1990L0219—EN—20.11.2003—004.001—1
This document is meant purely as a documentation tool and the institutions do not assume any liability for its contents
►B COUNCILDIRECTIVE
of23April1990
onthecontaineduseofgenetically modifiedmicro-organisms
(90/219/EEC)
(OJL117,8.5.1990,p.1)
Amendedby:
OfficialJournal
No page date
►M1CommissionDirective94/51/ECof7November1994 L297 29 18.11.1994
►M2CouncilDirective98/81/ECof26October1998 L330 13 5.12.1998
►M3CouncilDecision2001/204/ECof8March2001 L73 32 15.3.2001
►M4Regulation (EC) No 1882/2003 of the European Parliament and of the
Councilof29September2003L284 1 31.10.2003
Correctedby:
►C1Corrigendum,OJL93,8.4.1999,p.27(98/81/EC)
▼B
COUNCILDIRECTIVE
of23April1990
onthecontaineduseofgenetically modifiedmicro-organisms
(90/219/EEC)
THECOUNCILOFTHEEUROPEANCOMMUNITIES,
Having regard to the Treaty establishing the European Economic
Community,andinparticularArticle130sthereof,
HavingregardtotheproposalfromtheCommission(1),
HavingregardtotheopinionoftheEuropeanParliament(2),
Having regard to the opinion of the Economic and Social
Committee(3),
Whereas, under the Treaty, action by the Community relating to the
environmentshallbebasedontheprinciplethatpreventiveactionshallbe taken and shall have as its objective to preserve, protect andimprovetheenvironmentandtoprotecthumanhealth;
WhereastheCouncilResolutionof19October1987(
4)concerningthe
Fourth Environmental Action Programme of the European Commu-nitiesdeclaresthatmeasuresconcerningtheevaluationandbestuseofbiotechnology with regard to the environment are a priority area onwhichCommunityactionshouldconcentrate;
Whereas the development ofbiotechnology issuchasto contribute to
the economic expansion of the Member States; whereas this impliesthat genetically modified micro-organisms will be used in operationsofvarioustypesandscale;
Whereas the contained use of genetically modified micro-organisms
should be carried out in such way as to limit their possible negativeconsequences for human health and the environment, due attention
beinggiventothepreventionofaccidentsandthecontrolofwastes;
Whereas micro-organisms, if released in the environment in one
MemberStateinthecourseoftheircontaineduse,mayreproduceandspread,crossingnational frontiersandtherebyaffecting otherMember
States;
Whereas, in order to bring about the safe development of biotech-
nology throughout the Community, it is necessary to establishcommon measures for the evaluation and reduction of the potential
risks arising in the course of all operations involving the contained
use of genetically modified micro-organisms and to set appropriateconditionsofuse;
Whereas the precise nature and scale of risks associated with geneti-
cally modified micro-organisms are not yet fully known and the risk
involved must be assessed case by case; whereas, to evaluate risk forhumanhealthandtheenvironment,itisnecessarytolaydownrequire-mentsforriskassessment;
Whereas genetically modified micro-organisms should be classified in
relation to the risks they present; whereas criteria should be providedforthispurpose;whereasparticularattentionshouldbegiventoopera-tionsusingthemorehazardousgeneticallymodifiedmicro-organisms;
Whereas appropriate containment measures should be applied at the
variousstagesofanoperationtocontrolemissionsandtopreventacci-dents;1990L0219—EN—20.11.2003—004.001—2
(1) OJNoC198,28.7.1988,p.9and
OJNoC246,27.9.1989,p.6.
(2) OJNoC158,26.6.1989,p.122and
OJNoC96,17.4.1990.
(3) OJNoC23,30.1.1989,p.45.
(4) OJNoC328,7.12.1987,p.1.
▼B
Whereasanyperson,beforeundertakingforthefirsttimethecontained
use of a genetically modified micro-organism in a particular installa-tion, should forward to the competent authority a notification so that
the authority may satisfy itself that the proposed installation is appro-
priate to carry out the activity in a manner that does not present ahazardtohumanhealthandtheenvironment;
Whereasitisalsonecessarytoestablishappropriateproceduresforthe
case-by-casenotificationofspecificoperationsinvolvingthecontained
use of genetically modified micro-organisms, taking account of the
degreeofriskinvolved;
Whereas, in the case of operations involving high risk, the consent of
thecompetentauthorityshouldbegiven;
Whereasitmaybeconsideredappropriatetoconsultthepubliconthe
containeduseofgeneticallymodifiedmicro-organisms;
Whereas appropriate measures should be taken to inform any person
liabletobeaffectedbyanaccidentonallmattersrelatingtosafety;
Whereas emergency plans should be established to deal effectively
withaccidents;
Whereas,ifanaccidentoccurs,theusershouldimmediatelyinformthe
competent authority and communicate the information necessary forassessing the impact of that accident and for taking the appropriateaction;
WhereasitisappropriatefortheCommission,inconsultationwiththe
Member States, to establish a procedure for the exchange of informa-tion on accidents and for the Commission to set up a register of suchaccidents;
Whereas the contained use of genetically modified micro-organisms
throughout the Community should be monitored and to this end
MemberStatesshouldsupplycertaininformationtotheCommission;
Whereas a committee should be set up to assist the Commission on
mattersrelatingtotheimplementationofthisDirectiveandtoitsadap-tationtotechnicalprogress,
HASADOPTEDTHISDIRECTIVE:
Article 1
This Directive lays down common measures for the contained use of
geneticallymodifiedmicro-organismswithaviewtoprotectinghumanhealthandtheenvironment.
Article 2
ForthepurposesofthisDirective:(a) ‘micro-organism’ shall mean any microbiological entity, cellular
or non-cellular, capable of replication or of transferring geneticmaterial, including viruses, viroids, animal and plant cells in
culture;
(b) ‘genetically modified micro-organism’ (GMM) shall mean a
micro-organism in whichthe genetic material hasbeen altered in
a way that does not occur naturally by mating and/or natural
recombination.
