru st
11、ungen Leitfaden fu r Verfahren zur Pru fung der Sterilisierbarkeit This European Standard was approved by CEN on 2 March 1998. CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this European Standard the status of a national standard
12、without any alteration. Up-to-date lists and bibliographical references concerning such national standards may be obtained on application to the Central Secretariat or to any CEN member. This European Standard exists in three official versions (English, French, German). A version in any other langua
13、ge made by translation under the responsibility of a CEN member into its own language and notified to the Central Secretariat has the same status as the official versions. CEN members are the national standards bodies of Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Ic
14、eland, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and United Kingdom.Page 2 EN 12297:1998 BSI 1998 Foreword This European Standard has been prepared by Technical Committee CEN/TC 233, Biotechnology, the Secretariat of which is held by AFNOR. This European S
15、tandard shall be given the status of a national standard, either by publication of an identical text or by endorsement, at the latest by September 1998, and conflicting national standards shall be withdrawn at the latest by September 1998. According to the CEN/CENELEC Internal Regulations, the natio
16、nal standards organizations of the following countries are bound to implement this European Standard: Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom. Co
17、ntents Page Foreword 2 1 Scope 3 2 Definitions 3 3 Testing 4 4 Documentation 5 Annex A (informative) Guidance on selection of sterilizability testing 6 Annex B (informative) Information on test methods for sterilizability 9 Annex C (informative) Bibliography 11Page 3 EN 12297:1998 BSI 1998 1 Scope T
18、his European Standard gives guidance on general testing procedures to assess the sterilizability for micro-organisms of equipment (components and units of equipment) used in biotechnological processes. This European Standard gives guidance on the assessment of the sterilizability of biotechnological
19、 equipment with respect to a release of process micro-organisms that can affect the safety of the worker (occupational health) and/or that can have adverse effects to the environment. This European Standard is applicable to plants or components, such as valves and fittings, tanks, pumps, piping, sep
20、arating and filling devices as well as instrumentation in contact with process fluids. This European Standard applies if the intended use of the equipment includes hazardous or potentially hazardous micro-organisms. This European Standard is not applicable to testing for sterility of media and equip
21、ment prior to processing or operation, respectively. NOTE 1 For disinfection of external surfaces such as walls, working benches and floors, attention is drawn to national and European Standards. NOTE 2 For sterilization of equipment and media in autoclaves attention is drawn to national and Europea
22、n Standards such as EN 285 and EN 554 (see annex C 21, 22). 2 Definitions For the purposes of this standard, the following definitions apply. 2.1 component of equipment technical entity which forms part of a unit of equipment NOTE Examples of components of equipment are vessels, valves and sensors.
23、2.2 direct test method (in biotechnology) test method which employs micro-organisms for quantification 2.3 indirect test method (in biotechnology) test method which employs physical and/or chemical means for quantification 2.4 micro-organism any microbiological entity, cellular or non-cellular, capa
24、ble of replication or of transferring genetic material EN 1619 NOTE For the purposes of this standard, the term micro-organism covers the term of biological agent according to the Directive 90/679/EEC: micro-organisms, including those which have been genetically modified, cell cultures and human end
25、oparasites which may be able to provoke any infection, allergy or toxicity. 2.5 process micro-organism micro-organism used for production purposes in a biotechnological process or constituting (part of) the product itself 2.6 sterile state of being free from viable micro-organisms NOTE 1 In practice
26、 no such absolute statement regarding the absence of viable micro-organisms can be proven. However, sterile conditions can be regarded as established by using an accepted or recognized method of sterilization. NOTE 2 The process of inactivation of viable micro-organisms during a sterilization proced
27、ure is usually described by an empirical mathematical function, commonly an exponential function. By their mathematical nature, such functions can be reduced to very low numbers, but not to zero. However, these empirical functions can be applied to control or assess the process parameters of a steri
28、lization procedure to realize a desired degree of inactivation of viable micro-organisms. 2.7 sterilizability ability of components of equipment, units of equipment or plants to be made sterile 2.8 sterilization process used to reach a sterile state 2.9 sterilizing in place (SIP) sterilization witho
29、ut opening or dismantling of components of equipment and/or unit of equipment 2.10 target micro-organism process micro-organism and/or other micro-organisms relevant for the specific process NOTE For safety testing procedures, non-pathogenic micro-organisms should be used where possible. 2.11 unit o
30、f equipment assembly of components used to perform one or more unit operationsPage 4 EN 12297:1998 BSI 1998 3 Testing 3.1 General Testing procedures for sterilizability are required to verify whether equipment can be sterilized, so that potential risks to occupational health and/or the environment a
