Proposal for a COUNCIL DIRECTIVE amending Directive 90/219/EEC on the contained use of genetically modified micro-organisms
Date: 1995-12-06
Institutions: European Commission
Subjects: bio-industry, genetic engineering, genetically modified organism, occupational safety, preparation for market, public health

Mi 

COMMISSION  OF THE  EUROPEAN  COMMUNITIES 

Brussels, 06.12.1995 
COM(95)  640  final 

95/0340  (CNS) 

Proposal  for a 
COUNCIL DIRECTIVE 
amending  Directive 90/219/EEC 
on the contained  use of  genetically  modified  micro-organisms 

(presented  by the  Commission) 

B 

if? 

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^«jfH'.ftà-;.; 

EXPLANATORY  MEMORANDUM 

1. 

Introduction and Summary 

1.1  The need for a revision  of  Directive  90/219/EEC 

Directive 90/219/EEC relating to the contained use of genetically  modified  micro 
organisms  was proposed  and  adopted  together  with  Directive  90/220/EEC  on  the 
deliberate  release  into  the  environment  of  genetically  modified  organisms  in  a 
horizontal  way on the  principle that a precautionary  approach as regards safety  to 
human health  and the  environment  should be followed  in order to ensure that  the 
expected  benefits  of  this  technology  can  develop  safely. 

The  basis  for  Directive  90/219/EEC  was  the  scientific  knowledge  of  the  early 
1980s  and  most  particularly  the  limited  experience  of  that  time  with  industrial 
applications. 

While  ensuring  that  the  techniques  of  genetic  modification  are  used  in  a 
responsible  way,  we  must  at the same time take  into  account  the wider  scientific 
knowledge  and  experience  gained  over the  last  ten years. 

Since  the  early  1980s  the  techniques  of  genetic  modification  have  been  used 
extensively  in  many  research  laboratories  and  industrial  facilities  worldwide,  as 
a  result  of  which  there  is now scientific  evidence pointing  to the  safety  of  many 
types  of  activities  involving  genetically  modified  micro-organisms,  which  can, 
therefore,  be  carried  out  safely  in  contained  facilities  by  applying  normal  good 
laboratory  practices. 

The  Commission  has  mounted  an  extensive  and  systematic  review  of  the 
provisions  of  Directive  90/219/EEC  by  taking  into  account  not  only  the 
abovementioned  scientific  knowledge,  but  also  the  experience  gained  with  the 
implementation  of this Directive. In carrying out this review the Commission  was 
involved  in  extensive  consultation  with  interested  parties. 

The  review  identified  the  following  main  weaknesses  in  Directive  90/219/EEC: 

(i)  The  classification  system  for  GMMs  is  not  in  line  with  international 

practice. 

(ii)  The  administrative  procedures  and notification  requirements  are  not  linked 

to the  real  risk  of  activities. 

(iii)  The  administrative  procedures  for  certain  classes  of  activities  involving 

genetically  modified  micro-organisms  are  unnecessarily  restrictive. 

(iv)  There  is  insufficient  guidance  as to  the  containment  and  control  measures 
which  should  be  applied  in  order  to  protect  human  health  and  the 
environment. 

(v)  The  flexibility  of  the  Directive  is  limited  as  it  does  not  provide  for  easy 

adaptation  to  technical  progress  of one  of  its Technical  Annexes. 

The  Commission  considers that  it is now possible to propose  amendments  which 
will  address  the  weaknesses  of  the  Directive,  while  at  the  same  time  continuing 
to provide  the  same  level  of  protection  for  human  health  and  the  environment. 

Before  making  this  proposal  the  Commission  has  taken  into  consideration 
corresponding  regulations  in  other  parts  of  the  world  (e.g.  USA,  Canada)  and 
international  guidelines  (NIH,  OECD, WHO). 

1.2  Main elements  of  the  proposal 

In  essence  the  Commission  is proposing  the  following: 

(i)  The  administrative  procedures  and notification  requirements  will  be  linked 
to  the  risk  of  the  activities  involving  GMMs.  Four  classes  of  risk  will  be 
foreseen  as  judged  in  the  light  of  scientific  knowledge  and  international 
experience. 

. 

As  a  consequence,  the  current  non-risk  based  differential  treatment  of 
operations  for  administrative  purposes  will  be  abolished. 

(ii)  The  administrative  procedures  will  be  streamlined  where  this  does  not 

compromise  safety. 

(iii)  The minimum  containment  and control  measures to be applied  for  each risk 
class  will  be  further  specified,  thus  ensuring  harmonization  and  adequate 
environmental  protection. 

(iv)  The  possibility  for  further  exemptions  of  safe  genetically  modified  micro 
organisms  will  be  introduced,  thus  ensuring  rapid  adaptation  to  technical 
progress  and  avoidance  of  unjustified  administrative  burdens  on  users. 

(v)  All  Annexes  will  become  amendable  through  a  Regulatory  Committee 
procedure,  thus  enhancing  flexibility  and  permitting  timely  adaptation  of 
these highly  technical  parts of  the  Directive to  rapidly  advancing  scientific 
and  technical  progress. 

In  addition  to  the  abovementioned  main  modifications,  the  proposal  contains 
amendments which were considered necessary in order for the text to be consistent 
and  clear.  Furthermore,  it  was  considered  necessary,  to  up-date  some  technical 
parts  of  the  Directive  on  the  basis of  experience  and  scientific  progress. 

2. 

Presentation  of  changes  in the Articles  and the Annexes 

Article 2 

Paragraph  (a) 

It  has  been  considered  necessary  to  provide  some  further  technical  clarification 
concerning  the  definition  of  "micro-organism". 

Paragraphs  (d)  and  (e)  of  Directive  90/219/EEC  have  been  deleted,  since  the 
distinction  between  Type  A  and  Type  B  operations  was  not  based  on  any 
identified  risk. 

Paragraph  (c) 

The  definition  of  "contained  use" has  been  modified  as regards  disposal,  so  that 
the  disposal  of  genetically  modified  micro-organisms  originating 
from 
contained-use  activities  can  be  covered  and  evaluated  under  the  same  Directive 
that  covers  the  contained  use  of  such  GMMS. 

Article  3 

Given  the  pace  at  which  the  field  is  advancing,  it  has  been  considered  appropriate  to 
introduce  the  possibility  for  future  exemption  of  types  of  GMMs  other  than  those 
specified  already  in  Annex  II  A  once  evidence  of  their  safety  for  human  health  and  the 
environment  becomes  available. 

Article  4 

Paragraph  b 

The  use  of  genetically  modified  micro-organisms  which  have  been  placed  on  the 
market  following  the  procedures  of  Directive  90/220/EEC  or  of  other  Community 
legislation  which  provides  for  a specific  environmental  risk-assessment  similar  to 
that  laid  down  in  that  Directive,  will  be  exempted  from  Directive  90/219/EEC 
provided  that  the  contained  use  of  such  GMMs  is  in  accordance  with  the 
conditions,  if  any,  of  the  marketing  consent  or  approval  given  under 
the 
abovementioned  Community  legislation. 

This has been  considered  necessary  in order  to avoid  a situation  where  notification 
would  have  to  be  submitted  and  a  risk  assessment  would  have  to  be  carried  out 
in order  to  proceed  in particular  premises  with  uses of  GMMs  which  have  already 
been given  consent/approval  under  Community  legislation  providing  for  a  specific 
environmental  risk  assessment.  Such  a situation  would  be  unjustified  since  a  full 
assessment  of the approved  use(s) of such  GMMs  would have already  been  carried 
out  under  the  abovementioned  Community  legislation. 

Article  5 

Paragraph  3 

Activities involving  genetically  modified  micro-organisms  will be  subject  to a  risk 
*  assessment  which  should  result  in  the  categorization  of  activities  in  four  classes 
of  risk.  The  principles  on  which  the  risk  assessment  should  be  carried  out  are 
outlined  in  Annex  III. 

This  has  been  considered  necessary  since  all  internationally  accepted  guidelines 
and  other  Community  legislation  (Directive  90/679/EEC)  foresee  classification 
in  four  classes  of  risk.  In  this  way  low  and  high  risk  genetically  modified 
micro-organisms  will  no  longer  be  classified  in  the  same  group  and  be  subject  to 
the  same  administrative  procedures  as  is  currently  the  case. 

Given  the  emphasis  of  Directive  90/219/EEC  on  the  protection  of  human  health 
and  the  environment,  which  presupposes  the  application  of  containment  measures 
commensurate  to  risk,  each  risk  class  will  correspond  to  a  particular  level  of 
containment.  In  this  way  there  will  be  clear  provisions  as  to  the  minimum 
containment  measures  which  are  appropriate  for  each  risk  class,  which  is  not 
currently  the  case  for  low  to  high  risk  GMMs. 

Article  6 

Paragraph  1 

The  user  shall  apply  the  containment  and  control  measures  which  correspond  to 
the  risk  class of  the  activity,  so  that  a high  level  of  safety  is ensured  and  exposure 
to  any  genetically  modified  micro-organisms  is  kept  to  the  lowest  practicable 
level. 

Annex  IV  presents  four  Tables  outlining  the  normal  minimum  requirements  and 
measures  for  each  level  of  containment  and  for  different  types  of  activities. 
According  to  international  practice  these  measures  correspond  to  a high  level  of 
safety. 

Paragraph  2 

It has been  specified  that not  only the containment  and control  measures, but also 
the  risk  assessment  should  be  periodically  reviewed  in the light of new  scientific 
or  technical  knowledge  and  in  the  case of  significant  changes in the  activities. 

Articles  8, 9 and 10 

These Articles specify  the administrative procedures and notification  requirements which 
are  considered  appropriate  for  each  risk  class. More  specifically: 

Article 8 

Class  1  activities  will  be  able  to  commence  immediately  following  the  notification 
referred  to  in  Article  7,  which  should  include  at  least  the  information  outlined  in 
Annex VA. 

This  has  been  considered  appropriate  since  Class  1 activities  are  activities  of  no  or 
negligible  risk  and there  is no justification  for  a waiting  period before  commencement 
of  such  activities. 

The  Commission  believes  that  for  Class  1 activities  safety  for  human  health  and  the 
environment  is adequately  ensured  through  the  corresponding  containment  and  control 
measures  outlined  in  Annex  IV.  Furthermore,  competent  authorities  have  the  right  to 
control  at any time the correctness of the risk assessment and the adequacy of safety  and 
emergency  response  measures  as well  as the adequacy  of  waste management  according 
to  the  provisions  of  Article  11.  For  Class  1  activities,  control  by  the  competent 
authorities will be facilitated  by the obligation  imposed on users to keep records of each 
assessment. 

Article 9 

Class  2  activities  will  be  able  to  commence  following  submission  of  the  information 
outlined  in  Annex VB. 

If no previous notification  has been submitted for  Class 2 or higher class activities, work 
can  only  commence  45  days  after  submission  of  the  notification,  or  earlier  with  the 
agreement  of  the  competent  authority.  Such  a  waiting  period  has  been  considered 
necessary,  in order  for  the competent  authority  to be able to verify  if the users are able 
to  carry  out  the  risk  assessment  and  to  apply  the  appropriate  containment  and  control 
measures. 

If,  however,  a  previous  notification  has  been  submitted  for  Class  2  or  higher  class 
activities  and  the associated  consent  requirements  have been  satisfied,  the new  Class 2 
activity  can  commence  immediately  following  a  new  notification  containing  the 
information  outlined in Annex VB. This has been considered appropriate since users will 
have been able to demonstrate earlier their ability to carry out risk assessment and apply 
the  appropriate  control  and  containment  measures. 