Withinthetermsofthisdefinition:
(i) genetic modification occurs at least through the use of the
techniqueslistedinAnnexI,PartA;
(ii) thetechniqueslistedinAnnexI,PartB,arenotconsideredto
resultingeneticmodification;
(c) ‘containeduse’ shallmeananyactivityinwhichmicro-organisms
are genetically modified or in which such GMMs are cultured,stored, transported, destroyed, disposed of or used in any other1990L0219—EN—20.11.2003—004.001—3
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way, and for which specific containment measures are used
►C1to limit their contact with, and to provide a high level of
safetyfor,thegeneralpopulationandtheenvironment; ◄
(d) ‘accident’ shall mean any incident involving a significant and
unintended release ofGMMsinthecourseoftheircontained use
which could present an immediate or delayed hazard to humanhealthortheenvironment;
(e) ‘user’ shall mean any natural or legal person responsible for the
containeduseofGMMs;
(f) ‘notification’ shallmeanthepresentationoftherequisiteinforma-
tiontothecompetentauthoritiesofaMemberState.
Article 3
WithoutprejudicetoArticle5(1)thisDirectiveshallnotapply:
— wheregeneticmodificationisobtainedthroughtheuseofthetech-
niques/methodslistedinAnnexII,PartA,or
— for contained uses involving only types of GMMs meeting the
criteria listed in Annex II, Part B which establish their safety to
humanhealthandtheenvironment.ThesetypesofGMMsshallbelistedinAnnexII,PartC.
Article 4
Article5(3)and5(6)andArticles6to12shallnotapplytothetrans-
portofGMMsbyroad,rail,inlandwaterway,seaorair.
ThisDirectiveshallnotapplytothestorage,culture,transport,destruc-
tion,disposaloruseofGMMswhichhavebeenplaced onthemarketinaccordancewithCouncilDirective90/220/EECof23April1990onthe deliberate release into the environment of genetically modifiedorganisms(
1) or pursuant to other Community legislation, which
provides for a specific environmental risk assessment similar to that
laid down in the said Directive, provided that the contained use is in
accordance with the conditions, if any, of the consent for placing onthemarket.
Article 5
1. Member States shall ensure that all appropriate measures are
taken to avoid adverse effects on human health and the environmentwhichmightarisefromthecontaineduseofGMMs.
2. To this end the user shall carry out an assessment of the
contained uses as regards the risks to human health and the environ-ment that these contained uses may incur, using as a minimum theelementsofassessmentandtheproceduresetoutinAnnexIII,sectionsAandB.
3. Theassessmentreferredtoinparagraph2shallresultinthefinal
classification ofthecontained usesinfourclassesapplying theproce-dure set out in Annex III, which will result in the assignment ofcontainmentlevelsinaccordancewithArticle6:
Class1: activities ofnoornegligible risk,thatistosayactivities for
which level 1 containment is appropriate to protect humanhealthaswellastheenvironment.
Class2: activities oflowrisk,thatistosayactivities forwhichlevel
2containmentisappropriatetoprotecthumanhealthaswell
astheenvironment.
Class3: activities ofmoderate risk,thatistosayactivities forwhich
level3containmentisappropriatetoprotecthumanhealthaswellastheenvironment.1990L0219—EN—20.11.2003—004.001—4
(1) OJL117,8.5.1990,p.15.DirectiveaslastamendedbyCommissionDirec-
tive97/35/EC(OJL169,27.6.1997,p.72).
▼M2
Class4: activitiesofhighrisk,thatistosayactivitiesforwhichlevel
4containmentisappropriatetoprotecthumanhealthaswellastheenvironment.
4. Where there is doubt as to which class is appropriate for the
proposed contained use, the more stringent protective measures shallbeappliedunlesssufficientevidence,inagreementwiththecompetentauthority,justifiestheapplicationoflessstringentmeasures.
5. The assessment referred to in paragraph (2) shall especially take
into account the question of disposal of waste and effluents. Whereappropriate, the necessary safety measures shall be implemented inordertoprotecthumanhealthandtheenvironment.
6. A record of the assessment referred to in paragraph (2) shall be
kept by the user and made available in an appropriate form to thecompetent authority as part of the notification pursuant to Articles 7,9and10oronrequest.
Article 6
1. The user shall apply, except to the extent that paragraph 2 of
Annex IV allows other measures to be applied, the general principlesandthe appropriate containment and other protective measures setoutin AnnexIV corresponding to the class of the contained use, soas to
keep workplace and environmental exposure to any GMMs to the
lowest reasonably practicable level, and so that a high level of safetyisensured.
2. The assessment referred to in Article 5(2) and the containment
and other protective measures applied shall be reviewed periodically,
andforthwithif:
(a) the containment measures applied are no longer adequate or the
classassignedtothecontainedusesisnolongercorrect,or
(b) there is reason to suspect that the assessment is no longer appro-
priatejudgedinthelightofnewscientificortechnicalknowledge.
Article 7
Whenpremisesaretobeusedforthefirsttimeforcontaineduses,the
user shall be required to submit to the competent authorities, beforecommencingsuchuse,anotificationcontainingatleasttheinformationlistedinAnnexV,PartA.
Article 8
Following the notification referred to in Article 7, subsequent class 1
contained use may proceed without further notification. Users ofGMMs in class 1 contained uses shall be required to keep the record
of each assessment referred to in Article 5(6), which shall be made
availabletothecompetentauthorityonrequest.
Article 9
1. For first and subsequent class 2 contained usesto be carried out
in premises notified in accordance with Article 7, a notification
containing the information listed in Annex V, Part B shall besubmitted.
2. Ifthepremiseshavebeenthesubjectofapreviousnotificationto
carryoutclass2orahigherclassofcontainedusesandanyassociated
consent requirements have been satisfied, the class 2 contained usemayproceedimmediatelyfollowingthenewnotification.
