1、| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | BRITISH STANDARD BS EN 12685:1998 The Euro
2、pean Standard EN 12685:1998 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 Modified organisms for application in the environment Guidance for the monitoring strategies for deliberate release of genetical
3、ly modified micro-organisms, including virusesBS EN 12683:1998 This British Standard, having been prepared under the direction of the Sector Committee for Materials and Chemicals, was published under the authority of the Standards Committee and comes into effect on 15 December 1998 BSI 1998 ISBN 0 5
4、80 30178 8 Amendments issued since publication Amd. No. Date Text affected National foreword This British Standard is the English language version of EN 12685:1998. The UK participation in its preparation was entrusted to Technical Committee CII/58, Biotechnology, which has the responsibility to: ai
5、d enquirers to understand the text; present to the responsible European committee 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 represent
6、ed on this committee can be obtained on request 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
7、Index”, or by using the “Find” facility of the BSI Standards Electronic Catalogue. 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 itsel
8、f confer immunity from legal obligations. Summary of pages This document comprises a front cover, an inside front cover, the EN title page, pages 2 to 10, an inside back cover and a back cover.CEN European Committee for Standardization Comite Europe en de Normalisation Europa isches Komitee fu r Nor
9、mung Central Secretariat: rue de Stassart 36, B-1050 Brussels 1998 CEN All rights of exploitation in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN 12685:1998 E EUROPEAN STANDARD EN 12685 NORME EUROPE ENNE EUROPA ISCHE NORM July 1998 ICS 07.080; 07.100.01 Descript
10、ors: biotechnology, genetics, modified organisms, environments, environmental protection, inspection, experimental design English version Biotechnology Modified organisms for application in the environment Guidance for the monitoring strategies for deliberate releases of genetically modified micro-o
11、rganisms, including viruses Biotechnologie Organismes modifie s disse mine s dans lenvironnement Guide des strate gies de surveillance pour les disse minations volontaires de micro-organismes ge ne tiquement modifie s, y compris de virus Biotechnik Vera nderte Organismen zum Einsatz in der Umwelt Le
12、itfaden fu r die U berwachungsstrategien bei der absichtlichen Freisetzung gentechnisch vera nderter Mikroorganismen einschlielich Viren This European Standard was approved by CEN on 1 July 1998. CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions
13、 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 may be obtained on application to the Central Secretariat or to any CEN member. This European Standard exists in three offic
14、ial 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 Central Secretariat has the same status as the official versions. CEN members are the national standards bodies of Austria, B
15、elgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and United Kingdom.Page 2 EN 12685:1998 BSI 1998 Foreword This European Standard has been prepared by Technical Committee CEN/TC 233, Biot
16、echnology, 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 endorsement, at the latest by January 1999, and conflicting national standards shall be withdrawn at the latest by January 1
17、999. This European Standard has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association. According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following countries are bound to implement this European Stand
18、ard: Austria, Belgium, 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 Introduction 3 1 Scope 3 2 Normative references 3 3 Definitions 3 4 Genera
19、l considerations 4 5 Monitoring strategy 4 Annex A (informative) Relationship between a sampling and monitoring valid strategy 9 Annex B (informative) Bibliography 10Page 3 EN 12685:1998 BSI 1998 Introduction When genetically modified micro-organisms including viruses (GMMs) are subject to experimen
20、tal release into the environment, it is important to ensure the validity of a monitoring strategy for testing their behaviour. In this European Standard, monitoring refers both to the monitoring of the occurrence, persistence and/or spread of the GMM and/or the gene(s) involved in the modification a
21、nd its performance in the environment. This European Standard is intended to aid the experimenter in the design of a monitoring strategy appropriate to monitoring objectives. The development of a monitoring valid strategy is directly linked to the development of the sampling strategy as described in
22、 EN 12686. Therefore, this European Standard gives the experimenter a list of points that should be considered in determining the validity of a monitoring strategy comprising valid design, review, execution and documentation of a monitoring protocol. 1 Scope This European Standard provides guidance
23、on factors and criteria considered for the determination of the suitability and validity of the design, development and execution of a monitoring strategy for GMM. Monitoring encompasses detection of genotypic and phenotypic properties, as well as detection of viral material and/or symptoms specific
24、 for the infected host, for the identification of GMMs in an experimental release. This European Standard provides the person conducting a monitoring programme with a list of factors and criteria that should be considered in determining the validity of the proposed strategy for monitoring. This Euro
25、pean Standard is specifically aimed at monitoring experimental release of GMMs or their nucleic acid. This European Standard however, does not cover: the monitoring of virus-like entities or similar agents; the monitoring of GMMs for food, human health and veterinary applications. NOTE Attention is
26、drawn to national, European and international regulations, and relevant standards covering the monitoring of GMMs in food, human health and veterinary applications. 2 Normative references This European Standard incorporates by dated or undated reference, provisions from other publications. These nor
27、mative 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 these publications apply to this European Standard only when incorporated in it by amendment or revision. For undated ref
28、erences the latest edition of the publication referred to applies. EN 12686, Biotechnology Modified organisms for application in the environment Guidance for the sampling strategies for deliberate releases of genetically modified micro-organisms, including viruses. 3 Definitions For the purposes of