Article  10 

Class  3  and  Class  4  activities  will  be  able  to  commence  following  submission  of  the 
information  outlined  in  Annex  VC. 

If no  previous  notification  has  been  submitted  for  the same  or higher  class  activities,  the 
contained  use  may  not  proceed  without  a  written  consent  of  the  competent  authority 
which  should  be  given  within  90  days  after  submission  of  the  notification.  If,  however, 
a  previous  notification  has  been  submitted  for  the  same  or  higher  class  of  activities  and 
the  associated  consent  requirements  have  been  satisfied,  then  the  new  activity  can  in  the 
absence  of  any  indication  to  the  contrary,  commence  45  days  after  submission  of  a  new 
notification  containing  the  information  outlined  in  Annex  VC.  This  has  been  considered 
appropriate  since  users  will  have  been  able  to  demonstrate  earlier  their  ability  to  carry 
out  risk  assessment  and  apply  the  appropriate  control  and  containment  measures. 

Article  11 

Competent  Authorities  appointed  by Member  States will  have the responsibility  not  only 
of  receiving  and  acknowledging  notifications,  but  also  of  examining  the  correctness  of 
the  risk  assessment  and  the  assignment  of  class  of  the  risk.  The  competent  authority 
may,  among  others,  ask  the  user  to  amend  the  class  of  risk  assigned  to  the  activity(ies) 
and  may  require  that  the  contained  use,  if  proposed  does  not  begin  or  if  in  progress  is 
halted. 

Article  14 

Paragraph  a 

Given  the  risk-based  approach  of  this  proposal,  it  has  been  considered  necessary  to 
define  on  the  basis  of  the  class  of  risk  the  activities  for  which  the  drawing  up  of 
emergency  response  plans  will  be  necessary.  It  has  also  been  considered  necessary  to 
further  clarify  the  circumstances  under  which  the  drawing-up  of  emergency  response 
plans  will  be necessary.  It has, therefore,  been  specified  that  emergency  plans  should  be 
drawn  up  for  Class  3  and  Class  4  activities  where  failure  of  the  containment  measures 
could  lead  to  serious  danger;  immediate  or  delayed  to  humans  outside  the  premises 
and/or  to  the  environment. 

Paragraph  b 

It  has  been  considered  necessary  to  clarify  that  information  on  emergency  plans  should 
be  supplied  to  bodies  and  authorities  likely  to  be  affected  by  an  accident. 

Article  15 

Paragraph  1 

Given  the  fact  that  it  might  not  always  be  possible  to  have  exact  information  on  the 
identity  and  the  quantities  of  GMMs  released  in  the  event  of  an  accident,  it  has  been 
considered  necessary  to  specify  that  in  the  event  of  an  accident  information  should  be 
given  on  the  identity  and  quantities  of  the  GMMs  concerned  (i.e.  involved  in  the 
contained  use  affected  by  the  accident). 

Article  16 

Paragraph  b 

Given  the  fact  that  it  might  not  be  always  possible  to  have  exact  information  on  the 
identity  and  the  quantities  of  GMMs  released  in  the  event  of  an  accident,  it  has  been 
considered  appropriate  to  specify  that  the  Commission  should  be  informed  of  the 
identity  and  the  quantities  of  the  GMMs  concerned  (i.e.  involved  in  the  contained  use 
affected  by  the  accident). 

Article  18 

Paragraph  1 

Given  the  new  risk-based  classification  system  outlined  in  Article  5, it  is proposed  that 
the  summary  reports to be  submitted  to the  Commission  by  Member  States should  cover 
Class  3  and  Class  4  activities. 

Article  19 

It  has  been  considered  necessary  to  bring  this  paragraph  in  line  with  the  modifications 
introduced  in  the  body  of  the  Directive  and  the  Annexes,  while  ensuring  that  the  public 
has  access  to  information  related  to  safety. 

It  is,  therefore,  proposed  that  in  no  case  may  the  following  information  be  kept 
confidential: 

the  characteristics  of  the  GMMs; 
name  and  address  of  the  notifier; 
location  of  use; 
level  and  measures  of  containment; 
the  evaluation  of  foreseeable  effects,  in  particular  any  harmful  effects  on  human 
health  and  the  environment. 

Article  20 

Given  the  pace  at  which  this  field  is  advancing  it  is  necessary  that  the  technical 
elements  of  the  Directive  (i.e.  the  Annexes)  are  easily  adaptable  to  technical  progress. 

The  Commission  considers  that  the  possibility  for  easy  adaptation  to  technical  progress 
should  also  be  introduced  for  Annex  I,  since  this  Annex  presents  the  technical 
interpretation  of  the  notion  described  in  Article  2(b)  and  as  such  it  should  reflect  the 
state  of  the  art. 

It  is,  therefore,  the  Commission's  proposal  that  all  Annexes  be  amendable  through  a 
Committee  procedure. 

Annex  I 

This  Annex  presents  a  technical  interpretation  of  the  term  "genetically  modified 
micro-organism"  as  defined  in  Article  2(b). 

Part  1 outlines the techniques  which  according  to recent  scientific  knowledge  fall  within 
the  notion  defined  in  Article  2(b),  while 

Part  2 outlines the techniques  which  according  to recent  scientific  knowledge  do not  fall 
within  the  abovementioned  notion. 

Annex  II 

Part  A:  This  part  of  the  Annex  has  been  adapted  to  technical  progress  and  outlines 
techniques  of  genetic  modification  which  should  be  excluded  from  the  scope  of  the 
Directive  in  accordance  with  Article  3. 

Part  B: This part  includes types  of  GMMs  which  are known  to be  safe  for  human  health 
and  the  environment,  and  which  are  excluded  from  the  Directive  in  accordance  with 
Article  3. 

The  Commission  has  at  present  been  able  to  identify  GMMs  known  to  be  safe,  which 
are  listed  in  Part  A  Given  the  pace  at  which  this  field  is  advancing  it  is  to  be  expected 
that  types  of  GMMs  known  to  be  safe  will  be  identified  in  the  future,  and  will  be 
included  in  Part  B. 

Annex  III 

This  Annex  outlines  the  principles  according  to  which  the  assessment  referred  to  in 
Article  5  should  be  carried  out. 

Paragraph  1  outlines  the  basic  elements  of  the  risk  assessment,  which  are:  the 
identification  of  potentially  harmful  effects,  their  severity  and  the- likelihood  of  them 
being  realized,  while  paragraph  2  outlines  the  effects  that  can  be  considered  as 
potentially  harmful. 

Paragraphs  3, 4  and  5 present  a harmonized  approach  to  the  categorization  of  activities 
and  selection  of  control  measures  based  on  already  existing  classification  schemes,  the 
new  properties  of  the  GMM,  the  characteristics  of  the  operation  and  the  characteristics 
of  the  environment  likely  to  be  exposed. 

Annex  IV 

In  order  to  ensure  harmonization  and  adequate  environmental  protection  it  has  been 
considered  necessary  to  further  specify  and  elaborate  upon  the  minimum  containment 
and  control  measures  for  each  risk  class  and  for  different  types  of  activities  following 
a  careful  examination  of  national  and  international  practices,  as  well  as  the  work  of 
CEN  in  this  field. 

The  result  of  this  analysis  has  been  Annex  IV,  which  presents  four  Tables  outlining 
minimum  containment  and  control  measures  for 
laboratory  activities  (Table  I  a, 
additional  measures  for  glasshouses  and  growthrooms  (Table  I  b  and  animal  units 
(Table  I  c,  as  well  as  minimum  containment  and  control  measures  for  other  than 
laboratory  activities  (Table  II). 

Annex  V 

This  Annex  outlines  the  information  which  should  be  submitted  for: 

the  first  time  that  activities  involving  GMMs  take  place  in  particular  premises 
(Part  A); 
Class  2  activities  in  particular  (Part  B); 
Class  3  and  Class  4  activities  in  particular  (Part  C) 

3. 

Impact  on  Small  and  Medium  Enterprises  (SMEs) 

The  Commission  estimates  that  the  proposed  amendment  will  have  a positive  impact  on 
small  and  medium  enterprises  and  their  competitiveness  for  the  following  reasons: 

• 

• 

• 

The  elimination  of  regulatory  redundancies  i.e.  administrative  requirements  not 
justified  by  safety,  will  have  a  positive  impact  on  the  competitiveness  of  SMEs. 

The  administrative  procedures  have  been  linked  to  the  actual  risk  of  the  activities 
following  a  classification  system  which  is  clear  and  compatible  with  other 
Community  legislation  (i.e.  Directive  90/679/EEC)  and  international  guidelines. 

The  proposed  classification  in  four  classes  of  risk  is expected  to  eliminate  current 
unnecessary  costs  for  the  management  of  low  risk  GMMs  which  currently  fall 
under  Group  II. 

The abolition of the non-risk  based and rather confusing  differential  treatment of 
operations for administrative purposes which currently places additional unjustified 
burdens on large scale and industrial operations without regard to actual risk leads 
to the direct linking of  administrative  burdens to the actual  risk  of activities and 
consequently  to rationalization  of  administrative costs. 

The administrative  procedures and requirements have been lightened for the vast 
majority  (Class  1 and Class 2) of activities  in which SMEs normally  engage, and 
have been brought closer to those currently  applied  by the main trading partners 
of  the  EU.  This  is  expected  to  lower  threshold  costs  for  SMEs  developing 
innovative  biotechnology  applications  and  could  provide  an incentive  for joint-
venture R&D investment  and for the location of  production  activities  in the EU. 

The provision of  clear guidance  as to the containment  and control  measures that 
should be  applied depending  on the risk of  the activities  and the clarification  of 
ambiguous technical terms is expected to contribute further to the reduction of the 
costs of compliance. 

Proposal  for a 
COUNCIL DIRECTIVE 
amending  Directive  90/219/EEC 
on the  contained  use of  genetically  modified  micro-organisms 

THE COUNCIL OF THE EUROPEAN UNION, 

Having  regard  to  the  Treaty  establishing  the  European  Community,  and  in  particular 
Article  130s  thereof, 

Having  regard to the proposal  from  the Commission, 

Acting  in  accordance  with  the  procedure  laid  down  in  Article  189c  of  the  Treaty,  in 
cooperation  with the European  Parliament, 

Having regard to the opinion  of  the Economic  and Social  Committee, 

Whereas, under the Treaty,  action by the Community  relating to the environment  should be 
based on the principle  that preventive  action  is to be taken and to  seek  to preserve,  protect 
and improve the environment  and to protect human health; 

Whereas  activities  involving  genetically  modified  micro-organisms  should  be  classified  in 
relation  to  the  risks  they  present;  whereas  such  classification  should  be  in  line  with 
international  practice;  whereas  such  classification  should  be  based on  an assessment  of  the 
risk; 

Whereas  appropriate  containment  and control  measures  should  be applied  to  ensure  a high 
level of safety; whereas the containment and control measures should be linked to the risk of 
the activities; 

the 

following  main  weaknesses  have  been 

Whereas 
in  Council 
Directive  90/219/EEC(1), as amended by Commission Directive 94/51/EC(2): the classification 
system is not in line with international practice, the administrative procedures and notification 
requirements  are not  linked  to  the  real risk of  activities;  the  administrative  procedures  for 
certain classes of activities involving genetically modified micro-organisms are unnecessarily 
restrictive;  there  is  insufficient  guidance  as  to  the  containment  and  control  measures 
which should  be  applied  in  order  to  protect  human  health  and  the  environment; 
Directive  90/219/EEC does not permit rapid adaptation to technical progress; technical parts 
of the Directive  need to be  adapted to technical progress; 

identified 

Whereas there is now considerable experience and knowledge of the risks associated with the 
contained  use of  genetically  modified  micro-organisms; 

Whereas Directive  90/219/EEC  should therefore  be amended  accordingly, 

HAS ADOPTED THIS DIRECTIVE: 

Directive  90/219/EEC  is hereby  amended  as follows: 

Article 1 

(1)  OJNoL  117,  8.5.1990,  p.  1. 
(2)  OJNo  L 297,  18.11.1994,  p. 29. 