The applicant can, however, himself request a decision on a formal
authorisation from the competent authority. The decision must be
madewithinamaximumof45daysfromthenotification.
3. If the premises have not been the subject of a previous notifica-
tiontocarryoutclass2orahigherclassofcontaineduses,theclass2contained use may, in the absence of any indication to the contrary1990L0219—EN—20.11.2003—004.001—5
▼M2
fromthecompetent authority,proceed45daysaftersubmissionofthe
notificationreferredtoinparagraph1,orearlierwiththeagreementofthecompetentauthority.
Article 10
1. For first and subsequent class 3 or class 4 contained uses to be
carried outinpremises notified inaccordance with Article 7,anotifi-cation containing the information listed in Annex V, Part C shall besubmitted.
2. A class 3 or higher class of contained use may not proceed
without the prior consent of the competent authority which shall
communicateitsdecisioninwriting:
(a) atthelatest45daysaftersubmissionofthenewnotification,inthe
caseofpremiseswhichhavebeenthesubjectofapreviousnotifi-cation tocarry outclass 3ora higher class ofcontained usesandwhere anyassociated consent requirements have been satisfied for
the same orahigher classthan the contained usewithwhichit is
intendedtoproceed;
(b) at the latest 90 days after submission of the notification, in other
cases.
Article 11
1. MemberStatesshalldesignatetheauthorityorauthoritiescompe-
tenttoimplementthemeasureswhichtheyadoptinapplicationofthisDirective and to receive and acknowledge the notifications referred toinArticles7,9and10.
2. The competent authorities shall examine the conformity of the
notifications with the requirements of this Directive, the accuracy and
completeness of the information given, the correctness of the assess-ment referred to in Article 5(2) and the class of contained uses and,whereappropriate, thesuitability ofthecontainment andother protec-tive measures, the waste management, and emergency response
measures.
3. Ifnecessary,thecompetentauthoritymay:
(a) asktheusertoprovidefurtherinformationortomodifythecondi-
tionsoftheproposedcontaineduseortoamendtheclassassignedto the contained use(s). In this case the competent authority mayrequire that the contained use, if proposed, does not begin, or, if
in progress, is suspended or terminated, until the competent
authorityhasgivenitsapprovalonthebasisofthefurtherinforma-tionobtainedorofthemodifiedconditionsofthecontaineduse;
(b) limit the time for which the contained use should be permitted or
subjectittocertainspecificconditions.
4. ForthepurposeofcalculatingtheperiodsreferredtoinArticles9
and10,anyperiodoftimeduringwhichthecompetentauthority:
— is awaiting any further information which it may have requested
fromthenotifierinaccordancewithparagraph3(a),or
— is carrying out a public inquiry or consultation in accordance with
Article13
shallnotbetakenintoaccount.
Article 12
Iftheuserbecomesawareofrelevantnewinformationormodifiesthe
contained useinawaywhichcouldhavesignificantconsequencesfor
therisksposedbyit,thecompetentauthorityshallbeinformedassoonaspossibleandthenotificationpursuanttoArticles7,9and10shallbemodified.
If information subsequently becomes available to the competent
authoritywhichcouldhavesignificantconsequencesfortherisksposed1990L0219—EN—20.11.2003—004.001—6
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by the contained use, the competent authority may require the user to
modifytheconditionsof,orsuspendorterminate,thecontaineduse.
Article 13
WhereaMemberStateconsidersitappropriate,itmayprovidethatthe
public shall be consulted on aspects of the proposed contained use,
withoutprejudicetoArticle19.
Article 14
The competent authorities shall ensure that before a contained use
commences:
(a) anemergencyplanisdrawnupforcontaineduseswherefailureof
the containment measures could lead to serious danger, whetherimmediate or delayed, to humans outside the premises and/or to
the environment, except where such an emergency plan has been
drawnupunderotherCommunitylegislation;
(b) informationonsuchemergencyplans,includingtherelevantsafety
measures to be applied, is supplied in an appropriate manner, andwithouttheirhavingtorequestit,tobodiesandauthoritiesliabletobe affected by the accident. The information shall be updated atappropriateintervals.Itshallalsobemadepubliclyavailable.
TheMemberStatesconcernedshallatthesametimemakeavailableto
other Member States concerned, as a basis for all necessary consulta-tion within the framework of their bilateral relations, the sameinformationasthatwhichisdisseminatedtotheirnationals.
Article 15
1. Member States shall take the necessary measures to ensure that,
intheeventofanaccident,theusershallberequiredtoinformimme-
diatelythecompetentauthorityspecifiedinArticle11andprovidethe
followinginformation:
— thecircumstancesoftheaccident,
— theidentityandquantitiesoftheGMMsconcerned,— any information necessary to assess the effects of the accident on
thehealthofthegeneralpopulationandtheenvironment,
— themeasurestaken.
2. Whereinformationisgivenpursuanttoparagraph1,theMember
Statesshallberequiredto:
— ensurethatanymeasuresnecessaryaretaken,andimmediatelyalert
anyMemberStateswhichcouldbeaffectedbytheaccident,
— collect,wherepossible,theinformationnecessaryforafullanalysis
of the accident and, where appropriate, make recommendations toavoidsimilaraccidentsinthefutureandtolimittheeffectsthereof.
Article 16
1. MemberStatesshallberequiredto:
(a) consultwithotherMemberStates,likelytobeaffectedintheevent
of an accident, on the proposed implementation of emergency
plans;
(b) informtheCommissionassoonaspossibleofanyaccident within
the scope of this Directive, giving details of the circumstances ofthe accident, the identity and quantities of the GMMs concerned,theresponsemeasurestakenandtheireffectivenessandananalysisoftheaccident, includingrecommendations tolimit itseffects andavoidsimilaraccidentsinthefuture.
2. The Commission, in consultation with the Member States, shall
establishaprocedurefortheexchangeofinformationpursuanttopara-graph 1. It shall also set up and keep at the disposal of the MemberStates a register of accidents within the scope of this Directive,1990L0219—EN—20.11.2003—004.001—7
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includingananalysisofthecausesoftheaccidents,experiencegained
andmeasurestakentoavoidsimilaraccidentsinthefuture.
