REPORT FROM THE COMMISSION Experience of Member States with Directive 2009/41/EC of the European Parliament and of the Council of 6 May 2009 on the contained use of genetically modified micro-organisms for the period 2014 – 2018
Date: 2021-05-31
Institutions: Directorate-General for Health and Food Safety, European Commission
Subjects: EU Member State, application of EU law, chemical accident, environmental impact, environmental risk prevention, genetically modified organism, health control, microorganism, waste disposal

EN 

  EN 

   EUROPEAN COMMISSION  Brussels, 31.5.2021  COM(2021) 266 final  REPORT FROM THE COMMISSION Experience of Member States with Directive 2009/41/EC of the European Parliament and of the Council of 6 May 2009 on the contained use of genetically modified micro-organisms for the period 2014 – 2018 {SWD(2021) 114 final}  
 
 
REPORT FROM THE COMMISSION 

Experience of Member States with Directive 2009/41/EC of the European Parliament 
and of the Council of 6 May 2009 on the contained use of genetically modified micro-
organisms for the period 2014 – 2018 

The  information  contained  in  this  document  has  been  compiled  by  the  Commission  from 
individual  reports  submitted  by  Member  States  in  accordance  with  Article  17  of  Directive 
2009/41/EC  of  the  European  Parliament  and  of  the  Council1  on  the  contained  use  of 
genetically modified micro-organisms.  

INTRODUCTION 

Directive  2009/41/EC  (hereinafter  referred  to  as  "the  Directive")  provides  that  every  three 
years Member States send to the Commission a summary report on their experience with the 
Directive2  and  that  the  Commission  publish  a  summary  based  on  these  reports3.  The 
Commission has already published four reports pursuant to that directive or to the preceding 
Council Directive 90/219/EEC4, for the periods 1999-2003, 2003-2006, 2006-2009 and 2009-
20145. 

The  present  report  covers  the  period  from  June  2014  to  December  2018.  Two  rounds  of 
consultation of Member States were performed: 

1.  A first consultation (run in the first quarter of 2018) to cover the period June 2014 – 
December  2017:  all  Member  States  sent  individual  reports,  based  on  a  common 
questionnaire providing information on: 

  General implementation of the Directive; 
  Overview of the contained uses and premises for GMMs6; 

  Notification,  authorisation  and  administration  of    investigational  medicinal  products 

that contain or consist of GMOs; 

  Notifications and measures for gene drive modified organisms. 

2.  An additional consultation  (run in  the first  quarter of 2019) for the  period January  – 
December  2018  was  performed,  with  an  updated  version  of  the  questionnaire,  to 
receive  information regarding  notifications  of  contained  uses  of  GMMs/GMOs 
produced with new mutagenesis techniques and regarding the impact of the ruling of 

1 Directive 2009/41/EC of the European Parliament and of the Council of 6 May 2009  on the contained use of 
genetically modified micro-organisms (OJ L 125, 21.5.2009, p. 75) 
2 Article 17(2) 
3 Article 17(3) 
4 Council Directive 90/219/EEC of 23 April 1990 on the contained use of genetically modified micro-organisms 
(OJ L, 117, 8.5.1990, p. 1) 
5 The reports are available on this European Commission webpage. 
6 And for GM animals/GM plants if also covered under national contained use legislation 

1 

 
 
 
 
 
 
 
                                                 
the  Court  of  Justice  of  the  European  Union  (CJEU)  of  25  July  2018  in  Case 
C-528/167.  

For the year 2018, 25 Member States submitted their individual reports8. Croatia provided a 
statement on the “Directive 2009/41/EC and new mutagenesis techniques”. Therefore, Croatia 
contribution  for  the  year  2018  is  only  referred  to  in  the  part  related  to  new  mutagenesis 
techniques. In addition, Spain and the Netherlands referred in some part of their replies to the 
questionnaire, to comments provided as a follow-up of the Standing Committee on GM food 
and feed (September 2018), and the Regulatory Committee under Directive 2001/18 (October 
2018)  where  competent  authorities  were  requested  to  provide  information  relevant  to  the 
implementation of the Court ruling.  

