1、12307 : 1998 Biotechnology - Large-scale process and production - Guidance for good practice, procedures, training and control for personnel The European Standard EN 12307 : 1997 has the status of a British Standard ICs 07.080; 07.100.99 NO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYR
2、IGHT LAW BS EN 12307 : 1998 National foreword This British Standard is the English language version of EN 12307 : 1997. The UK participation in its preparation was entrusted to Technical Committee CIv58, Biotechnology, which has the responsibility to: - aid enquirem to understand the text; - present
3、 to the responsible European committee any enquiries on the interpretation, or proposais for change, and keep the UK interests informed; - monitor related intedonai and European developments and promulgate them in the UK. A list of organizations represented on this committee can be obtained on reque
4、st to its secretary. Cross-references The British Standards which implement intrnational or European pubiications 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
5、 Standards Electronic Catalogue. A British Standard does not purport to include ail the necessary provisions of a conirad. 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 o
6、f pages This document comprises a hnt cover, an inside front cover, the EN title page, pages 2 to 6, an inside back cover and a back cover. This British Standard, having been prepared under the direction of the Sector Board for Materiais and Chemicals, was published under the authority of the Standa
7、rds Board and comes into effect on 15 March 1998 Amendments issued since publication ID* (Paaffected Amd No. O BSI 1998 ISBN O 680 29261 4 EUROPEAN sTANDAR;D NO- EUROPENNE EXJROP- NORM EN 12307 October 1997 ICs 07.080 07.100.99 Descriptors: Biotechnology, good laboratory practices, work safety, acci
8、dent prevention, environmental protection, hazards, contamination, micro-organisms, noxious micro-organisms, classifications, personnel, training, specifications Engush version Biotechnology - Laqpscale proces and production- for pemnnel Guidance for good practice, procedures, trainin$ and control B
9、iotechnologie - Procd grande chelle et production - Guide de bonnes practiques, procdures, formation et contrle pour le personnel Biotechnik - Verfahren im Grol3maBstab und Produktion - Leitfaden fur gute Praxis, Arbeitsablufe, Ausbildung und berwachung des Personals This European Standard was appro
10、ved by CEN on 21 August 1997. CEN members are bound to comply with the CENKENELEC 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 s
11、tandards 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 language made by translation under the responsibility of a CEN member into its own language and notifed
12、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, Rance, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and Uni
13、ted Kingdom. European Committee for Standardization Comit Europen de Normalisation Europisches Komitee fr Normung Central Secretariat: rue de Stassart 36, B-1050 Brussels O 1997 CEN AU rights of exploitation in any form and by any means reserved worldwide for CEN national Members Ref. No. EN 12307 :
14、 1997 E Page 2 EN 12307 : 1997 Foreword This European Standard has been prepared by “bchnical Committee CENR% 233, Biotechnoloa, 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 endors
15、ement, at the latest by Apri 1998, and conflicting national standards shall be withdrawn at the latest by Aprii 1998. This European Standard has been prepared under a mandate given to CEN by the European Commission and the European Free kade Association, and supports essential requirements of EU Dir
16、ective(s). Users of this European Standard, prepared in the field of application of article 118A of the EC treaty, should be aware that standards have no formai legal relationship with directives which may have been made under article 118A of the treaty In addition, national legislation in the membe
17、r states may contain more stringent requirements than the minimum requirements of a directive based on article 11 and - personal protective equipment which requirements are given in EN 143, EN 166, EN 3741 and EN 374-3. 2 Normative references This European Standard incorporates by dated or undated r
18、eference, provisions from other publications. These normative references axe cited at the appropriate places in the text and the publications are listed hereafter. For dated references, subsequent amendments to or revisions of any of these publications apply to this European Standard ony when incorp
19、orated in it by amendment or revision. For undated references the latest edition of the publication referred to applies. EN 143 Respiratmy protective dewices - Particle filters - Requirements, testing, marking Personal eye protectwn - Spei5fixation.s Protective gimes against chemicals and micro-orga
20、nisms - Part 1 : Tminology and perfomza,nce requirements EN 166 EN 3741 Page 3 EN 12307 : 1997 EN 374-3 Frotmtive gloves against chernicals and micro-organisms - Part 3 : Determination of resistance to permeatwn by chemicals Worlcpace atmospheres - Guidance for the assessment of exposure by inhalati
21、on to chemical agents for comparison wih limit values and measurement stmtegy Biotechnology - Large-scale process and pmduction - GmJ requirements for rna,rmgernent and organization for strain consmyation procedures Biotmhrwlogy - Large scale process and productwn - Plant building accoding to the de
22、gree of hazard EN 689 EN 1619 EN 1620 3 Definitions For the purposes of this standard, the following definitions apply: 3.1 controlled area Area constructed and/or operated in such a manner as to limit contamination of the other areas by micro-organismslorganisms from within the controlled area EN 1
23、6201. 3.2 hazard Inlxinsic potential property or abiiity of something (e.g. any agent, equipment, material or process) to cause harm EN 16201. NOTE. Harm is an injury or damage to health of people andor to the environment. 3.3 micro-organism Any microbiological enti, cellular or non-cellular, capabl
24、e of replication or of transferring genetic material EN 16191. 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
25、endoparasites, which may be able to provoke any infection, allergy or toxicity. 3.4 risk Probability of occurrence of a hazard causing hami and the degree of severity of the harm. 3.6 workplace The workplace is the dened area or areas in which the work activities are carried out EN 6891. 4 General c
26、onsiderations Before handling, micro-organisms should be classified with respect to human health and safety and hazard to the environment, according to national, European (see annex A i and 2) or intemational rules of classification. They should be handled in appropriate plant buildings of containme
27、nt levels 1,2,3 or 4 as indicated by an assessment of risk. Plant building should be designed in accordance with EN 1620. O BSI 1998 Page 4 EN 12307 : 1997 For any activity involving micro-organisms in large scale process and production activities, the principles of Good Occupaiionai Safety and Hygi