10 

1.  Article  2  is amended  as follows: 

(a)  The  following  words  are  added  at the  end  of  paragraph  (a):  "including  viruses, 
viroids  and  animal  and  plant  cells  in  culture,  but  excluding  naked  nucleic  acid 
molecules"; 

(b) 

In paragraph (b), the references  to  "Annex I A" in subparagraphs  (i)  and (ii) are 
replaced by  "Annex I"; 

(c)  Paragraph (c)  is replaced by the following: 

"(c)  "contained  use"  shall  mean:  any  operation  in  which  micro-organisms  are 
genetically modified or in which such genetically  modified micro-organisms 
are cultured, stored, used, transported or destroyed  [deleted words],  and for 
which physical  barriers, or a combination of physical barriers together with 
chemical  and/or biological  barriers, are used to limit their contact  with the 
general population and the environment; or any activity in which genetically 
modified  micro-organisms  are disposed  of,  for  which physical  or chemical 
or biological  barriers, or any  combination  of  these types,  are used to  limit 
their contact  with the general  population  and the environment;" 

(d)  Paragraphs (d)  and (e)  are deleted; 

(e)  The following  paragraph  (i)  is added: 

"(i)  "significant  changes"  in  the  context  of  Article  6a(2)  shall  mean  changes 

which  could  change  the result of  the risk assessment." 

2.  Article  3 is  replaced by the  following: 

"Article 3 

This Directive  shall  not  apply  where genetic  modification  is obtained through the  use 
of the techniques or methods listed in Annex II, or for contained-use activities involving 
other types of genetically modified  micro-organisms known to be safe for human health 
and  the  environment.  Such  types  of  genetically  modified  micro-organisms  and  their 
characteristics  are listed  in Annex II, Part B"; 

3.  Article 4 is deleted. 

4.  Article  5 is amended  as follows: 

(a) 

In  the  first  sentence  the  words  "Articles  7  to  12"  are  replaced  by  the  words 
"Articles 6a and Articles  8 to 11"; 

(b)  The second  sentence  is  replaced by the  following: 

"This  Directive  shall  not  apply  to  the  storage,  culture,  transport,  destruction, 
disposal  or use of  genetically  modified  micro-organisms  which have been placed 
on  the  market  in  accordance  with  Directive  90/220/EEC  or  under  any  other 
Community 
legislation,  which  provides  for  a  specific  environmental-risk 
assessment  similar  to  that  laid  down  in  Directive  90/220/EEC,  provided  always 
that  the  contained  use  is  in  accordance  with  the  conditions,  if  any,  of  the 
marketing  approval  or consent." 

11 

5.  Article  6 is amended  as  follows: 

(a)  Paragraphs  2 and  3  are  replaced  by  the  following  texts: 

"2.  To  this end, the  user  shall  carry  out  an assessment  of the contained  uses as 
regards the risks to human health  and the environment  that they  may  incur, 
taking  due  account  of  the principles  set  out  in  Annex III. 

3.  The  assessment  should  result  in  the  categorization  of  the  contained-use 

activities  in  the  following  four  classes  of risk: 

Class  1 :  Activities  of  no, or  negligible,  risk,  that  is to  say,  activities  for 
which level  1  containment is appropriate to protect human health 
as  well  as  the  environment  that  could  be  exposed  to  the 
genetically  modified  micro-organisms. 

Class  2:  Activities  of  low  risk,  that  is  activities  for  which  level  2 
containment is appropriate to protect human health as well as the 
environment  that  could  be  exposed  to  the  genetically  modified 
micro-organisms  in the  absence  of  containment. 

Class  3:  Activities  of  moderate  risk,  that  is  activities  for  which  level  3 
containment is appropriate to protect human health as well as the 
environment  that  could  be  exposed  to  the  genetically  modified 
micro-organisms  in the  absence  of  containment. 

Class 4:  Activities  of  high  risk,  that  is  activities  for  which  level  4 
containment is appropriate to protect human health as well as the 
environment  that  could  be  exposed  to  the  genetically  modified 
micro-organisms  in the  absence  of  containment." 

(b) 

In  paragraph  4, the  words  "Articles  8,  9 and  10"  is replaced  by  the  words 
"Articles  8 and  10". 

6.  The  following  Article  6a  is  inserted: 

"Article  6a 

1. 

The  user  shall  apply  the  containment  and  control  measures  from  the  appropriate 
Table(s)  in  Annex  IV  corresponding  to  the  risk  class  of  the  activity,  so  as  to 
keep  workplace  and  environmental  exposure 
to  any  genetically  modified 
micro-organisms  to  the  lowest  reasonably  practicable  level,  and  so  that  a  high 
level  of  safety  is  ensured." 

2. 

The  risk  assessment  and  the  containment  and  control  measures  applied  shall  be 
periodically  reviewed  forthwith  if: 

(a) 

(b) 

there  has  been  a  significant  change  in  the  activity(ies)  to  which  the 
assessment  relates;  or 

there  is  reason  to  suspect  that  the  assessment  is  no  longer  adequate  as 
judged  in  the  light  of  new  scientific  or  technical  knowledge." 

7.  Article  7 is  deleted. 

12 

8.  Articles  8, 9 and  10 are replaced  by the  following: 

"Article 8 

When premises are to be used for the first time for activities involving the contained use 
of  genetically  modified  micro-organisms,  the  user  shall  be  required  to  submit  to  the 
competent  authorities  a  notification  containing  at  least  the  information  listed  in 
Annex V, Part A. 

Article 9 

For  Class  1 activities  to  be  carried  out,  no  further  notification  shall  be  needed.  Such 
activities shall be able to commence immediately  following  the notification  referred to 
in  Article  8. Users of  genetically  modified  micro-organisms  in Class  1 activities  shall 
be required to keep the record of each assessment referred to in Article 6(4), which shall 
be made available  to the competent  authority  on request. 

Article  10 

1. 

2. 

3. 

For  the  first  and  subsequent  Class  2  activities  to  be  carried  out  in  premises 
notified  in  accordance  with  Article  8,  a notification  containing  the  information 
listed in Annex V, Part B  shall  be submitted. 

If  no  previous  notification  has  been  submitted  for  Class  2  or  a higher  class  of 
activities, the contained use may, in absence of any indication to the contrary from 
the  competent  authority,  proceed  45  days  after  submission  of  the  notification 
referred to above, or earlier with the agreement of  the competent authority. 

If a previous notification  has been submitted for Class 2 activities or higher and 
the  associated  consent  requirements  have  been  satisfied,  the  contained  use may 
proceed immediately  following  the new notification." 

9.  The following  Article  10a is inserted: 

"Article  10a 

1. 

2. 

3. 

For first and subsequent Class 3 or Class 4 activities to be carried out in premises 
notified  in  accordance  with  Article  8,  a notification  containing  the  information 
listed in Annex V, Part C shall  be submitted. 

If  no  previous  notification  has  been  submitted  for  Class  3  or  a higher  class  of 
activities, the contained use may not proceed without the consent of the competent 
authority. The competent authority shall communicate its decision in writing at the 
latest  90 days after  submission  of the notification. 

If  a  previous  notification  has  been  submitted  for  Class  3  or  a higher  class  of 
activities  and  the  associated  consent  requirements  have  been  satisfied,  the 
contained use may in absence of any indication to the contrary from the competent 
authority proceed 45 days after submission of the new notification, or earlier with 
the agreement of  the  competent authority." 

10.  Article  11 is amended  as follows: 

(a)  The words "Article 8, Article 9(2) and Article  10" in paragraph  1 are replaced by 

the words  "Articles  8,  10 and 10a"; 

(b) 

In paragraph 2, the word "classification" is replaced by the words "risk  assessment 
and the class of risk"; 

13 

(c) 

In  point  (a)  of  paragraph  3,  the  second  sentence  is  replaced  by  the  following: 
"In this  case  the  competent  authority  may  require  that  the  contained  use,  if 
proposed, does not begin or, if in progress, is halted, until the competent authority 
has given  its approval  on the basis of  the further information  obtained  or of the 
modified  conditions  of  the  contained use"; 

(d)  Paragraphs 4 and 5 are deleted; 

(e) 

In  paragraph  6,  the  words  "paragraphs  4  and  5"  are  replaced  by  the  words 
"Articles  10 and 10a". 

11.  Paragraph  1 of  Article  12 is  replaced by the following: 

" 1. 

If the user becomes aware of relevant new information or modifies the contained 
use in a way which could have significant consequences for the risks posed by it, 
the competent authority shall be informed as soon as possible and the notification 
under Articles  8,  10 and  10a modified." 

12.  Article  13 is replaced by the  following: 

"Article 13 

Where a Member State considers it appropriate, it may provide that groups or the public 
shall  be  consulted  on  aspects  of  the  proposed  contained  use,  in  accordance  with 
Article  19." 

13.  Article  14 is replaced by the  following: 

"Article 14 

The  competent  authorities  shall  ensure  that,  where  necessary,  before  an  activity 
commences: 

(a)  An emergency  plan  is  drawn up for  Class 3 and Class 4  activities  where  failure 
of the containment measures could lead to serious danger, immediate or delayed, 
to humans outside the premises  and/or to the environment. 

(b) 

Information on emergency plans is supplied in an appropriate manner, and without 
their  having  to  request  it,  to  bodies  and authorities  liable  to  be  affected  by  the 
accident.  The information  shall  be  updated  at appropriate  intervals.  It  shall  also 
be made publicly  available. 

The  Member  States  concerned  shall  at  the  same  time  make  available  to  other 
Member States concerned, as a basis for all necessary consultation within the framework 
of their bilateral  relations, the  same information  as that which is disseminated  to their 
nationals." 

14.  Paragraph  1 of Article  15  is amended as follows: 

(a) 

In the second indent, the word "released" is replaced by the word "concerned"; 

(b) 

In the fourth  indent,  the  word  "emergency" is deleted. 

15. 

In point (b) of paragraph  1 of  Article  16, the phrase "the identity  and quantities of the 
genetically  modified  micro-organisms  released,  the  emergency  response  measures 
employed  and  their  effectiveness"  is  replaced  by  "the  identity  and  quantities  of  the 
genetically  modified  micro-organisms concerned, the response measures employed and 
their  effectiveness". 

14 

16 

In  Article  18,  paragraph  1 is  replaced  by  the  following: 

" 1.  Member  States  shall  send  to  the  Commission,  at  the  end  of  each  year,  a  summary 
report  on  the  Class  3  and  Class  4  contained  uses  notified  under  Article  10a, 
including  the  description,  purpose  and  risks  of  the  activity  or  activities." 

17. 