29、this standard, the following definitions apply: 3.1 analyte substance sought or determined 3.2 behaviour interaction of the organism(s) with abiotic and biotic environments, its (their) occurrence, persistence, multiplication and spreading abilities 3.3 control preparation of known characteristics u
30、sed to standardize an analysis 3.4 detection recognition of the presence of an organism or of a molecular structure within a sample 3.5 genetic modification of interest conceptual design for altering the genetic material within an organism NOTE 1 The genetic modification of interest can be described
31、 at different levels of molecular detail. NOTE 2 The conceptual design can include insertion, substitution or deletion of genetic material. 3.6 genetically modified micro-organism micro-organism in which the genetic material has been altered in a way that does not occur naturally by mating and/or na
32、tural recombination NOTE Within the terms of this definition genetic modification occurs at least through the use of the techniques listed in the Directive 90/219/EEC or its appropriate annexes (see annex B 1). 3.7 genotype genetic constitution of an organism NOTE The genotype can be described with
33、respect to particular genes. 3.8 host target species for virus replication as defined in the experimental designPage 4 EN 12685:1998 BSI 1998 3.9 identification establishment of identity by comparison with a reference NOTE 1 The reference could be an organism, a molecular structure or the genetic mo
34、dification of interest. NOTE 2 The certainty of identification is affected by the types and/or number of characteristics investigated. 3.10 micro-environment defined location in the environment potentially occupied by an organism NOTE This “micro-environment” can impart a degree of confinement on th
35、e dispersal of the organism. 3.11 monitoring regular or continuous observation or collection of data with respect to an organism, process or procedure NOTE In this standard, monitoring applies to the progress of a released genetically modified organism. 3.12 monitoring protocol list of sequential st
36、eps and methods to be used for monitoring 3.13 monitoring strategy procedure for designing, reviewing, executing and documenting a monitoring protocol 3.14 phenotype sum of the traits of an organism NOTE 1 The phenotype can be described with respect to one or more traits under a given set of conditi
37、ons. NOTE 2 In the case of a virus, the phenotype can be described by one or more traits manifested in the infected host. 3.15 release site defined area which contains one or more experimental fields NOTE Several different trials can occur within a release site. 4 General considerations Monitoring i
38、s important in order to test predictions made with respect to the behaviour of the GMM in a release site. The availability and use of adequate controls is essential for the validity of the results. The design and execution of a monitoring valid strategy is therefore dependent on the particular objec
39、tives of the monitoring strategy. These can include the following. a) Studies on the functioning of the genetic modification in the GMM, released in the environment. The monitoring programme can include studies on the molecular stability and functional expression of the gene(s) involved in the genet
40、ic modification of interest. b) Studies on the effect of the genetic modification of interest on the behaviour of the GMM, released in the environment. The monitoring strategy can include studies on the presence of the GMM of interest or its hosts in environmental samples or its performance in the e
41、nvironment including effects on the ecosystem considered. c) Studies on the transfer of the gene(s) involved in the genetic modification of interest. The monitoring programme can include studies on transfer to the indigenous microbial population. 5 Monitoring strategy 5.1 General It is first necessa
42、ry to determine the objectives of the monitoring strategy. The main steps in the development of the monitoring strategy are: a) design and review of the monitoring protocol; b) validation of the monitoring protocol; c) execution of the monitoring protocol; d) record keeping. Responsibility for these
43、 steps should be assigned to a specific authority, organization or person. The monitoring strategy should be reviewed regularly, in the light of the inspections of the release site, to ensure its continuing validity. 5.2 Criteria for the design of the monitoring protocol The following key factors sh
44、ould be considered in the initial design of the protocol to ensure the design correlates with the monitoring strategy objectives as determined by the person designing the test: a) sampling strategy appropriate to the objectives and needs of the monitoring strategy as described in EN 12686; NOTE The
45、development of a monitoring and sampling valid strategy for deliberate releases of genetically modified micro-organisms in the environment is summarized in Figure A.1. b) extent of monitoring necessary to fulfil the requirements of the experiment such as timescale, scale and area of sampling; c) pre
46、dicted behaviour of GMM, particularly with respect to competitive ability, dispersal, persistence and the ability to form spores, resting forms and other specialized structures; d) relevant area for monitoring in line with the monitoring objectives such as the release site and/or the potential dispe
47、rsal area; e) particular features of the release site to monitor such as adjacent sites, streams, soil movement activities, meteorological parameters, soil properties; f) presence of potential hosts, presence of potential microbial vectors; g) appropriate choice of monitoring methods.Page 5 EN 12685
48、:1998 BSI 1998 5.3 Validity of the design of the monitoring protocol 5.3.1 General Factors and criteria which should be considered for the determination of the suitability and validity of a monitoring protocol are given in 5.3.2 to 5.3.5. The following lists of factors and criteria should not be con
49、sidered as exhaustive. 5.3.2 Considerations with respect to fulfilling the overall experimental objective In fulfilment of the overall experimental objective, the aim of individual experiments can be: detection; identification; determination of the molecular stability of the gene expression; determination of the effect of the modification; rapid screening or detailed investigation; quantitative or qualitative approach. 5.3.3 Considerations with respect to the genetic modification of interest The factor(