28、ene (GOSH) (see annex A 5) Good Microbiological khniques (see annex A 9), and Good Industrial Large Scale Practice (GILSP) (see annex A 6) should apply The basic recommendations for good microbiological practice are given in 6.1. Additional recommendations may be necessary in case of activities with
29、 potentially harmful microorganisms. Where appropriate, these additional recommendations are given in 6.2, 6.3 and 6.4. When micro-organisms are strictly pathogenic for plants and animals, specific recommendations aiming to limit or prevent their release intn the environment via the workers, can be
30、implemented on a case by case basis. It is emphasized that good microbiological practices are fundamental to safety and cannot generally be replaced by specialized equipment which can oniy supplement it partly NOTE. In this European Standard, the term good microbiological practice is used throughout
31、. The term good manufacturing practices (see annex A 7) relates mainly to the pharmaceutical industries and is not referred to in this document. 5 Recommendations for handling micro-organsms in large scale process and production activities 6.1 Basic recommendations for good microbiological practice
32、The following should be observed for handling all types of micro-organisms: a) workplace and environmental exposure to micro-organisms should be kept as low as reasonably practicable; b) animais not involved in the work should not be permitted in or near the workplace; c) the workplace should be kep
33、t neat, clean and free of materials that are not pertinent to the work; d) pipetting by mouth should be prohibiM, materials should not be placed in the mouth; e) all technical procedures should be performed in a way that minimizes the uncontained formation of aerosols and droplets; f) control method
34、s should be set up with engineering at source and these should be supplemented with appropriate personal protective equipment where necessary; g) control measures should be carried out and equipment should be tested and maintained; h) eating, drinking, smolang, storing of food and applying cosmetics
35、 should not be permitted in any area where infectious materiah are handid, i) workers should be provided with appropriate and adequate washing and toilet facilities; j) hans should be washed before leaving the workplace; k) workers should be provided with suitable work clothing and if necessary, add
36、itional personal protective equipment; 1) local rules for the safety and hygiene of personnel should be formulated and implemented; m) adequate written instructions should be available to keep exposure to any micro-organism to the lowest level that is reasonably practicable; n) training of personnel
37、 should be provided and recorded (see clause 6). 6.2 Additional recommendations for handling micro-organisms in a containment level 2 The following should be observed in addition to 6.1 for handling micro-organisms in pht building of containment level 2 : a) access to the workplace should be limited
38、 to nominated personnel; b) whilst work is in progress access to the controlled area should be restricted and clearly indicated. Entry points to the area (e.g. doors and windows) should be closed; c) in the event of spiliage, the contamhated areas should be disinfected by validated procedures; d) al
39、l materials (liquid, solid and gas) should be made safe by vaiidated means before leaving the controlled area; e) material, equipment and work clothing awaiting decontamination should be stored and transported in a safe manner in robust leakproof containers; f) workplaces and equipment should be mad
40、e safe prior to maintenance work. A system of formal authorization such as permit-to-work, should be instituted for maintenance personnel; g) effective disinfectants should be available for routine disinfection; h) hands should be immediately disinfected and then washed when contamination is suspect
41、ed, after handling infectious materiais and also before leaving the workplace; i) workers should immediately report any accident or incident to the person in charge or to the person responsible for safety and health at work; j) work clothing should not be stored in the same lockers or cupboard as st
42、reet clothing; k) work clothing should not be worn in areas such as offices, libraries, staff rooms and canteens; 1) medical surveillance should be provided in accordance with national laws and practices; m) appropriate personal protective equipment, for example gloves, safety glasses, face shields
43、(visors), should be provided and worn at the workplace when necessary; n) maintenance personnel should receive appropriate trainhg and jnstructions; o) staff should be adequately trained in emergency procedures to be applied in the event of an incident or accident These procedures should include det
44、ails of first aid, cleaning and disinfection. , O BSI 1998 STD-BSI BS EN 12307-ENGL 1998 1b24bb9 Ob87891 231 6.3 Additional recommendations for handling micro-organisms in a containment level 3 The following should be observed in addition to 6.1 and 6.2 for handling microorganisms in plant building
45、of containment level 3 a) access should be restricted to authorized workers; NOTE 1. This access should be made oniy through the airlock, if provided (see EN 1620). b) it is recommended that, at all times, a second competent person should be available to assist in the case of an emergency; NOTE 2. A
46、n observation window, or suitable alternative (e.g. closed circuit T.V.), should be installed in the workplace so that the occupants can be seen. c) an emergency plan with details of first aid accident procedures, isiiection and cleaning should be available, and staff should be trained accordingly;
47、safe procedures should be established for re-entering workplace; d) safe procedures should be established for fumigation and for re-entering workplace following fumigation; NOTE 3. The dunk tank should be sealed during fumigation if the disinfectant is incompatible with the fumigant. e) ali material
48、s and equipment should be made safe before being removed from the controlled area Removal of materials and equipment is undertaken only with authorization of the biosafety officer and under conditions defined in the local rules; NOTE 4. For example a doubleended dunk tank filled with an effective di
49、sinfectant or an alternative safe system, may be required for the removal of materials and equipment which cannot be autoclaved. NOTE 5. A procedure for transporation of living material should be provided under the control of the national authorities. f) personnel should shower before leaving the controlled area, where appropriate; g) where appropriate, a suitable, effective insect and rodent control programme should be instituted; h) all technical procedures should be performed in a way that prevents the uncontained formation of aerosols and dro