In  Article  19,  paragraph  4  is  replaced  by  the  following: 

"4. 

In no case may  the following  information,  when  submitted  according  to  Articles  8, 
9  or  10,  be  kept  confidential: 

the  characteristics  of  the  genetically  modified  micro-organisms,  name  and 
address  of  the  notifier,  and  location  of  use; 

the  level  and  measures  of  containment; 

the  evaluation  of  foreseeable  effects,  in  particular  any  harmful  effects  on 
human  health  and  the  environment." 

18. 

In  Article  20, the  words  "Annexes  II  to  V"  are  replaced  by  the  words  "Annexes  I to  V". 

19.  The  Annexes  are  amended  as  shown  in  the  Annex  hereto. 

Article  2 

1  Member  States shall  bring  into  force  the  laws, regulations  and  administrative  provisions 
necessary  to  comply  with  this Directive  by  1 January  1999.  They  shall  forthwith  inform 
the  Commission  thereof. 

When  Member  States  adopt  these  provisions,  these  shall  contain  a  reference  to  this 
Directive  or  shall  be  accompanied  by  such  reference  at  the  time  of  their  official 
publication.  The  procedure  for  such  reference  shall  be  adopted  by  Member  States. 

2.  Member  States  shall  communicate  to  the  Commission  the  text  of  the  main  provisions 

of  national  law  which  they  adopt  in  the  field  covered  by  this  Directive. 

Article  3 

This  Directive  shall  enter  into  force  on  the  twentieth  day  following  that  of  its  publication  in 
the  Official  Journal  of  the  European  Communities. 

This  Directive  is  addressed  to  the  Member  States. 

Article  4 

Done  at  Brussels, 

For  the  Council 
The  President 

15 

ANNEX 

The  Annexes  to  Directive  90/219/EEC  are  amended  as  follows: 

1. 

Former  Annex  I A becomes  Annex  I  and  is  amended  as  follows: 

(a) 

In  Part  1, point  (1) is  replaced  by  the  following: 

"(i) 

recombinant-nucleic  acid  techniques  involving  the  formation  of  new 
combinations  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 host  organism 
in  which  they  do  not  naturally  occur  but  in  which  they  are  capable  of 
continued  propagation." 

(b)  Part  2 is amended  as  follows: 

i 

(I) 

In  the  introductory  phrase,  the  word  "DNA"  is  replaced  by  the  words 
"nucleic  acid",  and the  following  words are added:  "made by  techniques  or 
methods  other  than  those  excluded  by  Annex II:" 

(ii)  Point  2 is replaced  by  the  following: 

"(2)  natural  processes  such  as: conjugation,  transduction,  transformation;" 

2.  Annex  I  B is  deleted. 

3 

Annex  II  is replaced  by  the  following: 

"Annex  II 

A.  Techniques  or  methods  of  genetic  modification  yielding  micro-organisms  to  be 
excluded  from  the  Directive  on  the  condition  that  they  do not  involve  the  use of 
recombinant-nucleic acid molecules or genetically modified micro-organisms other 
than  those  produced  by  one  or  more of  the techniques/methods  listed  below: 

1.  Mutagenesis; 

2. 

3. 

4. 

Cell fusion  (including protoplast fusion) of prokaryotic species that exchange 
genetic  material  by  known  physiological  processes,  where  the  resulting 
micro-organism  is  unlikely  to  cause  disease to  humans,  animals  or  plants; 

Cell fusion  (including  protoplast  fusion)  of cells of any  eukaryotic  species, 
including  production  of  hybridomas  and  plant  cell  fusions,  where  the 
resulting micro-organism  is unlikely  to cause disease to humans, animals or 
plants; 

Self-cloning  consisting in the removal  of nucleic acid sequences from  a cell 
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 
phytogenetically  closely related species which can exchange genetic material 
by  natural  physiological  processes,  where  the  resulting  micro-organism  is 
unlikely  to  cause  disease  to humans,  animals  or plants. 

16 

Self-cloning  may  include the use of  recombinant  vectors  with  an extended 
history of safe use in the particular micro-organisms. The following  are non-
exhaustive  examples of  safe  host/vector systems: 

E-coli  K  12 strains/pBR 322; 

Eukaryotic  cells/defective  Simian  virus 40  (SV 40). 

B.  Types of genetically  modified micro-organisms which have been shown to be safe 
for human health and the environment and which are, therefore, excluded from the 
Directive:" 

4.  Annex III is replaced  by the  following: 

"Annex III 

PRINCIPLES  TO  BE  FOLLOWED  FOR  THE  ASSESSMENT  REFERRED  TO  IN 
ARTICLE 6 

Elements of  assessment 

1.  The following  should be  considered  as potentially  harmful  effects: 

disease to humans,  animals or plants; 

adverse effects  resulting from the inability to treat disease or offer  effective 
prophylaxis; 

adverse  effects  resulting  from  establishment  or  dissemination  in  the 
environment; 

adverse effects  resulting  from transfer of genes to other organisms. 

2. 

a. 

The assessment  referred  to in Article 6 should be based on the  following: 

(i) 

the recipient  micro-organism; 

(ii) 

the inserted  (donated) genetic material; 

(iii)  the vector; 

(iv)  the donor micro-organism (if the donor micro-organism is used during 

the operation); 

(v) 

the resulting  genetically  modified  micro-organisms. 

The severity  of  the  potentially  harmful  effects. 

The likelihood  of  the potentially  harmful  effects  being realized. 

b. 

c. 

Procedure 

3. 

In order to  arrive  at the  categorization  of  a particular  activity,  as  referred  to  in 
Article 6, the user may take into consideration the risk class of the recipient, the 
vector  and,  if  applicable,  donor  micro-organism  as  given  in  other  Community 
legislation,  international  or national  schemes (e.g.  WHO, NIH etc.). 

i 

17 

These  classification  schemes  concern  natural  micro-organisms  and  are  usually 
based on  the ability  of  micro-organisms  to  cause  disease to humans  or animals, 
and  on  the  severity  and transmissibility  of  the  disease  likely  to  be  caused.  The 
user  may  also  take  into  consideration  classification  schemes  referring  to  plant 
pathogens (which are usually established on a national basis). The abovementioned 
classification  schemes  give  only  a provisional  indication  of  the  risk  class  of  the 
activity  and the corresponding  set of containment  and control measures required. 

4. 

The  final  classification  and  selection  of  control  measures  must  be  made  in  the 
light  of: 

(i) 

any  harmful  properties  (see  above)  which  the  vector "or inserted  material 
might  confer  on  the  recipient,  or  any  alteration  of  the  recipient's  existing 
properties; 

(ii) 

the characteristics  of  the operation (e.g.  its nature, scale); 

(iii)  the characteristics of the environment likely to be exposed to the genetically 
modified  micro-organisms  (e.g.  whether  in  the  environment  likely  to  be 
exposed to the genetically  modified  micro-organisms there are known biota 
which  can  be  adversely  affected  by  the  micro-organisms  used  in  the 
contained-use  activity). 

5. 

The  analysis  carried  out  as  described  under  paragraph  4  above  may  lead  to  a 
categorization of the risk of the activity higher or lower than the provisional  one. 
The check foreseen in paragraph 4 should be repeated, until the final  classification 
is stable." 

Annex IV  is replaced by the  following: 

"Annex IV 

Containment  and Control  Measures 

Preface 

These tables present the normal minimum requirements and measures necessary for each 
level  of  containment. 

Containment is achieved through the use of good workpractices, containment equipment 
and special  installation  design. 

The titles of the Tables  are indicative. 

Table I a presents minimum  requirements for laboratory  activities. 

I b  presents  additions 

Table 
for 
glasshouse/growthroom  activities  involving  genetically  modified  micro-organisms 
(GMMs). 

to  and  modifications  of  Table 

I a 

Table I c presents additions to and modifications of Table I a for activities with animals 
involving  genetically  modified  micro-organisms (GMMs). 

Table II presents minimum requirements for other activities than laboratories activities. 

In some particular cases, it might be necessary to apply a combination of measures from 
Table I a and Table II of  the same level. 

18 

In  some  exceptional  cases  (e.g.  for  plant  pathogens),  it  also  might  be  appropriate, 
following  consultation  with the Competent Authority  not to apply a specification  under 
a particular containment  level  or to  combine  specifications  from  two different  levels. 

In these Tables: 

* 

* 

noi 

means not required. 

optional: 

means that the  user should decide on a case-by-case  basis, subject 
to  the  risk  assessment,  to  what  extent  these  measures  are  to  be 
applied. 

* 

yes: 

means required. 

19 

Annex  IV 

Table  I a 

Containment  and  Control  Measures  for  Laboratory  Activities 

Specifications 

Containment  levels 

BUILDING 

Laboratory  suite:  isolation*" 

Laboratory:  sealable  for 
fumigation 

EQUIPMENT 

Surfaces  resistant  to  acids, 
alkalis,  solvents,  disinfectants 

Entry  to  lab  via  airlock(2) 

Negative  pressure  relative  to  the 
pressure  of  the  immediate 
surroundings 

Extract  and  input  air  from  the 
laboratory  should  be  HEPA-
filtered 

Microbiological  safety 
cabinet/enclosure 

1 

2 

3 

4 

5 

6 

7 

8 

1 

no 

no 

2 

no 

no 

3 

yes 

yes 

4 

yes 

yes 

yes(bench) 

yes  (bench) 

yes(bench, 
floor) 

optional 

yes 
except  for00 

yes(bench, 
floor,  ceiling, 
walls) 

yes 

yes 

yes  (HEPA)(3) 
-  Extract  air 
except  for(4) 

yes  (HEPA) 
-  Input  and 
extract  air 

no 

no 

no 

optional 

yes 

yes 

no 

no 

no 

no 

Autoclave 

on  site 

in the  building 

in  suite 

in  lab  =  double 
ended 

SYSTEM  OF  WORK 

9 

Restricted  access 

10 

11 

12 

Biohazard  signs on  the  door 

Control  of  aerosol  formation 

Washing  and  decontamination 
provisions  for  personnel 

no 

no 

no 

yes 

yes 

yes 

yes 
minimize 

yes 

yes 

yes 

yes 
prevent 

yes 

yes 

yes 

yes 
prevent 

yes 

(1) 

(2) 

0) 

(4) 

Isolation  = the laboratory  is separated  from  other areas in the same building or is in a separated  building. 
Airlock  =  Entry  must  be  through  an  airlock  which  is a chamber  isolated  from  the  laboratory. The clean  side  of  the  airlock 
must be separated  from  the restricted  side by changing or showering  facilities  and preferably  by interlocking doors. 
HEPA = High  Efficiency  Particulate Air. 
Activities where transmission  does not occur  via airborne route. 

20 

Containment  and  Control  Measures  for  Laboratory  Activities 

Specifications 

Containment  levels 

SYSTEM  OF  WORK 

13 

Shower 

1 

no 

2 

no 

14 

Protective  clothing 

labcoat 

labcoat 

3 

4 

optional 

yes 

suitable 
protective 
clothing  +  foot 
wear 

complete 
change  of 
clothing  +  foot 
wear  before 
entry  and  exit 

16 

17 

18 

19 

15 

Gloves 

Test  adequately  and  maintain 
control  measures  and  equipment 

Record  keeping 

no 

yes 

yes 

Efficient  vector  control  (e.g.  for 
rodents  and  insects) 

optional 

optional 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

W A S TE 

Inactivation  of  GMMs  in 
effluent  from  handwashing  sinks 
or  drains  and  showers  if  any 

no 

no 

optional 

yes 

20 

Inactivation  of  GMMs  in 
contaminated  material  and  waste 

optional 

yes 

yes 

yes 

21 

Annex IV 

Table  I  b 

Containment  and Control  Measures  for Glasshouses  and Growthrooms 

The terms glasshouse  and growthroom  refer to a structure with walls, a roof and a floor designed 
and used principally  for growing  plants  in a controlled and protected environment. 