The  following  text  summarises  the  information  given  by  the  Member  States  under  the 
headings provided and highlights similarities and differences between the experiences of the 
Member States.  Furthermore, it provides the Commission’s views on some  questions raised 
by Member States regarding the implementation of the Directive, notably as regards the scope 
of the Directive and the relevance of the Court ruling in Case C-528/16.    

Further details from the individual Member States' reports are provided in the accompanying 
Commission Staff Working Document.  

It should be noted that while the Directive provides for “common measures for the evaluation 
and  reduction  of  the  potential  risks  arising  in  the  course  of  all  operations  involving  the 
contained  use  of  GMMs  and  to  set  appropriate  conditions  of  use”  (Recital  8),  the 
implementation of the Directive is the responsibility of Member States. In particular, Member 
States when transposing the Directive into their national legislation could for example decide 
to  implement  more  stringent  requirements,  in  accordance  with  Article  193  TFEU.  Member 
States may also apply the principles of the Directive to GM animals and GM plants, as it is 
currently not regulated under Union legislation. 

The Commission organises regular meetings of the national competent authorities responsible 
for the Directive, where discussion on topics of common interest between Member States are 
discussed. 

Disclaimer: The information contained in this report relating to Member States is based on 
Member States’ individual reports. 

Neither  the  European  Commission  nor  any  person  acting  on  its  behalf  is  responsible  for 
the content of that information and of any use made of it. 

Clarifications provided in the report addressing questions by Member States reflect the views of 
the  European  Commission.  However  only  the  Court  of  Justice  of  the  European  Union  is 
competent to authoritatively interpret Union law. 

7  Judgment  of  25  July  2018,  Case  C-528/16,  Confédération  paysanne  and  Others  v.  Premier  ministre  and 
Ministre de l’agriculture, de l’agroalimentaire et de la forêt (ECLI:EU:C:2018:583) 
8 Croatia, Italy and Poland did not sent individual reports. 

2 

 
 
 
 
 
 
 
 
 
 
                                                 
PART I: GENERAL IMPLEMENTATION OF THE DIRECTIVE 

1. 

Notification and approval systems (and relevant changes)  

1.1 Approval systems 

As reported previously, national systems differ slightly in terms of authorities involved. Only 
Latvia  reported a  change9  in  the involved competent  authority,  as  compared to  the previous 
reporting period.  

In  many  Member  States  (Belgium,  Bulgaria,  the  Czech  Republic10,  Denmark11,  Ireland, 
Greece,  Spain12,  Latvia,  Lithuania,  Malta,  the  Netherlands,  Poland,  Portugal,  Romania, 
Slovenia,  Slovakia,  ),  the  competent  authorities  for  the  Directive  were  the  Ministry  of 
Environment  or  Agencies  focusing  on  environmental  issues.  In  case  of  GMO,  Food  and 
Veterinary authorities/directorates are also involved (Portugal, Slovenia13). 

In  other  Member  States,  the  tasks  of  the  competent  authority  were  carried  out  by  other 
Ministries,  such  as  the  Ministry  of  Health  (Croatia14,  Italy,  Luxembourg  and  the  United 
Kingdom), the Ministry of Labour (Estonia, Cyprus and Austria15), the Ministry of Education 
and  Research  (France16  and  Austria17),  the  Ministry  of  Agriculture  (Hungary18),  or  specific 
authorities  for  Biotechnology/Biosafety  (Finland19),  Food  Safety  and  Consumer  Protection 
(Germany) or Work Environment (Sweden20). 

In many Member States, the competent  authority is assisted by advisory scientific bodies in 
the risk assessment/authorisation process21. 

