EN 12460-1998 en Biotechnology - Large-Scale Process and Production - Guidance on Equipment Selection and Installation in Accordance with the Biological Risk《生物技术 大比例工艺法和生产 与生物危险性相.pdf

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1、STD-BSI BS EN L2LibO-ENGL L778 m Lb24bb7 0730587 4T4 m BRITISH STANDARD Biotechnology - Large-scale process and production - Guidance on equipment selection and installation in accordance with the biological risk The European Standard EN 124601998 has the status of a British Standard ICs 07.080 NO C

2、OPYING WITHOJT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGW LAW BS EN 124W.1998 STD-BSI BS EN 324bO-ENGL 3978 lb2Libb7 0730588 330 W BS EN 124601998 direction of the Sector Board for Materiais and Chemicals, was published under the authority of the Standards Board and comes into effect on 15 July

3、1998 hd. NO. National foreword Date Text afected This British Standard is the English language version of EN 12460.1998. The UK participation in its preparation was entrusted to Technical Committee CM8, Biotechnology, which has the responsibility to: - aid enquirers to understand the text; - present

4、 to the responsible European committee any enquines 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 re

5、quest to its secretary. Cross-references 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

6、 the BSI Standards Electronic Catalogue. A British Standard does not purport to include all the necessary provisions of a conhct. Users of British Standards are responsible for their correct application. Compliance with a British Standard does not of itself confer immunity from legal obligations. Su

7、mmary of pages This document comprises a front cover, an Wide e.g. a fermenter vessel can be used for fermentation (fermentation process step) or as a kdl tank (downstream process step). 3.4 Initial risk analysis An initial risk analysis should be made of the draft. process and equipment description

8、 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 potential routes of exposure of workers and of the environment, in accordance with nationai regulations. NOTE 1 considered alongside t

9、he biological hazards, to ensure that the overaii risks are not increased for example, using disinfectant to kill microorganisms where the use of disinfectant is more of a risk than the iiving microorganisms. The objective of the risk analysis is to ensure the selection of and installation of the ne

10、cessary process equipment in order to remove or reduce as far as possible the identifed risks while still achieving 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

11、 history andor experience of the industry; - the practical evidence of safe use of the components and process equipment; - the tradition or novelty of the process. Chemical or physical hazards should be identified and NOTE 2 A suggested approach to the hazard or risk evaluation is to use established

12、 techniques such as MOP (see annex B 3, 4) and HACCP (see annex B 5, 6, 7), which are used in the chemical and food indusbies respectively, or other approaches of risk assessment (see annex B 8). The containment measures required to reduce the risk and to select the type of process equipment should

13、be determined. The risk at each process step should then be assessed by examining the probabiliQ of emission from the equipment, and the exposure of workers and the environment to the microorganism(s). NOTE 3 In order to attain the required protection of the workers and the environment, containment

14、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 requirement to minimize release; - for a medium risk, GOSH plus the prevention of release; or - for a high risk, special requir

15、ements on a case-by-case analysis. 3.6 Detailed design of plant A detailed design of the proposed plant should be drawn up covering the selection and assembly of equipment, which should comply with the assessed containment requirements. NOTE 1 The performance criteria for classification of units of

16、equipment and components such as centrifuges, ceil disrupters, bioreactors, tubes or couplings, with regard to cleanability, stenlizability and leaktightness are defined in individual equipment European Standards. NOTE 2 Guidance on testing procedures for cleanability, sterilizability and leaktightn

17、ess are given in EN 12296, EN 12297 and EN 12298 (see annex B lo, li, 12). O BSI 1998 STD*BSI BS EN LZLibO-ENGL 1398 m Lb24bb7 0730573 7TB m Page 5 EN 12460:1998 After selection of the appropriate equipment for specific process steps, attention should be paid to the assembly of equipment into a plan

18、t, including layout, couplings and piping. NOTE 3 The preferred way to realize an appropriate biosafety level is by means of primary physical containment. However, if the desired biosafety level cannot be met, secondary physical containment should be used in addition. NOTE 4 To ensure the correct se

19、lection and adequate assembly of equipment, detailed twe and three-dimensional representation as necessary is recommended. In the process of selecting and assembling equipment, consideration should be given to risk associated with maintenance activities and the consequences of the equipment failure.