All  provisions of Table I a shall  apply  with the following  additions/modifications: 

1 

2 

3 

4 

5 

6 

7 

Specifications 

Containment  levels 

BUILDING 

Greenhouse  : permanent 
structure0* 

EQUIPMENT 

Surroundings without 
susceptible plant species 

Entry via  a separated room 
with two interlocking doors 

1 

no 

no 

2 

yes 

optional 

optional 

optional 

3 

yes 

yes 

yes 

4 

yes 

yes 

yes 

Control of contaminated  run-off 
water 

optional 

minimize® run 
off 

prevent run- off 

prevent  run-off 

SYSTEM  OF  WORK 

Restricted access 

Measures to control undesired 
species as insects, rodents, 
arthropods 

Procedures for transfer  of living 
material between the 
glasshouse/growth  room, 
protective structure and 
laboratory  shall prevent 
dissemination  of  genetically 
modified  microorganisms 

yes (visitors 
accepted) 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

minimize 
dissemination 

minimize 
dissemination 

prevent 
dissemination 

prevent 
dissemination 

(5) 

(6) 

The  glasshouse  shall  consist  of  a  permanent  structure  with  a  continuous  waterproofed  covering,  located  on  a  site  graded  to 
prevent  entry  of  surface  runoff  having  self-closing  lockable  doors. 
Where  transmission  can  occur  through  the  ground. 

22 

Annex  IV 

Table  I c 

Containment  and  Control  Measures  for  Activities  in  Animal  Units 

All  provisions  of  Table  I  a shall  apply  with  the  following  additions/modifications: 

Specifications 

Containment  levels 

1 

2 

3 

4 

5 

FACILITIES 

Isolation  of  animal  unit(7) 

Animal  facilities(8)  separated  by 
lockable  doors 

Animal  facilities  design  for 
decontamination  (waterproof 
and  easily  washable  material 
(cages,  etc.)) 

Floor  and/or  walls  easily 
washable 

Animal  containment  in 
appropriate  cages,  pens  or 
tanks 

6 

Filters  on  isolators(9) 

1 

optional 

yes 

optional 

i 

2 

yes 

yes 

optional 

3 

yes 

yes 

yes 

4 

yes 

yes 

yes 

yes  (floor) 

yes  (floor) 

yes  (floor  and 
walls) 

yes  (floor  and 
walls) 

yes 

no 

yes 

yes 

yes 

no 

optional 

yes 

(7) 

(8) 

(9) 

Animal  unit:  a  building,  or  separate  area  within  a  building  containing  facilities  and  other  areas  such  as  changing  rooms,  showers, 
autoclaves,  food  storage  areas  etc. 
Animal  facility:  a  facility  normally  used  to  house  stock,  breeding  or  experimental  animals  or one  which  is used  for  the  performance  of 
minor  surgical  procedures. 
isolators:  transparent  boxes  where  the  animal  is  contained  within  or  outside  a  cage. 

23 

Annex  IV 

Table II 

Containment  and  Control  Measures for  other  Activities 

Specifications 

GENERAL 

1 

Viable  micro-organisms  should  be  contained  in  a  system 
which  physically  separates  the  process  from  the  environment 
(closed  system) 

2 

Control  of  exhaust  gases  from  the  closed  system 

Control  of  aerosols  during  sampling  collection,  addition  of 
material  to  a  closed  system  or  transfer  of  material  to  another 
closed  system 

Inactivation  of  bulk  culture  fluids  before  removal  from  the 
closed  system 

3 

4 

5 

6 

1 

no 

no 

no 

no 

Containment  levels 

2 

3 

4 

yes 

yes 

yes 

yes, 
minimize 
release 

yes, 
minimize 
release 

yes,  by 
validated 
means 

minimize 
release 

yes, 
prevent 
release 

yes, 
prevent 
release 

yes,  by 
validated 
means 

prevent 
release 

yes, 
prevent 
release 

yes, 
prevent 
release 

yes,  by 
validated 
means 

prevent 
release 

Seals  should  be  designed  so  as  to  minimize  or  prevent 
release 

no 
specific 
requirement 

The  controlled  area  should  be  designed  to  contain  spillage  of 
the entire  contents  of  the  closed  system 

optional 

optional 

yes 

yes 

7 

The  controlled  area  should  be  sea lab le  to  permit  fumigation 

no 

no 

optional 

yes 

8 

9 

10 

11 

12 

EQUIPMENT 

Entry  via  airlock 

no 

no 

optional 

yes 

Surfaces  resistant  to  acids, alkalis,  solvents,  disinfectants 

optional 

optional 

yes 
(bench  if 
any,  floor) 

yes 
(bench, 
floor, 
ceiling, 
walls) 

The  controlled  area  should  be  adequately  ventilated  to 
minimize  air  contamination. 

optional 

optional 

optional 

yes 

The  controlled  area  should  be  maintained  at  an  air  pressure 
negative  to  the  immediate  surroundings 

Extract  and  input  air  from  the  controlled  area  should  be 
HEPA  filtered 

no 

no 

no 

no 

optional 

yes 

yes  (input 
and 
extract 
air) 

yes 
(extract 
air, 
optional 
for  input 
air) 

24 

Containment  and  Control  Measures  for  other  Activities 

Specifications 

Containment  levels 

SYSTEM  OF  W O RK 

13 

14 

Closed  systems  should  be  located  within  a  controlled  area 

Access  should  be  restricted  to  nominated  personnel  only 

15 

Biohazard  signs  should  be  posted 

16 

17 

18 

Washing  and  decontamination  provisions  for  personnel 

Personnel  should  shower  before  leaving  the  controlled  area 

Personnel  should  wear  protective  clothing 

1 

no 

no 

no 

yes 

no 

2 

optional 

yes 

yes 

yes 

no 

yes  (work 
clothing) 

yes  (work 
clothing) 

3 

yes 

yes 

yes 

yes 

optional 

yes 

19 

Test  adequately  and  maintain  control  measures  and 
equipment 

20 

Record  keeping 

21 

Appropriate  training  and  supervision  for  personnel 

W A S TE 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

4 

yes 

yes 

yes 

yes 

yes 

complete 
change 
before 
exit  and 
entry 

yes 

yes 

yes 

22 

23 

24 

Inactivation  of  GMMs  in  effluent  from  handwashing  sinks 
and  showers  if  any 

no 

no 

optional 

yes 

Inactivation  of  GMMs  in  contaminated  material  and  waste 

optional 

yes 

yes 

yes 

Inactivation  of  GMMs  in  process  effluent  before  fmal 
discharge 

optional 

yes,  by 
validated 
means 

yes,  by 
validated 
means 

yes,  by 
validated 
means 

25 

6.  Annex  V  is  replaced  by  the  following: 

"Annex V 

PART A 

Information  required  for  the  notification  referred  to  in  Article  8: 

name of user(s) including those responsible for supervision and safety  information 
on  their  training  and  qualifications; 
details  of  any  biological  committees  or  subcommittees; 
address  of  installation; 
general  description  of  the  premises; 
a  description  of  the  nature  of  the  work  which  will  be  undertaken; 
the  class of  risk  of  the  activities; 
a  summary  of  the  risk  assessment  referred  to  in  Article  6(2)  and  (3)  (only  for 
Class  1 activities). 

PARTB 

Information  required  for  the  notification  referred  to  in  Article  10: 

the  date of  submission  of  the  notification  referred  to  in Article  8; 
the recipient, donor and/or parental micro-organism(s) used and, where applicable, 
the host-vector  system(s)  used; 
the source(s) and the intended function(s)  of the genetic material(s) involved in the 
manipulation(s); 
identity  and  characteristics  of  the genetically  modified  micro-organism(s); 
the  purpose  of  the  contained  use  including  the expected  results; 
approximate  culture  volumes  to be  used; 
description  of  the  containment  and  control  measures  to  be  applied,  including 
information  about  the  wastes  to  be generated,  their  treatment,  ultimate  form  and 
destination; 
a  summary  of  the  risk  assessment  referred  to  in  Article  6(2)  and (3). 

PART C 

Information  required  for  the  notification  referred  to  in  Article  10a: 

(a) 

- 

(b) 

- 

(c) 

- 

the  date of  submission  of  the notification  referred  to  in  Article  8; 
name  of  the  responsible  person; 

the  recipient  or  parental  micro-organism(s)  to be  used; 
the host-vector  system(s)  to  be  used  (where  applicable); 
the source(s)  and  intended  function(s)  of the genetic material(s) involved  in 
the  manipulation(s); 
identity  and  characteristics  of the  genetically  modified  micro-organism; 
the  culture  volumes  to  be  used; 

description of the containment and control measures to be applied, including 
information  about  the  type  and  form  of  wastes  to  be  generated,  their 
treatment,  ultimate  form  and  destination; 
the purpose  of  the  contained  use including  the  expected  results; 
description  of  the  sections  of the  installation; 

26 

(d) 

information  about  accident  prevention  and  emergency  response  plans,  if  any: 

the  sources  of  hazards  and conditions  under  which  accidents  might  occur; 
any  specific  hazards  arising  from  the  location  of the  installation; 
the  preventive  measures  applied  such  as  safety  equipment,  alarm  systems 
and  containment  methods; 
procedures  and  plans  for  verifying  the  continuing  effectiveness  of  the 
containment  measures; 
a  description  of  information  provided  to  workers; 
the  information  necessary  for  the  Competent  Authority  to  evaluate  any 
emergency  response  plans  prepared  in  accordance  with  Article  14; 

(e) 

a copy  of  the  risk  assessment  referred  to  in  Article  6(2)  and (3). 

27 

CONSOLIDATED  TEXT  WITH AMENDMENTS  UNDERLINED 

ANNEX 

ARTICLE  1 

This Directive lays down common  measures for the contained  use of genetically  modified  micro 
organisms with a view to protecting human health and the environment. 

ARTICLE  2 

For the purposes of this Directive: 

(a) 

(b) 

'micro-organism' shall  mean  any  microbiological  entity,  cellular or non-cellular,  capable 
of replication or of transferring  genetic  material; including viruses, viroids.  animal and 
plant cells in culture, but excluding naked nucleic  acid molecules. 

'genetically  modified  micro-organism' (GMM)  shall  mean a micro-organism  in which the 
genetic material  has been  altered  in a way that does not occur naturally by mating and/or 
natural recombination. 

Within the terms of this definition: 

(i) 

(ii) 

genetic  modification  occurs at least through the use of the techniques listed in 
Annex I. Part 1; 
the techniques listed  in Annex I. Part 2,  are not considered  to result in genetic 
modification; 

'contained use' shall  mean  any  activity  in which micro-organisms  are genetically 
modified  or in which  such genetically  modified  micro-organisms  are cultured, stored, 
used, transported, destroyed and for  which physical  barriers, or a combination of physical 
barriers together with chemical  and/or biological  barriers, are used to limit their contact 
with the general  population  and the environment; or any  activity  in which GMMs are 
disposed of and for which  physical  or chemical  or biological  barriers or any  combination 
of these types are used to  limit their contact with the general population  and the 
environment. 