In some Member States, the implementation is done by competent authorities at regional level 
(Belgium,  Germany,  Spain22  and  the  United  Kingdom),  possibly  further  coordinated  at 
national  level  (Belgium,  Germany).  In  addition,  in  some  Member  States,  the  competent 

9 From Ministry of Agriculture to Ministry of Environment. 
10 In close collaboration with the Ministry of Health and the Ministry of Agriculture. 
11 Together with the working environment authority. 
12 In association with the Inter-ministerial Council for GMOs (CIOMG), which delivers the authorisation, for the 
contained  uses  carried  out  by  Government  Public  Research  Institutes  or  for  activities  with  GMOs  focused  on 
medical purposes (clinical trials, human and animal medicines/vaccines, etc). 
13  For  GM  animals,  registration  of  the  premises  involves  the  Veterinary  authority,  which  operates  under  the 
Ministry of agriculture, food and forestry. 
14 Together with the Ministry of Science and Education.  
15 For contained uses other than those in Universities and scientific institutions. 
16 Or Ministry of Defense for establishments under its authority. 
17 For contained uses in Universities and scientific institutions. 
18 Together with the National Institute of Pharmacy and Nutrition. 
19 Together with the National Supervisory Authority for Welfare and Health, as supervisory authority. 
20 For contained use of GMMs. The Swedish Agency for Marine and Water Management is involved in case of 
contained use of water living GMO; for other contained uses, it is the Swedish Board of Agriculture.  
21 For example, Czech Commission for the Use of GMOs and Genetic Products; High Council for Biotechnology 
in France; Biotechnology Health Technical Committee in Italy; Commission on Genetic Modification (COGEM) 
in  the  Netherlands;  Directorate  General  of  Health  and  National  Health  Institute  Doutor  Ricardo  Jorge  in 
Portugal;  Biosafety  Commission,  and  various  authorities  according  to  the  type  of  use  in  Romania;  National 
Commission on Biosafety (CNB) in Spain, the Central Committee on Biosafety (ZKBS) in Germany.  
22 For other activities than those carried out by Government Public Research Institutes or activities with GMOs 
focused on medical purposes. 

3 

 
 
 
 
 
 
 
 
 
                                                 
authority varies according to the type of use (Spain, Sweden) or the type of premises (France, 
Austria).  

In  many  Member  States,  the  competent  authority  for  Directive  2009/41/EC  is  also  the 
competent  authority  for  Directive  2001/18/EC  on  deliberate  release  into  the  environment  of 
GMO, while for 10 Member States23 it is a distinct competent authority. 

The vast majority of Member States have extended the scope of their transposing legislation 
to  the  contained  use  of  GM  plants  and  GM  animals.  This  is  usually  because  the  national 
legislation covers all types of GM organisms:  GMMs, GM plants and GM animals24. Some 
Member  States25  extended  the  scope  of  their  transposing  legislation  specifically  to  require 
notification,  risk  assessment,  enforcement  and  appropriate  containment  measures  for 
contained  use  activities  with  GM  plants  and  GM  animals.  Finally,  Member  States  also 
referred to historical and political reasons (Denmark) and societal reasons (France), for such 
extension of the scope.  

To  note,  Bulgaria  uses  a  different  classification  for  GM  plants  and  animals,  with  only  two 
classes26, and Lithuania indicated that it will prepare specific requirements for the contained 
use of GM plants and GM animals.  

For  the  seven  Member  States27  that  have  not  extended  the  scope  of  their  transposing 
legislation, the reasons were diverse. While in general the transposition followed the scope of 
the Directive and its definition of GMM, in Cyprus, an extension of the scope was not needed 
because there are no activities and/or installations involving GMOs.   

Four Member States (the Czech Republic, the Netherlands, Portugal and Slovenia) reported a 
change in the notification and approval system compared to the last reporting period (2009-
2014).  

The Czech legislation is stricter than the Directive for Class 1 contained uses28. According to 
the amendment (which came into force on 1st January 2017), when carried out in a previously 
notified  Class  1  premises,  the  user  has  to  submit  a  notification  but  can  already  start  the 
activity.  The  competent  authority  assesses  the  notification  and  may  require  additional 
information from the notifier and/or decide that the contained use has to be suspended.  

