BS EN 1619-1997 Biotechnology - Large-scale process and production - General requirements for management and organization for strain conservation procedures《生物技术 大规模加工和生产 应变保存程序管理和.pdf

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1、| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | BRITISH STANDARD BS EN 1619 : 1997 The Eur

2、opean Standard EN 1619 : 1996 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 General requirements for management and organization for strain conservation proceduresBS EN 1619 : 19

3、97 This British Standard, 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 January 1997 BSI 1997 The following BSI references relate to the work on this standard: Committee r

4、eference CII/58 Draft for comment 94/506353 DC ISBN 0 580 26771 7 Amendments issued since publication Amd. No. Date Text affected Committees responsible for this British Standard The preparation of this British Standard was entrusted to Technical Committee CII/58, Biotechnology, upon which the follo

5、wing bodies were represented: Association of Consultants to the Bioscience Industries (Acbi) BLWA Ltd. (The Association of the Laboratory Supply Industry) Bioindustry Association Brewing Research Foundation International British Agrochemicals Association Ltd. Chemical Industries Association Confeder

6、ation of British Industry Department of Health Department of the Environment (Air Climate and Toxic Directorate) Health and Safety Executive Institution of Chemical Engineers International Society for Pharmaceutical Engineering Ministry of Agriculuture, Fisheries and Food National Engineering Labora

7、tory Public Health Laboratory Service Society for Applied Bacteriology Society for General MicrobiologyBS EN 1619 : 1997 BSI 1997 i Contents Page Committees responsible Inside front cover National foreword ii Foreword 2 Introduction 3 Text of EN 1619 3ii BSI 1997 BS EN 1619 : 1997 National foreword

8、This British Standard has been prepared by CII/58 and is the English language version of EN 1619 Biotechnology Large-scale process and production General requirements for management and organization for strain conservation procedures, published by the European Committee for Standardization (CEN). EN

9、 1619 is the result of European discussion in which the UK took a full part. Compliance with a British Standard does not of itself confer immunity from legal obligations. This document comprises a front cover, an inside front cover, pages i and ii, pages 1 to 6, an inside back cover and a back cover

10、.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 1996 All rights of reproduction and communication in any form and by any means reserved in all countries to CEN and its members Re

11、f. No. EN 1619 : 1996 E EUROPEAN STANDARD EN 1619 NORME EUROPE ENNE EUROPA ISCHE NORM July 1996 ICS 07.100.00 Descriptors: biotechnology, reproduction (biology), culture (biology), micro-organisms, designation, preservation, hazards, management, organization, storage English version Biotechnology La

12、rge-scale process and production General requirements for management and organization for strain conservation procedures Biotechnologie Proce de a grande e chelle production Exigences ge ne rales de gestion et dorganisation pour les proce dures de conservation des souches Biotechnik Verfahren im Gro

13、mastab und Produktion Allgemeine Anforderungen an Verwaltung und Organisation bei Verfahren zur Stammkonservierung This European Standard was approved by CEN on 1996-05-02. CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this Europe

14、an Standard the status of a national standard 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,

15、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 Central Secretariat has the same status as the official versions. CEN members are the national standards bodies of Austria, Belgium, Denmark, Finlan

16、d, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and United Kingdom.Page 2 EN 1619 : 1996 BSI 1997 Foreword This European Standard has been prepared by Technical Committee CEN/TC 233, Biotechnology, the secretariat of which is

17、 held by AFNOR. This European Standard shall be given the status of a national standard, either by publication of an identical text or by endorsement, at the latest by January 1997, and conflicting national standards shall be withdrawn at the latest by January 1997. According to the CEN/CENELEC Inte

18、rnal Regulations, the national standards organizations of the following countries are bound to implement this European Standard: Austria, Belgium, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United

19、Kingdom. Contents Page Foreword 2 Introduction 3 1 Scope 3 2 Normative references 3 3 Definitions 3 4 Development of master and working cell banks 3 5 Classification of micro-organisms 4 6 Preservation 4 7 Characterization 4 8 Handling and storage 4 9 Personnel and facilites 4 Annexes A (informative

20、) Classification of the micro-organisms 5 B (informative) Bibliography 6Page 3 EN 1619 : 1996 BSI 1997 Introduction This European Standard covers a wide area of applications of biotechnology. This European Standard supports industrial activities in the area of biotechnology covering both natural mic

21、ro-organisms and genetically modified micro-organisms (GMMs), including both non-pathogenic and pathogenic micro-organisms (see annex B 1, 2). NOTE. Non-genetically modified micro-organisms include natural micro-organisms and micro-organisms improved by traditional techniques. In order to obtain rep

22、roducible results, cell banks (master cell bank and working cell bank) of micro-organisms chosen for production of a particular product are established. 1 Scope This European Standard specifies general requirements for management and organization of procedures for conservation of micro-organisms use

23、d for large-scale process and production. It is intended to secure safe handling and also to ensure that reproducible results are obtained in biotechnology processes. This European Standard specifies methods of handling and preservation of microbial strains or cell lines obtained from animals, plant

24、s and viruses in order to get reproducible and safe cultivation processes for the industrial production of substances. NOTE. Attention is drawn to the existing national regulations concerned with the handling of micro-organisms. This European Standard is applicable to micro-organisms. 2 Normative re

25、ferences This European Standard incorporates by dated or undated reference, provisions from other publications. These normative references are 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

26、these publications apply to this European Standard only when incorporated in it by amendment or revision. For undated references the latest edition of the publication referred to applies. prEN 12128 Biotechnology Laboratories for research, development and analysis Containment levels of microbiology