'accident' shall  mean any  incident  involving  a significant  and unintended release of 
genetically  modified  micro-organisms  in the course of their contained use which  could 
present an immediate or delayed hazard to human health or the environment; 

'user' shall  mean any natural  or legal  person responsible  for the contained  use of 
genetically  modified  micro-organisms; 

'notification'  shall  mean the presentation of the requisite information  to the competent 
authorities of  a Member State. 

'significant  changes' in the context of  Article 6 (2) shall  mean changes which could 
change the result of the risk  assessment: 

(c) 

(d) 

(e) 

(f) 

(g) 

28 

ARTICLE  3 

This  Directive  shall  not  apply  where  genetic  modification  is  obtained  through  the  use  of  the 
techniques/methods  listed  in  Annex  IL  or  for  contained  use  activities  involving  other  types  of 
GMMs known  to  be  safe  for human  health  and the  environment.  Such  types of  GMMs and their 
characteristics shall  be listed  in  Annex  IL part B. 

ARTICLE  4 

Articles 6 to  11 shall not apply to the transport of genetically  modified  micro-organisms by 
road, rail, inland waterway, sea or air. This Directive shall not apply to the storage, culture, 
transport, destruction, disposal  or use of  genetically  modified  micro-organisms which have 
been  placed  on  the  market  in  accordance  with  Directive  90/220/EEC  or  under  other 
Community legislation, which provides for a specific  environmental risk assessment similar 
to that laid down in Directive  90/220/EEC. provided that the contained use is in accordance 
with the conditions,  if  any, of  the marketing approval/consent. 

ARTICLE  5 

1. 

2. 

3. 

Member States shall ensure that all appropriate measures are taken to avoid adverse  effects 
on  human  health  and  the  environment  which  might  arise  from  the  contained  use  of 
genetically  modified  micro-organisms. 

To this end the user shall  carry out an assessment of the contained uses as regards the  risks 
to  human  health  and  the  environment  that  they  may  incur,  taking  due  account  of  the 
principles set out in Annex III. 

Such  an assessment  should  result  in  the categorisation  of  the  contained  use activities  in 4 
classes of risk: 

Class  1: 

Class 2: 

Class 3: 

Class 4: 

Activities  of  no  or  negligible  risk,  that  is  activities  for  which  level  1 
containment is appropriate to protect human health as well as the environment 
that could be  exposed  to the GMMs in the absence of containment. 
Activities  of  low  risk,  that  is  activities  for  which  level  2  containment  is 
appropriate to protect human health as well  as the environment that could be 
exposed to  the GMMs in the absence of containment. 
Activities of moderate risk, that is activities for which level 3 containment is 
appropriate to protect human health as well  as the environment that could be 
exposed to the  GMMs in the absence of containment-
Activities  of  high  risk,  that  is  activities  for  which  level  4  containment  is 
appropriate to protect human health as well as the environment that could be 
exposed  to the  GMMs in the absence of containment. 

4. 

A record of this assessment  shall  be kept by the user and made available in an appropriate 
form  to  the competent  authority  as part of the notification  under Articles  7 and 9 or upon 
request 

29 

ARTICLE  6 

5. 

6. 

The user shall apply the containment and control measures from the appropriate Table(s) in 
Annex  IV  corresponding  to  the  risk  class  of  the  activity,  so  as  to  keep  workplace  and 
environmental  exposure  to  any  genetically  modified  micro-organisms  to  the  lowest 
reasonably  practicable  level,  and so that a high  level  of safety  is ensured. 

The risk assessment and the containment and control measures applied shall be periodically 
reviewed forthwith  if: 

a. 

b. 

there has been a significant change in the activitv(ies) to which the assessment relates 
or 
there is reason to suspect that the assessment is no longer adequate as judged in the 
light of new scientific  or technical  knowledge 

ARTICLE  7 

When  premises  are  to  be  used  for  the  first  time  for  activities  involving  the  contained  use  of 
genetically  modified  micro-organisms,  the  user  shall  be  required  to  submit  to  the  competent 
authorities a notification  containing  at least the information  listed in Annex VA. 

ARTICLE  8 

For class  1 activities to be carried out no further notification  shall be needed.  Such activities shall 
be  able  to  commence  immediately  following  the  notification  referred  to  in  Article  7.  Users  of 
genetically  modified  micro-organisms  in class  1 activities  shall  be required to  keep the  record of 
each  assessment  referred  to  in  Article  5  (4).  which  shall  be  made  available  to  the  competent 
authority on request. 

ARTICLE  9 

1. 

2. 

3. 

For first and subsequent class 2 activities to be carried out in premises notified in accordance 
with  Article  7.  a  notification  containing  the  information  listed  in  Annex  VB  shall  be 
submitted. 

If  no  previous  notification  has  been  submitted  for  that  or  higher  class  of  activities,  the 
contained  use  may,  in  absence  of  any  indication  to  the  contrary  from  the  competent 
authority, proceed 45  days after  submission  of the notification  referred to above,  or earlier 
with the agreement of the competent authority. 

If  a  previous  notification  has  been  submitted  for  class  2  activities  or  higher  and  the 
associated  consent  requirements  have  been  satisfied,  the  contained  use  may  proceed 
immediately  following  the new  notification. 

30 

ARTICLE  10 

1. 

2. 

3. 

For first and subsequent  class  3 or class 4  activities  to  be  carried  out  in premises  notified 
in accordance  with Article  7. a notification  containing the information  listed  in Annex VC 
shall  be submitted. 

If  no  previous  notification  has  been  submitted  for  that  or  higher  class  of  activities,  the 
contained  use  may  not  proceed  without  the  consent  of  the  competent  authority.  The 
competent  authority  shall  communicate  its  decision  in  writing  at the  latest  90  davs  after 
submission  of the notification. 

If a previous notification  has been  submitted for the same or higher class of  activities and 
the associated  consent  requirements have been  satisfied,  the contained  use may  in absence 
of  any  indication  to  the  contrary  from  the  competent  authority  proceed  45  davs  after 
submission of the new notification, or earlier with the agreement of the  competent authority. 

ARTICLE  11 

1. 

2. 

Member  States  shall  designate  the  authority  or  authorities  competent  to  implement  the 
measures which they adopt in application of this Directive and to receive and acknowledge 
the notifications  referred to  in  Article  7.  Article 9 and Article 10. 

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 risk assessment and the class of risk and, where appropriate, the adequacy 
of the waste management,  safety,  and emergency  response measures. 

3. 

If necessary, the competent  authority may: 

a. 

ask  the  user  to  provide  further  information  or  to  modify  the  conditions  of  the 
proposed contained use or to amend the class of risk assigned to the activity(ies). In 
this case the competent authority may require that the contained use, if proposed does 
not  begin,  or  if  in  progress  is  halted,  until  the  competent  authority  has  given  its 
approval  on  the  basis  of  the  further  information  obtained  or  of  the  modified 
conditions of the contained use; 

b. 

limit the time for which the contained use should be permitted or subject it to certain 
specific  conditions. 

4. 

For the purpose of calculating the periods referred to in Article 9 and Article  10. any periods 
of time during which the competent authority: 

is awaiting any further information  which it may have requested from the notifier in 
accordance  with paragraph  3 (a) or 

is  carrying out a public  inquiry or consultation  in accordance with Article  13 

shall  not be taken into account. 

31 

ARTICLE  12 

1. 

2. 

If the user becomes  aware of  relevant  new information  or modifies  the contained  use  in a 
way  which  could  have  significant  consequences  for  the  risks  posed  by  it,  the  competent 
authority shall be informed  as soon  as possible and the notification  under Article  7^ Article 
9  and Article  10 modified. 

If information becomes available subsequently to the competent authority which could have 
significant  consequences for  the  risks posed by the  contained  use, the competent  authority 
may require the user to modify  the conditions of,  suspend or terminate the contained use. 

ARTICLE  13 

Where a Member State considers  it  appropriate,  it may  provide that the public  shall  be  consulted 
on  aspects of the proposed contained  use in accordance with  Article  19. 

ARTICLE  14 

The competent authorities shall  ensure that, where necessary,  before  an activity commences: 

(a) 

(b) 

An  emergency  plan  is  drawn  up  for  class  3  and  class  4  activities  where  failure  of  the 
containment measures could lead to serious danger; immediate or delayed, to humans outside 
the premises and/or to the environment. 

Information  on  emergency  plans  is  supplied  in  an  appropriate  manner,  and  without  their 
having  to  request  it.  to  bodies  and  authorities  liable  to  be  affected  by  the  accident.  The 
information shall be updated at appropriate intervals. It shall also be made publicly available. 

The  Member  States  concerned  shall  at  the  same  time  make  available  to  other  Member  States 
concerned, as a basis for all necessary  consultation within the framewoik of their bilateral relations, 
the same information  as that which  is  disseminated to their nationals. 

ARTICLE  15 

1. 

Member States shall take the necessary  measures to ensure that, in the event of an accident, 
the user shall be required immediately to inform the competent authority specified  in Article 
11 and provide the following  information. 

the circumstances of  the accident, 
the identity  and quantities of  the genetically  modified  micro-organisms concerned, 
any  information  necessary  to  assess the effects  of  the accident  on the health  of  the 
general  population  and the environment, 
the measures taken. 

2.  Where information  is given  under paragraph  1, the Member States shall  be required to: 

32 

ensure  that  any  medium  and  long-term  measures  necessary  are  taken,  and 
immediately  alert any  Member  State which  could be affected  by the accident; 
collect, where possible, the information  necessary  for a full  analysis of the accident 
and,  where  appropriate,  make  recommendations  to  avoid  similar  accidents  in  the 
future  and to limit  the effects  thereof. 

ARTICLE  16 

1. 

Member States shall  be required to: 

(a) 

(b) 

consult with other Member States likely to be affected  in the event of an accident in 
the implementation  of  emergency plans; 
inform the Commission  as soon as possible of any accident within the scope of this 
Directive,  giving  details  of  the  circumstances  of  the  accident,  the  identity  and 
quantities of the genetically modified micro-organisms concerned, the measures taken 
and their effectiveness,  and an analysis of  the  accident  including  recommendations 
to limit its effects  and avoid  similar accidents in the future. 

2. 

The Commission, in consultation with the Member States, shall establish a procedure for the 
exchange of information  under paragraph  1. It shall  also set up and keep at the disposal  of 
the Member  States  a register  of  accidents  within  the scope  of this Directive,  including an 
analysis  of  the  causes  of  the  accidents,  experience  gained  and  measures  taken  to  avoid 
similar accidents in the future. 

ARTICLE  17 

Member  States  shall  ensure  that  the  competent  authority  organizes  inspections  and  other control 
measures to ensure user compliance  with this Directive. 

ARTICLE  18 

1. 

2. 

3. 

4. 

Member States shall send to the Commission, at the end of each year, a summary report on 
class  3  and  class  4  contained  uses  notified  under  Article  10  including  the  description, 
purpose and risks of  the activitv(ies). 

Every  three years,  Member  States  shall  send  the  Commission  a summary  report  on  their 
experience  with this Directive,  the first time being  on 

Every three years, the Commission shall publish a summary based on the reports referred to 
in paragraph 2, the first time being  in 

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 position  of  a user. 

33 

ARTICLE  19 

1. 

2. 

3. 

4. 