The  Czech  Republic  and  the  Netherlands  also  declared  that  new  notifications  formats 
(harmonised  tables  for  the  risk  assessment,  presentation  of  the  data)  and  reporting  systems 
have been put in place. This enhanced clarity for the notifiers and the competent authorities, 
which further ease the reviewing by the competent authority.  

The new Portuguese law clarified the legal framework for the contained use of GM plants and 
GM animals, set a deadline to the consulted entities for issuing opinions and introduced the 
obligation for notifiers to report annually on contained uses of GMMs and GMOs. 

23 BE, CY, DE, EE, EL, FR, HR, IT, SE and UK. 
24 BE, BG, DE, DK, ES, FR, NL, AT, PT, SI, FI and UK. 
25 BE, BG, CZ, IE, HR, HU, PL, SK and UK. 
26 Class A: no or negligible risk for the human or animal health and for the environment; class B: all other cases. 
27 EE, EL, IT, LV, LU, CY and RO.  
28 Until the end of 2016, a new notification was already required for each new activity carried out in a previously 
notified Class 1 premises. 

4 

 
 
 
 
 
 
 
 
 
 
                                                 
Slovenia reported a change in the administrative procedures (some costs to be covered by the 
notifier in specific cases). 

1.2 Notification process 

During  this  period,  most  Member  States  processed  the  notifications29  within  the  statutory 
timeframe30,  while  11  Member  States31  declared  delays  (usually  for  less  than  15%  of  the 
assessed  notifications32).  Greece  and  Latvia  reported  that  there  were  no  notifications 
submitted during this period, and Luxembourg, which has an authorisation procedure in place, 
does not apply any notification process. 

When  delays  occurred,  they  were  mostly  due  to  some  peaks  in  the  number  of  notifications 
submitted (Germany and France), insufficient staff resources compared to the workload in the 
competent authority (Germany) or the consulted scientific bodies, or change of the Committee 
members  (Croatia,  Italy,  Slovenia  and  Sweden).  Furthermore,  Italy  reported  to  have  no 
effective IT tools to archive and retrieve all the information provided by the users.  
Waiting for additional information from the notifier after a request by the competent authority 
is also causing delays (Belgium, France, Italy and Sweden). However, in Belgium and Spain, 
which  both  include  an  on-site  visit  in  their  assessment,  the  timeframe  for  the  notification 
assessment  can  be  suspended  if  the  competent  authority  is  waiting  for  complementary 
information from the users. 

Administrative  issues  linked  to  consulted  scientific  bodies  or  other  authorities  (Germany, 
Italy,  Slovenia,  Slovakia  and  the  United  Kingdom)  were  also  causing  delays.  Slovakia 
considers that the time during which the competent authority is waiting for the opinion of its 
advisory body should not be taken into account.  

In  Belgium, different  procedures  apply  according to  the regions,  and in  the Flemish Region 
there  are  two  authorisations  processes  with  different  timeframes  which  are  linked 
(authorisation  for  the  contained  use,  45  or  90  days;  environmental  permit,  up  to  6  months), 
possibly  impacting  the  contained  use  authorisation  as  it  can  be  given  only  after  the 
environmental permit is granted. The Netherlands had also delays due to the implementation 
of the new rules of the revised GMO Decree.  

Finally, Germany, the Netherlands and Slovakia highlighted that the increasing complexity of 
the notifications makes the processing time longer.  

Member States were taking measures to reduce or prevent delays in processing notifications 
(unless those delays were unusual and unlikely to be repeated, like in the United Kingdom). 
For  example,  France  adjusted  the  resources  to  the  amount  of  notifications  received  and 
Luxembourg to perform field inspections.  

29 “Notification”: the presentation of the requisite information to the competent authorities of a Member State. 
30 Articles 8(2), (3) and 9(2) of the Directive. 
31 BE, DE, IE, FR, HR, HU, IT, NL, SI, SE and UK.  
32 With the exception of two Member States, which reported 50% of notifications processed with delay (Slovenia 
in the period of 2014-2017, France for the year 2018). 