Article 17
Member States shall ensure that the competent authority organizes
inspectionsandothercontrolmeasurestoensureusercompliancewiththisDirective.
Article 18
1. MemberStatesshallsendtotheCommission,attheendofeach
year, a summary report on class 3 and class 4 contained usesnotified
during that year pursuant to Article 10 including the description,
purposeandrisksofthecontaineduse(s).
2. Every three years, Member States shall send the Commission a
summary report on their experience with this Directive, the first timebeingon5June2003.
3. Everythreeyears,theCommissionshallpublishasummarybased
onthereportsreferredtoinparagraph2,thefirsttimebeingon5June2004.
4. The Commission may publish general statistical information on
the implementation of this Directive and related matters, as long as it
contains no information likely to cause harm to the competitive posi-
tionofauser.
Article 19
1. Where its disclosure affects one or more of the items mentioned
inArticle3(2)ofCouncilDirective90/313/EECof7June1990onthefreedom of access to information on the environment(
1), the notifier
mayindicatetheinformationinthenotificationssubmittedpursuantto
thisDirectivethatshouldbetreatedasconfidential.Verifiablejustifica-tionmustbegiveninsuchcases.
2. The competent authority shall decide, after consultation with the
notifier, which information will be kept confidential and shall inform
thenotifierofitsdecision.
3. In no case may the following information, when submitted
accordingtoArticles7,9or10,bekeptconfidential:
— the general characteristics of the GMMs, name and address of the
notifier,andlocationofuse,
— classofcontaineduseandmeasuresofcontainment,— the evaluation of foreseeable effects, in particular any harmful
effectsonhumanhealthandtheenvironment.
4. The Commission and the competent authorities shall not divulge
tothirdpartiesanyinformationdecidedtobeconfidentialaccordingto
paragraph2andnotifiedorotherwiseprovidedpursuanttothisDirec-tive, and shall protect intellectual property rights relating to the datareceived.
5. If, for whatever reasons, the notifier withdraws the notification,
thecompetentauthoritymustrespecttheconfidentialityoftheinforma-
tionsupplied.
Article 20
Amendments necessary toadapt AnnexII, PartA,and AnnexesIII to
VtotechnicalprogressandtoadaptAnnexII,PartC,shallbedecidedinaccordancewiththeprocedurelaiddowninArticle21.1990L0219—EN—20.11.2003—004.001—8
(1) OJL158,23.6.1990,p.56.▼B
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Article 20a
Before5December2000AnnexII,PartB,listingthecriteriaforinclu-
sionoftypesofGMMsintoAnnexII,PartC,shallbeadoptedbythe
Council acting byqualified majority on a proposal from the Commis-
sion.AmendmentstoAnnexII,PartB,shallbeadoptedbytheCouncilactingbyqualifiedmajorityonaproposalfromtheCommission.
Article 21
1. TheCommissionshallbeassistedbyacommittee.2. WherereferenceismadetothisArticle,Articles5and7ofDeci-
sion 1999/468/EC(
1) shall apply, having regard to the provisions of
Article8thereof.
TheperiodlaiddowninArticle5(6)ofDecision1999/468/ECshallbe
setatthreemonths.
3. TheCommitteeshalladoptitsrulesofprocedure.
Article 22
Member States shall bringinto force the laws,regulations andadmin-
istrative provisions necessary to comply with this Directive not laterthan 23 October 1991. They shall forthwith inform the Commissionthereof.
Article 23
ThisDirectiveisaddressedtotheMemberStates.1990L0219—EN—20.11.2003—004.001—9
(1) CouncilDecision1999/468/ECof28June1999layingdowntheprocedures
forthe exercise ofimplementing powersconferred onthe Commission(OJ
L184,17.7.1999,p.23).▼M4
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ANNEX I
PARTA
TechniquesofgeneticmodificationreferredtoinArticle2(b)(i)are, inter alia:
1. Recombinantnucleicacidtechniquesinvolvingtheformationofnewcombi-
nations of genetic material by the insertion of nucleic acid molecules
produced by whatever means outside an organism, into any virus, bacterial
plasmid or other vector system and their incorporation into a hostorganism
in which they do not naturally occur but in which they are capable of
continuedpropagation.
2. Techniques involving the direct introduction into a micro-organism of heri-
table material prepared outside the micro-organism including micro-
injection,macro-injectionandmicro-encapsulation.
3. Cell fusion or hybridisation techniques where live cells with new combina-
tions of heritable genetic material are formed through the fusion of two or
morecellsbymeansofmethodsthatdonotoccurnaturally.
PARTB
Techniques referred to in Article 2(b)(ii) which are not considered to result in
geneticmodification,onconditionthattheydonotinvolvetheuseofrecombi-
nant-nucleic acid molecules or GMMs made by techniques/methods other than
techniques/methodsexcludedbyAnnexII,PARTA:
(1)invitrofertilisation;
(2) naturalprocessessuchas:conjugation,transduction,transformation;
(3) polyploidyinduction.1990L0219—EN—20.11.2003—004.001—10
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ANNEX II
PARTA
Techniques ormethods ofgenetic modification yielding micro-organisms to be
excludedfromtheDirectiveontheconditionthattheydonotinvolvetheuseof
recombinant-nucleicacidmoleculesorGMMsotherthanthoseproducedbyone
ormoreofthetechniques/methodslistedbelow:
1. Mutagenesis.
2. Cellfusion(includingprotoplastfusion)ofprokaryoticspeciesthatexchange
geneticmaterialbyknownphysiologicalprocesses.
3. Cell fusion (including protoplast fusion) of cells of any eukaryotic species,
includingproductionofhybridomasandplantcellfusions.
