1、| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | BRITISH STANDARD BS EN 12460:1998 The Euro
2、pean Standard EN 12460:1998 has the status of a British Standard ICS 07.080 NO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAW Biotechnology Large-scale process and production Guidance on equipment selection and installation in accordance with the biological riskThis British Stan
3、dard, having been prepared under the direction of the Sector Board for Materials and Chemicals, was published under the authority of the Standards Board and comes into effect on 15 July 1998 BSI 1998 ISBN 0 580 29844 2 BS EN 12460:1998 Amendments issued since publication Amd. No. Date Text affected
4、National foreword This British Standard is the English language version of EN 12460:1998. 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 com
5、mittee any enquiries on the interpretation, or 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-ref
6、erences The British Standards which implement international 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 Cat
7、alogue. A British Standard does not purport to 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 co
8、mprises a front cover, an inside front cover, the EN title page, pages 2 to 7 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
9、in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN 12460:1998 E EUROPEAN STANDARD EN 12460 NORME EUROPE ENNE EUROPA ISCHE NORM February 1998 ICS 07.080 Descriptors: Biotechnology, work safety, classifications, hazards, microorganisms, transgenic organisms, contamin
10、ation, accident prevention, environmental protection, laboratory equipment, containment enclosures English version Biotechnology Large-scale process and production Guidance on equipment selection and installation in accordance with the biological risk Biotechnologie Proce de a grande e chelle et pro
11、duction Guide pour la se lection et linstallation des e quipements en fonction du risque biologique Biotechnik Verfahren in Gromastab und Produktion Leitfaden zur Auswahl und Installation von Gera ten und Ausru stungen entsprechend dem biologischen Risiko This European Standard was approved by CEN o
12、n 31 January 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 without any alteration. Up-to-date lists and bibliographical references concerning such national standards m
13、ay 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 language made by translation under the responsibility of a CEN member into its own language and notified to the Ce
14、ntral 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, Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and United King
15、dom.Page 2 EN 12460:1998 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 Standard shall be given the status of a national standard, either by publication of an identical text or by e
16、ndorsement, at the latest by August 1998, and conflicting national standards shall be withdrawn at the latest by August 1998. According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following countries are bound to implement this European Standard: Austria, Bel
17、gium, Czech Republic, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom. Contents Page Foreword 2 1 Scope 3 2 Definitions 3 3 Procedure for selection of equipment 4 4 Verification of perfor
18、mance in practice 5 5 Control 5 6 Documentation 5 Annex A (informative) Examples of a risk analysis 6 Annex B (informative) Bibliography 6Page 3 EN 12460:1998 BSI 1998 1 Scope This European Standard gives guidance on the selection and risk analysis of biotechnological equipment and the subsequent as
19、sembly of this into a plant in order to attain the appropriate biosafety containment levels. This includes verification of installation, operation and maintenance. It also applies when a new process or significant changes are introduced into an existing plant. This European Standard applies if the b
20、iotechnological process includes the use of hazardous or potentially hazardous microorganisms and/or if the emission of such microorganisms into the working place and/or environment are restricted. However, this should be considered only as a part of the total safety approach required. Attention is
21、drawn to relevant European and national regulations. 2 Definitions For the purposes of this standard, the following definitions apply. 2.1 ancillary unit of equipment unit of equipment that is not in direct contact with the product, but which is nevertheless necessary to perform a process NOTE Examp
22、les of ancillary units of equipment are solvent recovery units for re-use of solvents, cleaning-in-place (CIP) units for preparation and storage of cleaning solutions. 2.2 component of equipment technical entity which forms part of a unit of equipment NOTE Examples of components of equipment are ves
23、sels, valves and sensors. 2.3 hazard intrinsic potential property or ability of something (e.g. any agent, equipment, material or process) to cause harm EN 1620 NOTE Harm is an injury or damage to health of people and/or to the environment. 2.4 microorganism any microbiological entity, cellular or n
24、on-cellular, capable of replication or of transferring genetic material EN 1619 NOTE For the purpose of this standard, the term microorganism covers the term of biological agent, according to the Directive 90/679/EEC: microorganisms, including those which have been genetically modified, cell culture
25、s and human endoparasites, which may be able to provoke any infection, allergy or toxicity. 2.5 physical containment system for confining a microorganism or organism or other entity within a defined space EN 1620 2.6 primary physical containment system of physical containment which limits the escape
26、 of a microorganism or organism into the working environment NOTE This can involve the use of closed containers or appropriate equipment, together with secure operating procedures. 2.7 process combination of unit operations for the production of a defined product and waste 2.8 process equipment unit
27、 of equipment which is in direct contact with the product NOTE Examples of process equipment are bioreactors, filters and separators. 2.9 process microorganism microorganism used for production purposes in a biotechnological process or constituting (part of) the product itself 2.10 process step indi
28、vidual defined part of the process which performs a specific function NOTE One combination of unit operations constitutes a process step. For example, downstream process could consist of separation, extraction, concentration and drying. 2.11 risk probability of occurrence of a hazard causing harm an