5 

 
 
 
 
 
 
 
 
 
 
  
 
                                                 
Member States are also improving the communication between the different parties involved: 
between the notifiers and the competent authority (including consultation prior to submission 
in Hungary, tracking of notifications with a unique notification number in Sweden); between 
the  competent  authority  and  the  consulted  scientific  body.  For  example,  in  Italy  efforts  are 
being  made  to  provide  a  web  platform  to  the  competent  authority  and  the  scientific  board 
members  to  share  the  notifications  electronically  and  to  obtain  signed  opinions  by  each 
member of the scientific board. Finally, users and authorities also  adjusted to  new practices 
when introduced (the Netherlands). 

Regarding  the  notification  process  in  general,  half  of  the  Member  States33  that  received 
notifications do not encounter specific difficulties. 

In addition to previous comments, some Member States further reported difficulties related to 
the  quality  and  completeness  of  the  submitted  notifications  (the  Czech  Republic,  Denmark 
Germany, Finland and Sweden). Moreover, notifiers can face issues to interpret some terms of 
the national legislation (case of the Flemish region of Belgium, where the user can submit a 
‘notification’ or an ‘admission request’ for subsequent class 2 contained uses). On the other 
hand, in the United Kingdom, the users understand well the notifications requirements and the 
notification process is working well. 

Denmark  and  Finland  noticed  administrative  burden  related  to  the  mobility  of  researchers 
between institutions, leading for example to repeated new notifications by the same notifier of 
different  premises,  or  to  the  lack  of  correct  notifications  for  new  uses.  It  also  happens  that 
when the premises is no longer used, the notifier forgets to inform the competent authority, or 
that after renovation of an old premises, the renovated structure does not correspond anymore 
to what had been notified. 

France and  Italy also reported difficulties related to  IT tools. Italy mentioned the lack of an 
electronic  system  that  would  allow  the  notifier  to  submit  and  update  its  notification 
electronically,  while  France  underlined  that  the  IT  tool  used  needs  further  development  to 
fulfil all the needs.  

More  generally,  Member  States  reported  issues  for  notifications  linked  to  the  definitions  of 
the Directive and the classification of the contained uses (see paragraph 6 Interpretation and 
implementation of the Directive, p. 12).  

To  help  improving  the  content  of  the  notifications,  some  Member  States34  suggested 
providing guidance and clarification on the notification requirements to the users, for example 
on the competent authority webpage or in guideline documents, or by providing consulting to 
the users. Better information and explanation provided to the consulted bodies involved in the 
assessment of the notifications was also mentioned.   

New  IT  tools  or  templates  were/could  also  be  developed35,  together  with  improving  the 
administrative procedures for more efficiency, and streamlining the practices.36 Sweden and 

33 CZ, EE, HR, CY, LT, HU, MT, AT, PL, PT, RO, SI, UK. 
34 BE, DK, DE, EE, IE, SI, FI. 
35 CZ, ES, FR, IT, NL. 
36 FR, NL. 

6 

 
 
 
 
 
 
 
 
 
                                                 
the Czech Republic reported that the changes done in their legislation contributed to ease and 
speed up the notification process. 

Aspects  specifically  related  to  clinical  trials,  and  interpretation  of  the  definitions  of  the 
Directive in relation with new genomic techniques are discussed in parts III (p. 20) and IV (p. 
24) respectively. 

2.  Waste disposal 

In general, Member States37 declare that waste is managed by class of contained use and type 
of waste, in accordance with the requirements of Article 5 and of Annex IV and Annex V of 
the Directive. Some Member States38 prescribe that all types of waste (including from class 1) 
must be inactivated prior to disposal. For waste resulting from class 1 use, Denmark and the 
United  Kingdom  mention  a  risk  assessment  in  each  specific  case,  and  Spain  recommends 
inactivation. The Member States39 that did not provide information on these aspects explained 
that there is no activity or no experience in this area.  