4. Self-cloningconsistingintheremovalofnucleic acidsequencesfromacell
of an organism which may or may not be followed by reinsertion of all or
part of that nucleic acid (or a synthetic equivalent) with or without prior
enzymic or mechanical steps, into cells of the same species or into cells of
phylogeneticallycloselyrelatedspecieswhichcanexchangegeneticmaterial
by natural physiological processes where the resulting micro-organism is
unlikelytocausediseasetohumans,animalsorplants.
Self-cloning may include the use of recombinant vectors with an extended
historyofsafeuseintheparticularmicro-organisms.
PARTB
Criteria establishing the safety of GMMs for human health and the envir-
onment
ThisAnnexdescribesingeneral termsthe criteria tobemetwhenestablishing
the safety of types of GMMs for human health and the environment and their
suitability for inclusion in Part C. It will be supplemented by guidance notes
for the easy application of such criteria, such notes being developed and, if
necessary, amended by the Commission in accordance with the procedure
referredtoinArticle21.
1. INTRODUCTION
Typesofgeneticallymodifiedmicro-organisms(GMMs)listedinPartC
in accordance withthe procedure referred to in Article 21 are excluded
fromthe scope of this Directive. GMMs will be added to the list on a
case-by-case basis and exclusion will relate only to each clearly identi-
fied GMM. This exclusion applies only when the GMM is used under
conditionsofcontained useasdefinedinArticle 2(c).Itdoesnotapply
tothedeliberatereleaseofGMMs.ForaGMMtobelistedinPartC,it
mustbeprovedthatitmeetsthecriteriagivenbelow.
2. GENERALCRITERIA2.1.Strainverification/authentication
Identityofthestrainmustbepreciselyestablished.Modificationmustbe
knownandverified.
2.2.Documentedandestablishedevidence ofsafety
Documentedevidenceofthesafetyoftheorganismmustbeprovided.
2.3.Geneticstability
Whereanyinstabilitycouldadverselyaffectsafety,evidenceofstability
isrequired.
3. SPECIFICCRITERIA3.1.Non-pathogenic
TheGMMshouldnotbecapableofcausingdiseaseorharmtoahealthy
human, plant or animal. Since pathogenicity includes both toxigenicity
andallergenicity,theGMMshouldthereforebe:1990L0219—EN—20.11.2003—004.001—11
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3.1.1.Non-toxigenic
The GMM should not produce increased toxigenicity as a result of the
geneticmodificationnorbenotedforitstoxigenicproperties.
3.1.2.Non-allergenic
The GMMshould not produce increased allergenicity as a result of the
geneticmodificationnorbeanotedallergen,having,forexample,aller-
genicity comparable in particular with that of the micro-organisms
identifiedinCouncilDirective93/88/EECof12October1993amending
Directive90/679/EEContheprotectionofworkersfromrisksrelatedto
exposuretobiologicalagentsatwork(1).
3.2.Noharmfuladventitiousagents
The GMM should not harbour known harmful adventitious agents such
as other micro-organisms, active or latent, existing alongside or inside
theGMMthatcouldcauseharmtohumanhealthandtheenvironment.
3.3.Transferofgeneticmaterial
The modified genetic material must not give rise to harm if transferred
norshoulditbe selftransmissible ortransferable at afrequency greater
thanothergenesoftherecipientorparentalmicro-organism.
3.4.Safety for the environment in the event of a significant and unin-
tendedrelease
GMMsmustnotproduceadverseeffectsontheenvironment,immediate
or delayed, should any incident involving a significant and unintended
releaseoccur.
GMMsthat do not meet the above criteria may not be included in Part
C.
PARTC
TypesofGMMswhichmeetthecriterialistedinPartB:
…(tobecompletedinaccordancewiththeprocedureinArticle21)1990L0219—EN—20.11.2003—004.001—12
(1) OJL268,29.10.1993,p.71.▼M2
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ANNEX III
PRINCIPLES TO BE FOLLOWEDFOR THE ASSESSMENT
REFERREDTOINARTICLE5(2)
This Annex describes in general terms the elements to be considered and the
procedure tobefollowed toperformthe assessmentreferred toinArticle 5(2).
Itwillbesupplemented,asregardsinparticularsectionB,byguidancenotesto
be developed by the Commission in accordance with the procedure set out in
Article21.
Theseguidancenotesshallbecompletednolaterthan5June2000.
A. ELEMENTSOFASSESSMENT
1. Thefollowingshouldbeconsideredaspotentiallyharmfuleffects:
— diseasetohumansincludingallergenicortoxiceffects,
— diseasetoanimalsorplants,— deleterious effects due to the impossibility of treating a disease or
providinganeffectiveprophylaxis,
— deleterious effects due to establishment or dissemination in the environ-
ment,
— deleteriouseffectsduetothenaturaltransferofinsertedgeneticmaterial
tootherorganisms.
2. TheassessmentreferredtoinArticle5(2)shouldbebasedonthefollowing:
(a) the identification of any potentially harmful effects, in particular those
associatedwith:
(i) therecipientmicro-organism;
(ii) thegeneticmaterialinserted(originatingfromthedonororganism);
(iii) thevector;
(iv) the donor micro-organism (as long as the donor micro-organism is
usedduringtheoperation);
(v) theresultingGMM;
(b) thecharacteristicsoftheactivity;
(c) theseverityofthepotentiallyharmfuleffects;
(d) thelikelihoodofthepotentiallyharmfuleffectsbeingrealised.
B. PROCEDURE
3. The first stage in the assessment process should be to identify the harmful
propertiesoftherecipientand,whereappropriate,thedonormicro-organism,
any harmful properties associated with the vector or inserted material,
includinganyalterationintherecipient'sexistingproperties.
4. In general, only GMMs which show the following characteristics would be
consideredappropriateforinclusioninclass1asdefinedinArticle5:
(i) the recipient or parental micro-organism isunlikely to cause disease to
humans,animalsorplants(
1);
(ii) thenatureofthevectorandtheinsertissuchthattheydonotendowthe
GMM with a phenotype likely to cause disease to humans, animals or
plants(1),orlikelytocausedeleteriouseffectsintheenvironment;
(iii) the GMM is unlikely to cause disease to humans, animals or plants(1)
andisunlikelytohavedeleteriouseffectsontheenvironment.