27、laboratories, areas of risk, localities and physical safety requirements 3 Definitions For the purposes of this standard, the following definitions apply: 3.1 characterization Description of a number of properties of micro-organisms according to EN 1619. 3.2 lyophilization Preservation by freezing a

28、nd dehydration under vacuum. 3.3 master cell bank (MCB) Stock of cells from which all subsequent cell banks are derived. NOTE 1. MCB stock is not normally intended for use directly in production. NOTE 2. The term MCB covers all type of cells, i.e. micro-organisms as defined in EN 1619. 3.4 micro-org

29、anism Any microbiological entity, cellular or non cellular, capable of replication or of transferring genetic material. NOTE. 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, cel

30、l cultures and human endoparasites which may be able to provoke any infection, allergy or toxicity. 3.5 pathogenicity Ability to cause disease. 3.6 probe; gene probe Specific nucleic acid sequence used to identify certain DNA or RNA fragments by means of hybridization. NOTE. The gene probe is labell

31、ed in a way that permits detection, e.g. by radioactivity. 3.7 stability Ability of micro-organisms to survive during storage while retaining initial characteristics such as expression of a marker or synthesis of a desired product. 3.8 working cell bank (WCB) Stocks of cells derived from the master

32、cell bank (MCB), which are used for inoculation. NOTE. The term WCB covers all type of cells, i.e. micro-organisms as defined in EN 1619. 4 Development of master and working cell banks When a production strain has been developed by natural selection, any type of mutation, or by genetic engineering,

33、a master cell bank (MCB) shall be established and shall be preserved by a defined or validated procedure (see clause 6). When the MCB has been established a working cell bank (WCB) shall be established. Before this is used in industrial production, it should be characterized with the appropriate deg

34、ree of scrutiny.Page 4 EN 1619 : 1996 BSI 1997 The stability of a micro-organism used in large-scale processes requires that the properties of this micro-organism with regard to safety and its production value are stable when preserved as MCB or WCB as well as when used under fermentation conditions

35、. In the latter case it should be shown not to change characteristics under prolonged normal fermentation conditions unless it is the normal life cycle of the micro-organism under the culture conditions used. NOTE. General quality standards such as EN ISO 9000 series (see annex B 4) may be used to e

36、nsure control of MCB and WCB quality. This should also ensure through adequate documentation that the control procedures are applied. 5 Classification of micro-organisms The micro-organism shall be classified according to its degree of hazard to people, animals, plants and/or the environment. This c

37、lassification shall be used in the risk assessment which determines the containment level required. NOTE 1. Annex A gives a common basis for classification. NOTE 2. European (see annex B 3) and/or national lists of classification should be a primary source of information. NOTE 3. Genetically modifie

38、d micro-organisms are assessed according to the criteria listed in the Directive 90/219/EEC, Annex III (see annex B 1). 6 Preservation A defined or validated method of preservation shall be adopted. NOTE 1. Depending on survival and stability, the cell bank can be preserved lyophilized or kept froze

39、n at -70 C or lower temperature (e.g. liquid nitrogen) in an appropriate medium. NOTE 2. A range of other procedures which may be also appropriate exist. 7 Characterization In order to identify the micro-organism, a wide range of procedures may be used to characterize it. The ones selected will depe

40、nd on the micro-organisms identity. NOTE 1. The following parameters should be determined where appropriate: a) history of the strain or cell-line, e.g. origin, source, when and where first characterized and taxonomic description, and whether modified; b) physical description, e.g. microscopic and c

41、olonial morphology, Gram reaction, motility, spore formation (present or not); c) physiological parameters, e.g. temperature (optimum), pH (optimum), aerobic, anaerobic and other gas atmosphere requirements; d) biochemical and molecular markers and/or properties tested by relevant available tests; e

42、) nutritional requirements: nitrogen, carbon, and other energy sources, growth factors, vitamins, minerals (if known); f) gene probes for specific factors; g) freedom from adventitious agents: cell lines should not contain unwanted viruses or mycoplasma; bacteria should not contain unwanted phages.

43、NOTE 2. Genetically modified micro-organisms should be further characterized with reference to gene elements inserted on plasmids or on the chromosome, according to relevant national, European or international regulations. 8 Handling and storage 8.1 Preparation of cell banks (MCB and WCB) a) micro-o

44、rganisms shall be stored in appropriate vials (tube, ampoule or flask); b) each vial shall be clearly identified and this shall enable the user as appropriate to determine the content, production date, expiration date and reference number and category. NOTE. In order to avoid accidental loss, all ce

45、ll banks should be stored in at least two different storage (freezing, etc.) units. These should, if possible, be located in separate rooms or buildings. The vials should be stored in containers inside the locked storage unit, which is accessible only to authorized individuals. c) micro-organisms sh

46、all be stored in containers or controlled areas appropriately designed for the containment level as indicated by risk assessment. If a secondary storage unit is used outside the required containers, this shall be in accordance with national and European regulations; d) instructions on the handling o

47、f accidental spillage or release from these containers shall be available at the site of the storage unit; e) the location, identity and inventory of individual vials of cells shall be documented; f) transportation shall be carried out according to the appropriate regulations. 8.2 Stability testing

48、of cell banks (MCB and WCB) It is recommended that: viability and other properties of cell banks should be tested regularly by viable counts or by other equivalent methods to ascertain stability during storage; properties of cell banks should be characterized periodically if relevant. 9 Personnel an

49、d facilities 9.1 Personnel Records shall be kept to demonstrate that personnel are adequately trained with regard to safe handling of the different categories of micro-organisms with which they work. NOTE. A standard Guidance for good practice for laboratory operations is being prepared (see annex B 6). 9.2 Facilities Facilities shall be designed and built in accordance with appropriate national and European regulations and prEN 12128, related to laboratory and production plant work. NOTE. Development and charac