In general, the users apply autoclaving and chemical inactivation to inactivate GM waste on 
site, and incinerate GM plants and animals. Other treatments to inactivate waste for different 
tissues  of  a  GM-plant  or  animal  can  be  used  individually  or  combined  (alkaline  hydrolysis, 
UV treatments, freezing, mechanical treatments, composting). Other procedures are evaluated 
on a case-by-case basis  and are subject to  validation. For example, Germany  authorised the 
inactivation of soil containing GMO-seeds by a validated steam method.  

16 Member States40 indicated that they have waste treatment facilities authorised to inactivate 
waste arising from contained use premises. 

Many Member States41 reported that if inactivation of waste from class 1 and 2 is not possible 
in situ, or in case of large volume of waste, it is transported in properly sealed and labelled 
containers  to  a  dedicated  authorised  waste  facility,  by  specialised  transport  companies 
(certified  for  collection  of  hazardous  waste),  and  according  to  the  rules  for  the  transport  of 
dangerous goods42. Transport and disposal are recorded (Germany, the United Kingdom). In 
addition,  in  some  Member  States  (Spain,  France,  Malta,  Romania  and  Slovakia)  certified 
companies collect also inactivated waste. 

Nine  Member  States43  indicated  that  some  waste  from  contained  use  activities  is  recycled 
after  inactivation.  The  purposes  of  the  recycled  waste  are  compost,  fertilizer  and  biogas. 
Finland  noted  that,  as  the  concept  of  circular  economy  is  gaining  ground  in  the  EU,  the 
legislative  issues  on  recycling  large  quantities  of  GMM  waste  or  byproducts  should  be 
addressed.  

37 BG, CZ, DK, DE, ES, FR, HR, IT, CY, LU, AT, RO, SI, SK, FI and UK. 
38 BE, IE, LT, MT, NL, PT, SE. 
39 EL, LV. 
40 BE, DE, EE, IE, ES, FR, HR, LT, LU, HU, NL, RO, SK, FI, SE, UK.  
41 BE, DE, EE, IE, FR, HR, LU, NL, SK, FI, SE, UK. 
42  ADR,  formally  the European  Agreement  of  30  September  1957  concerning  the  International  Carriage  of 
Dangerous Goods by Road. 
43 BE, CZ (only in the period 2014-2017), DK, DE, LT (only in 2018), HU (only in 2018), SI, SK and FI.  

7 

 
 
 
 
 
 
 
 
 
 
 
                                                 
3.  Inspection and enforcement issues   

The  control  procedures  put  in  place  by  the  Member  States  included  regular  inspections 
according to set criteria (class of risk, periodicity, etc.), ad hoc unannounced inspections, and 
audits of premises approved for the first time. The inspections evaluated the compliance with 
the  Directive,  the  correctness  of  the  risk  assessment  classification,  the  effectiveness  of  the 
respective  containment  level,  the  labelling  and  transport  of  GMOs  within  the  premises,  the 
waste treatment, the training of the personnel, and the fulfilment of administrative obligations. 
In  some  cases,  it  included  also  sampling  of  materials.  Ireland  reported  using  a  checklist 
originally  adopted  by  the  European  Enforcement  Project  (EEP)  on  Genetically  Modified 
Organisms44 during its inspections. 

In  some  Member  States,  inspections  were  conducted  by  specialised  inspectors  from  the 
competent  authority,  while  in  others,  inspections  were  carried  out  at  the  request  of  the 
competent  authorities  by  specialised  inspectors  from  other  ministries  or  services.  In  some 
Member  States,  controls  are  carried  out  by  regional  authorities.  Some  Member  States 
developed  documentation  or  training  for  inspectors:  Italy  developed  a  training  course  for 
inspectors, Portugal established a guide to support the inspections, and Luxembourg designed 
a new inspection checklist and procedure.  

The  number  of  inspections  carried  out  during  the  reporting  period  varies  among  Member 
States,  from  10  to  100%  of  the  premises  controlled.  Few  countries45  did  not  carry  out  any 
inspection  during  the  reporting  period,  mostly  because  no  contained  use  premises/activities 
were notified. 