5. In order to obtain the necessary information to implement this process the
user may firstly take into account relevant Community legislation (in parti-
cular Council Directive 90/679/EEC(2)). International or national
classification schemes(e.g.WHO,NIH,etc.)andtheirrevisionsduetonew
scientificknowledgeandtechnicalprogressmayalsobeconsidered.
These schemes concern natural micro-organisms and as such are usually
basedontheabilityofmicro-organismstocausediseasetohumans,animals
or plants and on the severity and transmissibility of the disease likely to be
caused. Directive 90/679/EEC classifies micro-organisms, as biological
agents,intofourclassesofriskonthebasisofpotentialeffectsonahealthy
humanadult.Theseclassesofriskcanbeusedasguidancetothecategorisa-1990L0219—EN—20.11.2003—004.001—13
(1) Thiswouldonlyapplytoanimalsandplantsintheenvironmentlikelytobeexposed.
(2) OJL374,31.12.1990,p.1.DirectiveaslastamendedbyCommissionDirective97/59/
EC(OJL282,15.10.1997,p.33).
▼M2
tion of the contained use activities in the four classes of risk referred to in
Article5(3).Theusermayalsotakeintoconsiderationclassificationschemes
referring to plant and animal pathogens (which are usually established on a
national basis). The abovementioned classification schemes give only a
provisional indication ofthe riskclass ofthe activity and the corresponding
setofcontainmentandcontrolmeasures.
6. The hazard identification process carried out in accordance with paragraphs
3 to 5, should lead to the identification of the level of risk associated with
theGMM.
7. Selection of the containment and other protective measures should then be
made on the basis of the level or risk associated with the GMMs together
withconsiderationof:
(i) thecharacteristicsoftheenvironmentlikelytobeexposed(e.g.whether
intheenvironment likelytobeexposedtotheGMMsthere areknown
biota which can be adversely affected by the micro-organisms used in
thecontaineduseactivity);
(ii) thecharacteristicsoftheactivity(e.g.itsscale;nature);
(iii) any non-standard operations (e.g. the inoculation of animals with
GMMs;equipmentlikelytogenerateaerosols).
Consideration of items (i) to (iii) for the particular activity may increase,
reduceorleaveunalteredthelevelofriskassociatedwiththeGMMasiden-
tifiedunderparagraph6.
8. The analysis carried out as described above will finally lead to the assign-
mentoftheactivitytooneoftheclassesdescribedinArticle5(3).
9. The final classification of the contained use should be confirmed by
reviewingthecompletedassessmentreferredtoinArticle5(2).1990L0219—EN—20.11.2003—004.001—14
▼M2
ANNEX IV
CONTAINMENTANDOTHERPROTECTIVEMEASURES
General principles
1. Thesetablespresentthenormalminimumrequirementsandmeasuresneces-
saryforeachlevelofcontainment.
Containment is also achieved through the use of good work practices,
training,containmentequipmentandspecialinstallationdesign.Forallactiv-
itiesinvolvingGMMstheprinciplesofgoodmicrobiologicalpracticeandthe
followingprinciplesofgoodoccupationalsafetyandhygiene,shallapply:
(i) to keep workplace and environmental exposure to any GMM to the
lowestpracticablelevel;
(ii) to exercise engineering control measures at source and to supplement
these with appropriate personal protective clothing and equipment
whennecessary;
(iii) totestadequatelyandmaintaincontrolmeasuresandequipment;
(iv) to test, when necessary, for the presence of viable process organisms
outsidetheprimaryphysicalcontainment;
(v) toprovideappropriatetrainingofpersonnel;
(vi) toestablishbiologicalsafetycommitteesorsubcommittees,ifrequired;
(vii) to formulate and implement local codes of practice for the safety of
personnel,asrequired;
(viii) whereappropriatetodisplaybiohazardsigns;
(ix) toprovidewashinganddecontaminationfacilitiesforpersonnel;
(x) tokeepadequaterecords;
(xi) toprohibiteating,drinking,smoking,applyingcosmeticsorthestoring
offoodforhumanconsumptionintheworkarea;
(xii) toprohibitmouthpipetting;
(xiii) to provide written standard operating procedures where appropriate to
ensuresafety;
(xiv) to have effective disinfectants and specified disinfection procedures
availableincaseofspillageofGMMs;
(xv) to provide safe storage for contaminated laboratory equipment and
materials,whenappropriate.
2. Thetitlesofthetablesareindicative:
TableIApresentsminimumrequirementsforlaboratoryactivities.Table I B presents additions to and modifications of Table I A for glass-
house/growth-roomactivitiesinvolvingGMMs.
TableICpresentsadditionstoandmodifications ofTableIAforactivities
withanimalsinvolvingGMMs.
Table II presents minimum requirements for activities other than laboratory
activities.
In some particular cases, it might be necessary to apply a combination of
measures,fromTableIAandTableII,ofthesamelevel.
Insomecasesusersmay,withtheagreementofthecompetentauthority,not
applyaspecification underaparticular containment levelorcombine speci-
ficationsfromtwodifferentlevels.
Inthesetables‘optional’meansthattheusermayapplythesemeasuresona
case-by-casebasis,subjecttotheassessmentreferredtoinArticle5(2).