31、re eliminated. In particular it should be established that, for example, for maintenance work the utilized micro-organisms are inactivated to such a degree that no harm results to maintenance staff or to the environment from residual process micro-organisms. Testing procedures should be designed to
32、ensure that relevant information on sterilizability can be obtained. 3.2 Methodology To determine the sterilizability of plant and equipment choose and specify an appropriate test method or combination of test of methods (see annexes A and B): a) specify an appropriate indicator related to the propo
33、sed use of the equipment; b) select the analytical procedure to be used to determine the quantity of this indicator which is present in the equipment or plant. The appropriate biological indicator is preferably not harmful for the worker and/or the environment; c) specify a sterilization protocol in
34、cluding, as a minimum, the specification of the sterilizing agent and the mode of application; NOTE 1 Potential hazard to the operator during sterilization should be assessed. NOTE 2 Factors such as duration, temperature and dose should be included into the protocol. 3.3 Testing procedure Carry out
35、the testing procedures as follows: a) load the equipment or plant with the indicator under conditions representative of conditions during processing; b) using the analytical procedure defined in 3.2, determine the quantity of indicator substance present at the time at which sterilization procedures
36、would be applied; c) apply the sterilization protocol specified in 3.2 to the plant or equipment being tested for sterilizability; d) using the analytical procedure selected in 3.2, determine the quantity of indicator present in the equipment or plant after application of the sterilization protocol;
37、 e) using the data obtained, express the sterilizability of the equipment or plant; f) determine the appropriate sterilizability class to the equipment under test as described in the equipment standards with respect to the chosen indicator and sterilization protocol. 3.4 Choice of test methods If th
38、e results of the test method should be quickly available and with a limited amount of work involved in sterilizability demonstration runs, indirect test methods should be used. Indirect test methods may however only be applied if a validated correlation between the measured effect and the desired pe
39、rformance has been shown. When direct test methods are used, they should be carried out using appropriate controls in order to eliminate false positive results as a consequence of incorrect handling of the samples. This means that parallel to the test sample preparation another culture tube is handl
40、ed in the same way as the original sample but without inoculation as well as the inclusion of media samples which are sterilized by a validated sterilization. 3.5 Direct test methods The validation of a sterilization cycle can be done by analysis of an undiluted sample of the sterilized process medi
41、um and by performing microbiological challenge tests. Microbiological challenge tests are usually carried out by filling the equipment or component to be investigated to a representative volume with a suitable medium and adding indicator micro-organisms. This type of testing procedure is required if
42、 the indicator or process micro-organism(s) which is to be detected is present around or even below the detection limit of the test method of choice. A reliable reduction rate of indicator micro-organism can be determined whenever the number of colony forming units which can be detected is high enou
43、gh to allow the determination of statistically reliable inactivation kinetics, for example depending on the evaluation method 100 to 1 000 colony forming units/ml are required. NOTE Preferably an immobilized indicator micro-organism should be used. The efficacy of a heat sterilization is proved by t
44、he absence of process or indicator micro-organisms. Examples of appropriate indicator micro-organisms are given in the references listed in annex C 1 to 4, 9 to 12, 14. The type of micro-organism to be selected as indicator micro-organism depends on the characteristics of the process micro-organism
45、and should be representative for a worst case situation.Page 5 EN 12297:1998 BSI 1998 The choice of a specific indicator micro-organism should ensure that the degree of sterilization is measurable within a certain period of time during the sterilization procedure. In order to comply with these bound
46、ary conditions for gas sterilization procedures, e.g. ethylene oxide or formaldehyde, representative indicator micro-organism(s) should be selected (see annex C 3, 4, 14). Test sets with immobilized indicator micro-organisms, which can be prepared in laboratories or purchased, should be placed at re
47、levant places inside the equipment. The appropriate places for indicator micro-organisms should be identified either by suitable test methods or by risk assessment, Hazard Analysis Critical Control Points (HACCP) or Hazard and Operability studies (HAZOP). An example of a microbial challenge test met
48、hod is given in annex C 7. 3.6 Indirect test methods Indirect test methods can be applied when direct test methods are not available or inappropriate. They can be validated by a direct test method with respect to two dominating physical and/or chemical parameters which are time of treatment and the
49、required temperature or dose. These two parameters should be monitored inside a defined unit(s) of equipment at the places which are identified to show the worst sterilization conditions either by direct test methods or risk analysis. 4 Documentation The equipment manufacturer/supplier and/or the user should establish and document the testing procedure(s) used for the assessment of the sterilizability of the component or unit of equipment. This documentation should include the applied test conditions (test m