The  Commission  and  the  competent  authorities  shall  not  divulge  to  third  parties  any 
confidential  information notified or otherwise provided under this Directive and shall protect 
intellectual  property rights relating  to the data received. 

The notifier may indicate the information in the notifications submitted under this Directive, 
the  disclosure  of  which  might  harm  his  competitive  position,  that  should  be  treated  as 
confidential.  Verifiable justification  must be given  in such cases. 

The competent authority shall decide, after consultation with the notifier, which information 
will  be kept confidential  and shall  inform  the notifier  of  its decision. 

In no case may the following  information,  when submitted according to Articles 7,  8. or 9. 
be kept confidential: 

the characteristics of the genetically modified micro-organisms, name and address of 
the notifier,  and location  of use; 
level  and measures of  containment; 
the  evaluation  of  foreseeable  effects  in  particular  any  harmful  effects  on  human 
health and the environment. 

5. 

If, for whatever reasons, the notifier withdraws the notification, the competent authority must 
respect the confidentiality  of  the information supplied. 

ARTICLE  20 

Amendments necessary to adapt Annexes I to V to technical progress shall be decided in accordance 
with the procedure defined  in Article 21. 

ARTICLE  21 

1. 

2. 

The  Commission  shall  be  assisted  by  a committee  composed  of  the  representatives  of  the 
Member States and chaired by the representative  of the Commission. 

The representative of the Commission  shall submit to the committee a draft of the measures 
to be taken. The committee shall  deliver  its opinion  on the draft  within  a time  limit which 
the chairman  may  lay  down  according  to  the  urgency  of  the matter.  The  opinion  shall  be 
delivered by the majority  laid down in Article  148 (2) of the Treaty in the case of decisions 
which the Council is required to adopt on a proposal from the Commission. The votes of the 
representatives of the Member States within the committee shall be weighted in the manner 
set out in that Article.  The chairman shall  not vote. 

3. 

(a) 

(b) 

The Commission  shall  adopt the measures envisaged  if  they are in accordance with 
the opinion of the committee, 
If the measures envisaged  are not in accordance with the opinion of the committee, 
or  if  no  opinion  is  delivered,  the  Commission  shall,  without  delay,  submit  to  the 

34 

Council  a proposal  relating  to the measures to be taken. The Council  shall  act by a 
qualified  majority. 

If,  on the expiry of a period of three months from the date of referral  to the Council, 
the  Council  has  not  acted,  the  proposed  measures  shall  be  adopted  by  the 
Commission,  save  where  the  Council  has  decided  against  the  said  measures  by  a 
simple majority. 

ARTICLE  22 

Member States shall  bring  into force  the  laws, regulations and administrative provisions 
necessary  to comply  with this Directive  not later than 
Commission  thereof. 

They  shall  forthwith  inform  the 

ARTICLE  23 

This Directive  is addressed to the Member States. 

35 

ANNEX  I 

PART  I 

Techniques of  genetic  modification  referred  to in  Article  2 (b)  (1) are, inter alia: 

(i) 

(ii) 

(iii) 

recombinant nucleic acid techniques involving the formation of new combinations of genetic 
material bv 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  host  organism  in  which  thev  do  not  naturally  occur  but  in  which  they  are  capable  of 
continued propagation. 

techniques  involving  the  direct  introduction  into  a  micro-organism  of  heritable  material 
prepared outside the micro-organism  including micro-injection, macro-injection  and micro 
encapsulation; 

cell  fusion  or hybridization  techniques where live  cells  with new combinations of heritable 
genetic  material  are formed  through the  fusion  of two  or more  cells  by means of  methods 
that do not occur naturally. 

PART  2 

Techniques referred to in Article 2 (b) (ii) which are not considered to result in genetic  modification, 
on condition that they  do not involve the use of recombinant-nucleic  acid molecules or genetically 
modified  micro-organisms  made bv techniques/methods  other than those  excluded  bv  Annex II: 

(1) 
(2) 
(3) 

in vitro fertilization; 
natural processes  such  as: conjugation,  transduction,  transformation; 
polyploidy  induction. 

36 

ANNEX  II 

A. 

1. 

2. 

3. 

4. 

Techniques/methods  of genetic  modification  yielding  micro-organisms to be excluded from 
the Directive  on the condition  that they do not involve the use of  recombinant-nucleic  acid 
molecules  or GMMs other than those  produced bv one  or more of the  techniques/methods 
listed below: 

Mutagenesis. 

Cell fusion (including protoplast fusion) of prokarvotic species that exchange genetic material 
by known physiological  processes, where the resulting  micro-organism  is unlikely  to cause 
disease  to humans, animals or plants. 

(including  protoplast  fusion)  of  cells  of  any  eukaryotic  species,  including 
Cell  fusion 
production  of  hvbridomas  and  plant  cell  fusions,  where  the  resulting  micro-organism  is 
unlikely  to cause  disease to humans, animals or plants. 

Self-cloning  consisting in the removal of nucleic acid sequences from a cell of an organism 
which  may  or may  not be  followed  bv  reinsertion  of  all  or part of  that nucleic  acid  (or a 
synthetic  equivalent)  with  or without  prior enzvmic  or mechanical  steps - into cells  of the 
same  species  or into  cells  of  phvtogeneticallv  closely  related  species  which  can  exchange 
genetic  material  bv natural  physiological  processes,  where the resulting  micro-organism  is 
unlikely  to cause  disease to humans, animals or plants. 

Self-cloning  may include the use of recombinant vectors with an extended history of safe use 
in  the  particular  micro-organisms.  The  following  are  non-exhaustive  examples  of  safe 
host/vector systems: 

E-coli  K  12 strains/pBR  322 
Eukaryotic  cells/defective  Simian virus 40  (SV  40) 

B. 

Types of  GMMs which  have been shown to be safe for human health and the environment 
and which  are excluded  from  the Directive: 

37 

(Completiy  new  text) 

ANNEX  III 

PRINCIPLES  TO BE  FOLLOWED  FOR  THE ASSESSMENT  REFERRED  TO  IN  ARTICLE  S 

Elements of  assessment 

1. 

The following  should be considered  as potentially  harmful  effects: 

disease to humans, animals or plants; 
adverse  effects  resulting  from  the inability  to treat disease or offer  effective 
prophylaxis; 
adverse  effects  resulting  from  establishment  or dissemination  in the 
environment; 
adverse  effects  resulting  from  transfer of  genes to other organisms. 

2. 

The assessment  referred to in  Article  5 should be based on the  following: 

a) 

The identification  of  any  potentially  harmful  effects  of  the operation,  in particular 
any potentially  harmful  effects  associated with: 

i) 
ii) 
iii) 
iv) 

v) 

the recipient  micro-organism 
the inserted (donated)  genetic material 
the vector 
the donor micro-organism  (if the donor micro-organism  is used during the 
operation) 
the resulting GMM 

The severity  of  the potentially  harmful  effects 

The likelihood of the potentially  harmful  effects  being realised. 

b) 

c) 

Procedure 

In order to arrive at the categorisation  of  a particular activity;  as referred  to in  Article  5, 
the user may take into  consideration  the risk  class of  the recipient, the vector  and, if 
applicable,  donor micro-organism  as given  in other Community  legislation,  international 
or national  schemes (e.  g.  WHO, NTH etc.). 
These classification  schemes  concern natural micro-organisms  and are usually  based on 
the ability  of  micro-organisms  to  cause  disease to humans or animals, and on the severity 
and transmissibility of  the disease  likely  to be caused.  The user may  also take into 
consideration  classification  schemes referring  to plant pathogens  (which  are usually 
established on a national  basis).  The above  mentioned  classification  schemes  give  only a 
provisional  indication  of  the risk  class of  the activity  and the corresponding  set of 
containment  and control  measures required. 

The final classification  and selection  of  control  measures  must be made in the light  of: 

38 

i) 

11) 
iii) 

any harmful  properties  (see  above)  which  the  vector or inserted material 
might  confer  on the recipient,  or any  alteration  of the recipient's  existing 
properties; 
the characteristics  of the operation  (e.  g.  its nature, scale); 
the characteristics  of  the environment  likely  to be exposed  to the GMMs 
(e.  g.  whether  in the environment  likely  to be exposed  to the GMMs there 
are known biota  which  can be adversely  affected  by the  micro-organisms 
used in the  contained  use activity). 

The analysis  carried out as described  under para. 4 above  may  lead to a categorisation  of 
the risk  of  the activity  higher or lower than the provisional  one.  The check  foreseen  in 
para. 4 should be repeated,  until  the final classification  is stable. 

39 

(New  text  and  Tables) 

ANNEX 

IV 

Containment and Control Measures 

Preface 

These  tables  present  the  normal  minimum  requirements  and  measures  necessary  for  each  level  of 
containment. 

Containment  is  achieved  through  the  use  of  good  workpractices,  containment  equipment  and  special 
installation design. 

The titles of  the Tables are indicative. 
Table la presents minimum  requirements  for laboratory activities. 
Table lb presents additions to and modifications  of Table la for glasshouse/growthroom  activities  involving 
genetically  modified  micro-organisms  (GMMs). 
Table Ic presents additions to and modifications  of Table la for activities with  animals  involving  genetically 
modified  micro-organisms  (GMMs). 

Table II presents minimum  requirements  for other activities  than laboratories  activities. 

In some particular cases, it might be necessary  to apply  a combination  of  measures  from  table  I a and  table 
II of the same level. 

In some exceptional cases (e. g. for plant pathogens), it also might be appropriate, following  consultation with 
the  Competent  Authority  not  to  apply  a specification  under  a particular  containment  level  or  to  combine 
specifications from two different  levels. 

In these Tables: 

no: 
optional: 

yes: 

means not required 
means  that the user should  decide on  a case  by  case  basis, subject  to  the 
risk assessment,  to what extent  these  measures  are to be  applied. 
means required 

40 

Annex IV 
Table  I a 
Containment and Control  Measures  for Laboratory  Activities 

Specifications 

Containment  levels 

BUILDING 

Laboratory  suite:  isolation(1) 

Laboratory:  sealable  for 
fumigation 

EQUIPMENT 

1 

no 

no 

2 

no 

no 

3 

yes 

yes 

4 

yes 

yes 

Surfaces  resistant  to  acids, 
alkalis,  solvents,  disinfectants 

yes(bench) 

yes  (bench) 

Entry  to  lab  via  airlock(2) 

Negative  pressure  relative  to  the 
pressure  of  the  immediate 
surroundings 

Extract  and  input  air  from  the 
laboratory  should  be  HEPA-
filtered 

Microbiological  safety 
cabinet/enclosure 

no 

no 

no 

no 

yes(bench, 
floor) 

optional 

yes 
except  for 

yes  (bench, 
floor,  ceiling, 
walls) 

yes 

yes 

yes  (HEPA)(Î) 
-  Extract  air 
except  for(4) 

yes  (HEPA) 
-  Input  and 
extract  air 

no 

no 

no 

optional 

yes 

yes 

1 

2 

3 

4 

5 

6 

7 

8 

Autoclave 

on  site 

in  the  building 

in  suite 

in  lab  =  double 
ended 

SYSTEM  OF  WORK 

9 

Restricted  access 

10 

11 

12 

Biohazard  signs  on  the  door 

Control  of  aerosol  formation 

Washing  and  decontamination 
provisions  for  personnel 

no 

no 

no 

yes 

yes 

yes 

yes 
minimize 

yes 

yes 

yes 

yes 
prevent 

yes 

yes 

yes 

yes 
prevent 

yes 

Isolation  = the laboratory  is separated  from  other areas in the same building or is in a separated building. 
Airlock  = Entry  must  be  through  an  airlock  which  is a  chamber  isolated  from  the  laboratory.  The  clean  side  of  the  airlock 
must be separated  from  the restricted  side by changing or showering  facilities  and  preferably  by  interlocking doors. 
HEPA  = High  Efficiency  Particulate Air. 
Activities where transmission  does not occur  via airborne route. 