20、 3.6 Detailed risk analysis Based on an anticipated assembly of equipment into a piant, a detailed risk analysis should be made. The detailed risk analysis requires each of these components to be examined for each unit operation it is involved in, for example a valve (component) in a fermenter (proc

21、ess equipment) is required to operate during sterilization (unit operation) feeding medium (unit operation) and agitation (unit operation). During each of these unit operations the risk should be assessed If the risk is stiil unacceptable, the design of process step andor the microorganism in use sh

22、ould be reconsidered. 4 Verincation of performance in practice Conformance of the selected and assembled equipment with the assessed contallunent requirements should be verified after installation, during operation and with respect to maintenance. If the verification identifies nonconformance to the

23、 biosafety containment measures required, one or more steps should be reconsidered. 5 Control “here should be documented procedures to ensure that any changes in microorganism, equipment, processes or procedures subsequent to the above steps (see 3.4 to 3.6) should lead at least to a repeat of the i

24、nitiai risk analysis. If this analysis indicates that the desired containment level can no longer be met, further work, up to and including redesign, may be necessary to stay within safe limits. Records should be kept of results. 6 Documentation The risk analysis should be documented by the user alo

25、ng with the reasoning for equipment selection and assembly, and the results of the verification should demonstrate conformance with the requirements of this standard. * * rn O BSI 1998 STD-BSI BS EN 22qbU-ENGL 5998 m Lb24bb7 073059q b34 m Page 6 EN 1246&1998 Emission or Exposure Annex A (informative

26、) Examples of a risk analysis The risk analysis can be qualified simply by using the terms “negligible“, “low“, “medium“ and “high“ in relation to the hazard, the emission from the equipment, and the exposure of workers and the environment. in terms of the microorganism, category 1 is a negligible h

27、azard, category 2 is a low hazard, category 3 is a medium hazard and category 4 is a high hazard. in tem of the exposure, negligible exposure would occur where no contact is likely, for example in a static or remote system, low and medium exposure where there is a reasonable likelihood of exposure,

28、for example in an open sampling, and high exposure is where there is a definite contact, for example where an aerosol is generated or the process step is performed in the open air. The two factors are combined to give a risk analysis (see Fgure Al). For example, if there is a high emission from the

29、equipment or exposure to a low-hazard microorganism, the risk is medium. This risk score can then be translated into the containment principle required for the equipment to be used in each process step. NOTE An example of how the risk level can be calculated is given in the following matrix. N L M H

30、 A. Hazard B: Exposure C: Risk (combination of A and B) Negligible: category 1 Negligible: improbable contact N: Negligible LOW: category 2 Low possible contact L LOW Medium: category 3 Medium: probable contact M Medium High: category 4 High: defite contact H High I Hazard I Risk I II IM IM IH (H M

31、IL IL IM 1H IL IN IL IL IM I Annex B (informative) Bibliography 131 141 71 Pl 191 Council Directive 90/219/EEC of 23 April 1990 on the contained use of genetically modified microorganisms. OJEC 08.05.1990, no. L 117, p 1. Council Directive 90/679/EEC of 26 November 1990 on the protection of workers

32、from risks related to exposure to biological agents at work (seventh individual Directive within the meaning of Article 16 of Directive 89139llEEC). OJEC 31.12.1990, no. L 374, p 1. MAYES, T and KLISBY, D. (1989). The use of HAZOP hazard analysis to identify critical control points for the microbiol

33、ogical safety of food. Food Quality and Preference 1: 5357. KLETZ, T. (1992). HAZOP and HAZAN Identifying and Assessing Frocess Industry Hazards. 3rd edition. London institute of Chemical Engineers. ISBN O 85295 285 6. BRYAN, EL. Hazard Analysis Critical Control Point: What the System ZS and What it

34、 .is not. Journal of Environmentai Health, July/August 1988. Microorganism in Foods 4. Application of the Hazard Analysis Critical Control Point (HACCP). System to ensure m2crobiological safety and qualitg International Commission on Microbiological Specifications for Food (ICMSF). 1988. MAYES, T (1

35、992). Simple usersgui& to ULe hard analysis critica.! control point concept for the control of food microbiological safety. Food Control, 3(1): 1419. EN 1050, Safety of muchinmy - Principh for risk asses57rlnt. FROMMER, W. et al. (1993). Safe irotechnology (5). Recmmendutions for safe work with anim

36、al and human ceU cultures concerning potential human pathogens. Appl. Microbiol. BiotechnoL, 39 141-148. Guidance on testing procedures for cleanabilitg Guidance on testing proceaureS for sterilizabil.itg Guidance on testing procedum for leaktightness. EN 1619, Biotechnoogy - Large-scale p?vcess and

37、 pmductwn - Geneml requirements for managrnt and organization for strain conservation procedures. EN 1620, Biotechnology - Large-scale p?vcess and production - Plant buding according to the dem of hazard. EN 12296, Biotechnologrl- EqUiwt - EN 12297, Biotschnology - Equipment - EN 12298, Biohhmbgy -

38、Equi-t - O BSI 1998 STD-BSI BS EN 124bO-ENGL 1998 m lb24bb9 0710545 570 m Page 7 EN 12460:1998 PSIoN Containment I measures Low I Negligible i“*“/ High RISK I NO NO 1 YES In study V InstaIlatiodOperationMaintenance Figure A.l - Example of a risk analysis approach for selection of equipment according

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