3. Memberstatesmay,inimplementingthisAnnex,incorporateinadditionthe
generalprinciplesinparagraphs1and2inthefollowingtablesforthesake
ofclarityoftherequirements.1990L0219—EN—20.11.2003—004.001—15
▼M2
Table I A
Containmentandotherprotective measuresforlaboratoryactivities
SpecificationsContainmentlevels
1234
1 Laboratorysuite:isolation(1) Not
requiredNot
requiredRequired Required
2 Laboratory:sealableforfumigation Not
requiredNot
requiredRequired Required
Equipment
3 Surfaces resistant to water, acids,
alkalis, solvents, disinfectants,
decontaminationagentsandeasyto
cleanRequired
(bench)Required
(bench)Required
(bench,
floor)Required
(bench,
floor,
ceiling,
walls)
4 Entrytolabviaairlock(2) Not
requiredNot
requiredOptional Required
5 Negative pressure relative to the
pressure of the immediate environ-
mentNot
requiredNot
requiredRequired
except
for(3)Required
6 Extract and input air fromthe
laboratoryshouldbeHEPA-filteredNot
requiredNot
requiredRequired
(HEPA)(4)
—extract
airexcept
for(3)Required
(HEPA)(5)
—input
andextract
air
7 Microbiologicalsafetypost Not
requiredOptional Required Required
8 Autoclave Onsite Inthe
buildingEnsuite(6) Inlab=
double-
ended
Systemofwork
9 Restrictedaccess Not
requiredRequired Required Required
10 Biohazardsignonthedoor Not
requiredRequired Required Required
11 Specific measures to control
aerosoldisseminationNot
requiredRequired
minimiseRequired
preventRequired
prevent
13 Shower Not
requiredNot
requiredOptional Required
14 ProtectiveclothingSuitable
protective
clothingSuitable
protective
clothingSuitable
protective
clothing
and
(optional)
footwearComplete
changeof
clothing
andfoot-
wearbefore
entryand
exit
15 GlovesNot
requiredOptional Required Required1990L0219—EN—20.11.2003—004.001—16
▼C1
▼M2
▼M2
SpecificationsContainmentlevels
1234
18 Efficient vector control (e.g. for
rodentsandinsects)Optional Required Required Required
Waste
19 Inactivation of GMMs in effluent
fromhand-washing sinks or drains
andshowersandsimilareffluentsNot
requiredNot
requiredOptional Required
20 Inactivation of GMMs in contam-
inedmaterialandwasteOptional Required Required Required
Othermeasures
21 Laboratory to contain its own
equipmentNot
requiredNot
requiredOptional Required
23 An observation window or alterna-
tive is to be present so that
occupantscanbeseenOptional Optional Optional Required
(1) Isolation = thelaboratoryisseparatedfromotherareasinthesamebuildingorisinaseparatedbuilding.
(2) Airlock = entrymustbethroughanairlockwhichisachamberisolatedfromthelaboratory.Thecleansideof
the airlock must be separated from the restricted side by changing or showering facilities and preferably byinterlockingdoors.
(
3) Activitieswheretransmissiondoesnotoccurviaairborneroute.
(4) HEPA = Highefficiencyparticulate air.
(5) WhereviruseswhicharenotretainedbyHEPAfiltersareused,extrarequirementswillbenecessaryforextract
air.
(6) Withvalidatedprocedures,allowingthesafetransferofmaterialintoanautoclaveoutsidethelab,andproviding
anequivalentlevelofprotection.
Table I B
Containmentandotherprotective measuresforglasshousesandgrowth-rooms
Theterms‘glasshouse’and‘growth-room’refertoastructurewithwalls,aroofandafloordesigned
andusedprincipallyforgrowingplantsinacontrolledandprotectedenvironment.
AllprovisionsofTableIAshallapplywiththefollowingadditions/modifications:
SpecificationsContainmentlevels
1234
Building
1 Greenhouse:permanentstructure(1) Not
requiredRequired Required Required
Equipment
3 Entry via a separated roomwith
twointerlockingdoorsNot
requiredOptional Optional Required
4 Control of contaminated run-off
waterOptional Mini-
mise(2)
run-offPrevent
run-offPrevent
run-off
Systemofwork
6 Measures to control undesired
species such as insects, rodents,
arthropodsRequired Required Required Required1990L0219—EN—20.11.2003—004.001—17
▼M2
SpecificationsContainmentlevels
1234
7 Procedures for transfer of living
material between the glasshouse/
growth-room, protective structure
and laboratory shall control disse-
mination of genetically modified
micro-organismsMinimise
dissemina-
tionMinimise
dissemina-
tionPrevent
dissemina-
tionPrevent
dissemina-
tion
(1) Theglasshouseshallconsistofapermanentstructurewithacontinuouswaterproofedcovering,locatedonasite
gradedtoprevententryofsurface-waterrun-offhavingself-closinglockabledoors.
(2) Wheretransmissioncanoccurthroughtheground.
Table I C
Containmentandotherprotective measuresforactivities inanimalunits
AllprovisionsofTableIAshallapplywiththefollowingadditions/modifications:
SpecificationsContainmentlevels
1234
Facilities
1 Isolationofanimalunit(1) Optional Required Required Required
2 Animal facilities(2) separated by
lockabledoorsOptional Required Required Required
3 Animalfacilitiesdesignedtofacili-
tate decontamination (waterproof
and easily washable material
(cages,etc.))Optional Optional Required Required
4 Floorand/orwallseasilywashable Optional Required
(floor)Required
(floorand
walls)Required
(floorand
walls)
5 Animals kept in appropriate
containment facilities such as
cages,pensortanksOptional Optional Optional Optional
6 Filters on isolators or isolated
room(3)Not
requiredOptional Required Required
(1) Animalunit: abuilding,orseparateareawithinabuildingcontainingfacilitiesandotherareassuchaschanging
rooms,showers,autoclaves,foodstorageareas,etc.
(2) Animalfacility: afacilitynormallyusedtohousestock,breedingorexperimentalanimalsoronewhichisused
fortheperformanceofminorsurgicalprocedures.
(3) Isolators: transparent boxes where small animals are contained within or outside a cage; for large animals,
isolatedroomsmaybemoreappropriate.