29、d the degree of severity of the harm 2.12 secondary physical containment system of physical containment which limits the escape of a microorganism or organism into the environment or into other working areas NOTE This can involve the use of rooms with specially designed air handling, the existence o
30、f airlocks and/or sterilizers for the removal of materials, and secure operating procedures. In many cases it can add to the effectiveness of primary physical containment. 2.13 unit of equipment assembly of components used to perform one or more unit operations 2.14 unit operation operation to perfo
31、rm a single chemical, physical or mechanical activity NOTE Examples of unit operation are heat transfer, mixing, separation (including filtration and centrifugation) and sterilization. 2.15 utilities units of equipment which supply energy and media NOTE Examples of utilities are units of equipment t
32、o generate and supply steam and pressurized air.Page 4 EN 12460:1998 BSI 1998 3 Procedure for selection of equipment 3.1 General approach In order to achieve a safe process through a selection of the appropriate equipment, it is necessary to define the process microorganism and the product, the proc
33、ess itself and the equipment proposed. An initial risk analysis should be carried out in order to determine the appropriate performance criteria of the proposed equipment. Based on this initial risk analysis, a detailed design should be carried out and equipment selected. This should be followed by
34、a detailed risk analysis, based on the specifications of equipment selected and its anticipated assembly into a plant. After the plant is assembled, verification should be carried out with respect to installation, operation and maintenance. Any subsequent changes in microorganism, process and/or equ
35、ipment should lead to a repeat of the initial risk analysis as a minimum. NOTE An example of how to perform such a risk analysis is given in annex A. 3.2 Microorganism(s) The microorganism(s) used in the process should be classified in accordance with its hazards. National and European rules of clas
36、sification should be followed (see annex B 1 and 2). NOTE Consideration should be given not only to pathogenicity, but also to the other biological hazards such as allergenicity, irritation, toxicity or harm to the environment. 3.3 Process and equipment description A fully written process descriptio
37、n should be prepared with all process steps listed and their relationships defined. NOTE 1 Flow sheets and/or block diagrams may be used as part of a detailed process description. The process equipment should be listed along with any ancillary units of equipment and utilities. This list facilitates
38、the evaluation of the process with respect to hazard and risk. NOTE 2 For each process step (e.g. downstream process) there are a number of unit operations (e.g. separation, extraction, concentration) which require process equipment (e.g. centrifuge, filter, homogenizer) assembled from components (e
39、.g. vessel, membrane support, valves, sensor). NOTE 3 It is possible for a piece of process equipment to be used for more than one process step, potentially involving different unit operations; e.g. a fermenter vessel can be used for fermentation (fermentation process step) or as a kill tank (downst
40、ream process step). 3.4 Initial risk analysis An initial risk analysis should be made of the draft process and equipment description as generated under 3.3. This analysis should be made with regard to the biological hazards, the probability of emission of microorganisms from the equipment and the po
41、tential routes of exposure of workers and of the environment, in accordance with national regulations. NOTE 1 Chemical or physical hazards should be identified and considered alongside the biological hazards, to ensure that the overall risks are not increased: for example, using disinfectant to kill
42、 microorganisms where the use of disinfectant is more of a risk than the living microorganisms. The objective of the risk analysis is to ensure the selection of and installation of the necessary process equipment in order to remove or reduce as far as possible the identified risks while still achiev
43、ing the main objective of making a product. The depth and/or detail of the risk analysis will depend on a number of factors, such as: the type and/or magnitude of hazards involved; the history and/or experience of the industry; the practical evidence of safe use of the components and process equipme
44、nt; the tradition or novelty of the process. NOTE 2 A suggested approach to the hazard or risk evaluation is to use established techniques such as HAZOP (see annex B 3, 4) and HACCP (see annex B 5, 6, 7), which are used in the chemical and food industries respectively, or other approaches of risk as
45、sessment (see annex B 8). The containment measures required to reduce the risk and to select the type of process equipment should be determined. The risk at each process step should then be assessed by examining the probability of emission from the equipment, and the exposure of workers and the envi
46、ronment to the microorganism(s). NOTE 3 In order to attain the required protection of the workers and the environment, containment measures to be applied could be, for example: for a negligible risk, good occupational safety and hygiene (GOSH) practice (see annex B 9); for a low risk, GOSH plus the
47、requirement to minimize release; for a medium risk, GOSH plus the prevention of release; or for a high risk, special requirements on a case-by-case analysis. 3.5 Detailed design of plant A detailed design of the proposed plant should be drawn up covering the selection and assembly of equipment, whic
48、h should comply with the assessed containment requirements. NOTE 1 The performance criteria for classification of units of equipment and components such as centrifuges, cell disrupters, bioreactors, tubes or couplings, with regard to cleanability, sterilizability and leaktightness are defined in ind
49、ividual equipment European Standards. NOTE 2 Guidance on testing procedures for cleanability, sterilizability and leaktightness are given in EN 12296, EN 12297 and EN 12298 (see annex B 10, 11, 12).Page 5 EN 12460:1998 BSI 1998 After selection of the appropriate equipment for specific process steps, attention should be paid to the assembly of equipment into a plant, including layout, couplings and piping. NOTE 3 The preferred way to realize an appropriate biosafety level is by means of