41 

Containment and Control  Measures  for Laboratory  Activities 

Specifications 

Containment  levels 

SYSTEM  OF  WORK 

13 

Shower 

1 

no 

2 

no 

14 

Protective  clothing 

labcoat 

labcoat 

3 

4 

optional 

yes 

suitable 
protective 
clothing  +  foot 
wear 

complete 
change  of 
clothing  +  foot 
wear  before 
entry  and  exit 

15 

16 

Gloves 

Test  adequately  and  maintain 
control  measures  and  equipment 

17 

Record  keeping 

no 

yes 

yes 

18 

Efficient  vector  control  (e.g.  for 
rodents  and  insects) 

optional 

optional 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

WASTE 

19 

Inactivation  of  GMMs  in 
effluent  from  handwashing  sinks 
or  drains  and  showers  if  any 

20 

Inactivation  of  GMMs  in 
contaminated  material  and  waste 

no 

no 

optional 

yes 

optional 

yes 

yes 

yes 

42 

Annex IV 
Table  I b 
Containment and Control  Measures  for Glasshouses  and Growthrooms 

The  terms glasshouse  and  growthroom  refer  to  a structure  with  walls, a roof  and  a floor  designed 
and  used  principally  for  growing  plants  in  a controlled  and  protected  environment. 

All  provisions  of  Table  I  a shall  apply  with  the  following  additions/modifications: 

Specifications 

Containment  levels 

BUILDING 

1 

Greenhouse  :  permanent 
structure(5) 

EQUIPMENT 

Surroundings  without 
susceptible  plant  species 

Entry  via  a  separated  room 
with  two  interlocking  doors 

1 

no 

2 

yes 

no 

optional 

optional 

optional 

3 

yes 

yes 

yes 

4 

yes 

yes 

yes 

Control  of  contaminated  run-off 
water 

optional 

minimize(6) run 
off 

prevent  run-  off 

prevent  run-off 

SYSTEM  OF  WORK 

Restricted  access 

Measures  to  control  undesired 
species  as  insects,  rodents, 
arthropods 

Procedures  for  transfer  of  living 
material  between  the 
glasshouse/growth  room, 
protective  structure  and 
laboratory  shall  prevent 
dissemination  of  genetically 
modified  microorganisms 

yes  (visitors 
accepted) 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

minimize 
dissemination 

minimize 
dissemination 

prevent 
dissemination 

prevent 
dissemination 

The  glasshouse  shall  consist  of  a  permanent  structure  with  a  continuous  waterproofed  covering,  located  on  a  site  graded  to 
prevent  entry  of  surface  runoff  having  self-closing  lockable  doors. 
Where  transmission  can  occur  through  the  ground. 

43 

2 

3 

4 

5 

6 

7 

Annex IV 
Table  I c 
Containment and Control  Measures  for Activities  in Animal  Units 

All  provisions of  Table I  a shall  apply  with  the following  additions/modifications: 

Specifications 

Containment  levels 

1 

2 

3 

4 

5 

FACILITIES 

Isolation  of  animal  unit(7) 

Animal  facilities(8)  separated  by 
lockable  doors 

Animal  facilities  design  for 
decontamination  (waterproof 
and  easily  washable  material 
(cages,  etc.)) 

Floor  and/or  walls  easily 
washable 

Animal  containment  in 
appropriate  cages,  pens  or 
tanks 

6 

Filters  on  isolators(9) 

1 

optional 

yes 

2 

yes 

yes 

optional 

optional 

3 

yes 

yes 

yes 

4 

yes 

yes 

yes 

yes  (floor) 

yes  (floor) 

yes  (floor  and 
walls) 

yes  (floor  and 
walls) 

yes 

no 

yes 

yes 

yes 

no 

optional 

yes 

(7) 

(8) 

(9) 

Animal  unit: a building,  or separate  area within  a building  containing  facilities  and other areas such as changing  rooms, showers,  autoclaves, 
food  storage  areas  etc. 
Animal  facility:  a  facility  normally  used  to  house  stock,  breeding  or  experimental  animals  or  one  which  is  used  for  the  performance  of 
minor  surgical  procedures. 
isolators:  transparent  boxes  where  the  animal  is  contained  within  or  outside  a  cage. 

Annex IV 
Table II 
Containment and Control  Measures  for other Activities 

Specifications 

GENERAL 

1 

Viable  micro-organisms  should  be  contained  in  a  system 
which  physically  separates  the  process  from  the  environment 
(closed  system) 

2 

Control  of  exhaust  gases  from  the  closed  system 

Control  of  aerosols  during  sampling  collection,  addition  of 
material  to  a  closed  system  or  transfer  of  material  to  another 
closed  system 

Inactivation  of  bulk  culture  fluids  before  removal  from  the 
closed  system 

1 

no 

no 

no 

no 

Containment  levels 

2 

-

3 

4 

yes 

yes 

yes 

yes, 
minimize 
release 

yes, 
minimize 
release 

yes,  by 
validated 
means 

minimize 
release 

yes, 
prevent 
release 

yes, 
prevent 
release 

yes,  by 
validated 
means 

prevent 
release 

yes, 
prevent 
release 

yes, 
prevent 
release 

yes,  by 
validated 
means 

prevent 
release 

yes 

yes 

Seals  should  be  designed  so  as  to  minimize  or  prevent 
release 

no 
specific 
requirement 

The  controlled  area  should  be  designed  to  contain  spillage  of 
the  entire  contents  of  the  closed  system 

optional 

optional 

yes 

The  controlled  area  should  be  sealable  to  permit  fumigation 

EQUIPMENT 

Entry  via  airlock 

no 

no 

no 

optional 

no 

optional 

yes 

Surfaces  resistant  to  acids,  alkalis,  solvents,  disinfectants 

optional 

optional 

yes 
(bench  if 
any,  floor) 

The  controlled  area  should  be  adequately  ventilated  to 
minimize  air  contamination. 

The  controlled  area  should  be  maintained  at  an  air  pressure 
negative  to  the  immediate  surroundings 

Extract  and  input  air  from  the  controlled  area  should  be 
HEPA  filtered 

optional 

optional 

optional 

no 

no 

no 

no 

optional 

yes 
(extract 
air, 
optional 
for  input 
air) 

yes 
(bench, 
floor, 
ceiling, 
walls) 

yes 

yes 

yes  (input 
and 
extract 
air) 

45 

3 

4 

5 

6 

7 

8 

9 

10 

11 

12 

Containment and Control  Measures  for other Activities 

Specifications 

Containment  levels 

SYSTEM  OF  W O RK 

13 

Closed  systems  should  be  located  within  a  controlled  area 

14 

15 

16 

Access  should  be  restricted  to  nominated  personnel  only 

Biohazard  signs  should  be  posted 

Washing  and  decontamination  provisions  for  personnel 

17 

Personnel  should  shower  before  leaving  the  controlled  area 

18 

Personnel  should  wear  protective  clothing 

1 

2 

no 

no 

no 

yes 

no 

optional 

yes 

yes 

yes 

no 

yes  (work 
clothing) 

yes  (work 
clothing) 

3 

yes 

yes 

yes 

yes 

optional 

yes 

19 

Test  adequately  and  maintain  control  measures  and 
equipment 

20 

Record  keeping 

21 

Appropriate  training  and  supervision  for  personnel 

WASTE 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

4 

yes 

yes 

yes 

yes 

yes 

complete 
change 
before 
exit  and 
entry 

yes 

yes 

yes 

22 

23 

24 

Inactivation  of  GMMs  in  effluent  from  handwashing  sinks 
and  showers  if  any 

no 

no 

optional 

yes 

Inactivation  of  GMMs  in  contaminated  material  and  waste 

optional 

yes 

yes 

yes 

Inactivation  of  GMMs  in  process  effluent  before  final 
discharge 

optional 

yes, by 
validated 
means 

yes,  by 
validated 
means 

yes,  by 
validated 
means 

4£ 

(Partially  Redrafted) 

ANNEX  V 

PART  A 

Information  required  for  the notification  referred  to in Article  7: 

those  responsible  for  supervision,  safety  and 

name  of  user(s)  including 
information  on  their  training  and  qualifications; 
details  of  any  biological  committees  or  subcommittees; 
address of  installation; 
general  description  of  the premises; 
a description  of  the nature  of  the work  which  will  be  undertaken; 
the class  of risk of  the  activities; 
a  summary  of  the  risk  assessment  referred  to  in  Article  5  (3)  (only  for  class  1 
activities) 

PART  B 

Information  required  for  the notification  referred  to in  Article  9: 

the date of  submission  of the notification  referred  to  in  Article  7; 
the recipient, donor  and/or parental  micro-organism(s) used  and,  where 
applicable, the host-vector  system(s)  used; 
the  source(s)  and  the  intended  function(s)  of  the genetic  material(s)  involved 
in the manipulation(s); 
identity  and  characteristics  of the genetically  modified  micro-organism(s); 
the purpose  of the contained  use including  the expected  results; 
approximate  culture  volumes  to be  used; 
description  of  the containment  and control  measures  to be applied,  including 
information  about  the wastes  to be generated, their treatment,  ultimate  form 
and  destination; 
a  summary  of the  risk  assessment  referred  to in  Article  5 (3). 

PART  C 

Information  required  for  the notification  referred  to  in Article  10: 

a) 

- 

the date of  submission  of  the notification  referred  to in  Article  7; 
name of  the responsible  person; 

b) 

- 

the recipient  or parental  micro-organism(s)  to be  used; 
the host-vector system(s) to  be used  (where  applicable); 
the  source(s)  and  intended  function(s)  of  the  genetic  material(s)  involved  in  the 
manipulation(s); 
identity  and  characteristics  of the genetically  modified  micro-organism; 

47 

the culture  volumes  to  be  used; 

c) 

- 

description  of  the  containment  and  control  measures  to  be  applied,  including 
information  about  the  type  and  form  of  wastes  to  be generated, their  treatment, 
ultimate form  and  destination; 
the  purpose  of the  contained  use including  the expected  results; 
description  of  the  sections  of the  installation 

d) 

information  about  accident  prevention  and emergency  response plans, if any: 

the  sources  of hazards  and  conditions  under which  accidents  might  occur; 
any  specific  hazards  arising  from  the location  of the  installation; 
the  preventive  measures  applied  such  as  safety  equipment,  alarm  systems  and 
containment  methods; 
procedures  and  plans  for  verifying 
containment  measures; 
a description  of  information  provided  to workers; 
the information  necessary for the Competent Authority to evaluate any emergency 
response  plans  prepared  in  accordance with  Article  14; 

the  continuing  effectiveness  of 

the 

e) 

a copy  of the risk assessment  referred  to in Article  5 (3). 

48 

ISSN 0254-1475 

COM(95) 640 final 

DOCUMENTS 

EN 

14  15  03 

Catalogue number  :  CB-CO-95-730-EN-C 

ISBN 92-77-98191-1 

Office for Official Publications of the European Communities 

L-2985 Luxembourg