Table II
Containmentandotherprotectivemeasuresforotheractivities
SpecificationsContainmentlevels
1234
General
1 Viable micro-organisms should be
contained in a systemwhich sepa-
rates the process fromthe
environment(closedsystem)Optional Required Required Required1990L0219—EN—20.11.2003—004.001—18
▼M2
SpecificationsContainmentlevels
1234
2 Control of exhaust gases fromthe
closedsystemNot
requiredRequired,
minimise
dissemina-
tionRequired,
prevent
dissemina-
tionRequired,
prevent
dissemina-
tion
3 Control of aerosols during sample
collection,additionofmaterialtoa
closed systemor transfer of m ate-
rialtoanotherclosedsystemOptional Required,
minimise
dissemina-
tionRequired,
prevent
dissemina-
tionRequired,
prevent
dissemina-
tion
4 Inactivation of bulk culture fluids
before removal from the closed
systemOptional Required,
byvali-
dated
meansRequired,
byvali-
dated
meansRequired,
byvalidated
means
5 Seals should be designed so as to
minimiseorpreventreleaseNosepe-
cific
requirementMinimise
dissemina-
tionPrevent
dissemina-
tionPrevent
dissemina-
tion
6 The controlled area should be
designed to contain spillage of the
entirecontentsoftheclosedsystemOptional Optional Required Required
7 Thecontrolled areashouldbeseal-
abletopermitfumigationNot
requiredOptional Optional Required
Equipment
8 Entryviaairlock Not
requiredNot
requiredOptional Required
9 Surfaces resistant to water, acids,
alkalis, solvents, disinfectants,
decontaminationagentsandeasyto
cleanRequired
(benchif
any)Required
(benchif
any)Required
(benchif
any,floor)Required
(bench,
floor,
ceiling,
walls)
10 Specific measures to adequately
ventilate the controlled area in
ordertominimiseaircontaminationOptional Optional Optional Required
11 The controlled area should be
maintained atan airpressurenega-
tivetotheimmediatesurroundingsNot
requiredNot
requiredOptional Required
12 Extract and input air fromthe
controlled area should be HEPA
filteredNot
requiredNot
requiredRequired
(extractair,
optionalfor
inputair)Required
(inputand
extractair)
Systemofwork
13 Closed systems should be located
withinacontrolledareaNot
requiredOptional Required Required
14 Access should be restricted to
nominatedpersonnelonlyNot
requiredRequired Required Required
15 Biohazardsignsshouldbeposted Not
requiredRequired Required Required
17 Personnel should shower before
leavingthecontrolledareaNot
requiredNot
requiredOptional Required1990L0219—EN—20.11.2003—004.001—19
▼M2
SpecificationsContainmentlevels
1234
18 Personnel should wear protective
clothingRequired
(work
clothing)Required
(work
clothing)Required Complete
change
beforeexit
andentry
Waste
22 Inactivation of GMMs in effluent
fromhandwashing sinks and
showersorsimilareffluentsNot
requiredNot
requiredOptional Required
23 Inactivation of GMMs in contami-
nated material and waste including
those in process effluent before
finaldischargeOptional Required,
byvali-
dated
meansRequired,
byvali-
dated
meansRequired,
byvalidated
means1990L0219—EN—20.11.2003—004.001—20
▼M2
ANNEX V
PARTA
InformationrequiredforthenotificationreferredtoinArticle7:
— nameofuser(s)includingthoseresponsibleforsupervisionandsafety,
— informationonthetrainingandqualificationsofthepersonsresponsiblefor
supervisionandsafety,
— detailsofanybiologicalcommitteesorsubcommittees,— addressandgeneraldescriptionofthepremises,— adescriptionofthenatureoftheworkwhichwillbeundertaken,— theclassofthecontaineduses,
— onlyforclass1containeduses,asummaryoftheassessmentreferredtoin
Article5(2)andinformationonwastemanagement.
PARTB
InformationrequiredforthenotificationreferredtoinArticle9:
— thedateofsubmissionofthenotificationreferredtoinArticle7,
— thenameofthepersonsresponsibleforsupervisionandsafetyandinforma-
tiononthetrainingandqualification,
— the recipient, donor and/or parental micro-organism(s) used and, where
applicable,thehost-vectorsystem(s)used,
— thesource(s)andtheintendedfunction(s)ofthegeneticmaterial(s)involved
inthemodification(s),
— identityandcharacteristicsoftheGMM,— thepurposeofthecontaineduseincludingtheexpectedresults,— approximateculturevolumestobeused,— description ofthecontainment andother protective measurestobe applied,
including information about waste management including the wastes to be
generated,theirtreatment,finalformanddestination,
— asummaryoftheassessmentreferredtoinArticle5(2),
— theinformationnecessaryforthecompetentauthoritytoevaluateanyemer-
gencyresponseplansifrequiredunderArticle14.
PARTC
InformationrequiredforthenotificationreferredtoinArticle10:
(a) — thedateofsubmissionofthenotificationreferredtoinArticle7,
— thenameofthepersonsresponsibleforsupervisionandsafetyandinfor-
mationonthetrainingandqualification;
(b) — therecipientorparentalmicro-organism(s)tobeused,
— thehost-vectorsystem(s)tobeused(whereapplicable),
— the source(s) and intended functions(s) of the genetic material(s)
involvedinthemodification(s),
— identityandcharacteristicsoftheGMM,— theculturevolumestobeused;
(c) — description of the containment and other protective measures to be
applied, including information about waste management including the
typeandformofwastestobegenerated,theirtreatment,finalformand
destination,
— thepurposeofthecontaineduseincludingtheexpectedresults,
— descriptionofthepartsoftheinstallation;
(d) information about accident prevention and emergency response plans, if
any:
— anyspecifichazardsarisingfromthelocationoftheinstallation,
— the preventive measures applied such as safety equipment, alarm
systemsandcontainmentmethods,
— procedures and plans for verifying the continuing effectiveness of the
containmentmeasures,
— adescriptionofinformationprovidedtoworkers,— the information necessary for the competent authority to evaluate any
emergencyresponseplansifrequiredunderArticle14;
(e) acopyoftheassessmentreferredtoinArticle5(2).1990L0219—EN—20.11.2003—004.001—21