In many countries46, the inspections gave priority to premises of higher class of contained use, 
and to  new premises/activities. The frequency of  inspection varies according to the  class of 
use:  for  countries  with  premises  for  class  4  uses,  those  are  usually  inspected  annually.  The 
frequency  for  class  3  premises  varies  between  once  per  year  to  once  every  3  or  5  years.  In 
general,  class  1  and  class  2  premises  are  inspected  at  a  lower  frequency  than  class  3-4 
premises, and in  some countries those are controlled remotely, or they are not  controlled as 
part  of  a  proactive  inspection  programme.  Inspections  can  also  be  triggered  in  case  of 
incidents  or  accidents,  to  verify  the  implementation  of  corrective  measures.  Finally, 
unscheduled  inspections  may  take  place  when  unauthorised  use  of  GMO  is  suspected 
(Bulgaria). 

During inspections, some contained uses of GMOs/GMMs with no correct authorisation (not 
notified), or with incorrect classification of the contained use, were found, possibly leading to 
insufficient  containment  measures.  A  minority  of  Member  States  did  not  encounter  issues 
during inspections47.  

44 The European Enforcement Project on GMOs (EEP) is a network of regulators from inspectorates across the 
European  Union  (and  beyond)  responsible  for  the  inspection  of  activities  involving  GMOs.  The  network  was 
founded in 1997. 
45 IT, EL, LV, MT, PT. 
46 BE (Brussels-Capital Region), DE, IE, NL, FI, SE, UK. 
47 BG, HR, CY, LT.  

8 

 
 
 
 
 
 
 
                                                 
 
Among  the  issues  reported,  it  happened  that  procedures  described  in  the  notifications,  or 
laboratory  installations,  did  not  correspond  to  the  laboratory  practice/reality.  Other  reported 
issues concerned deficiencies in good laboratory practices (GLP) affecting the premises (e.g 
organisation,  inadequate  or  deficiencies  in  laboratory  equipment,  incorrect  labelling  of  the 
laboratory and equipment), the users (e.g inadequate protective clothing, missing instructions, 
insufficient  training)  or  the  administrative  procedures  (e.g  lack  of  complete,  up-to  date, 
accurate  documentation,  incomplete  recording  of  staff  working  in  the  premises).  Further 
issues related to the lack of appropriate procedures for inactivation of the GMMs and waste 
management,  as  well  as  insufficient  biosafety  measures  (e.g  no  restricted  access  to  the 
premises where the contained use takes place, insufficient hygiene and disinfection methods). 
Various  countries  reported  a  lack  of  internal  control  procedures  (e.g.  biosafety  officer  in 
charge of implementing properly the confined and control measures according to the class of 
risk).  Finally,  administrative  issues  (delayed  notification  of  changes  in  responsible  persons, 
missing recording of staff training, missing notification that a premises is no longer used for 
contained uses) were also found. 

In  terms  of  enforcement,  when  inspections  identified  situations  requiring  corrective  actions, 
the  competent  authorities  declare  to  have  used  a  number  of  instruments  (inspection  reports, 
letters, warnings, fines, etc.) to ensure remedial action and compliance from the users within a 
set timeframe.  

If the non-compliance issues could result in increased risk for human or animal health or for 
the environment, all activities involving GMOs would be immediately stopped and the GMOs 
destroyed. For minor issues (e.g. regarding documentation), the deficiencies were corrected at 
the time of the inspection. In general, users implemented the corrective actions requested by 
the authorities in the given timeframe, and competent authorities controlled this with follow-
up inspections, or by checking the updated documentation (including pictures). 

In  case  of  contained  use  or  premises  not  notified,  the  user  had  to  submit  the  appropriate 
notification, and in Slovakia, the competent authority imposes a fine to the user and publishes 
the corresponding decision online. 

If  issues  were  detected  before  the  start  of  the  contained  use,  users  had  to  correct  the 
deficiencies  before  beginning  the  activities.  In  some  cases,  the  competent  authority  would 
also add conditions in its approval decision for the notified contained use. On the other hand, 
Finland reported a case  were more information was  asked regarding a contained use, which 
was not notified appropriately and already finished, to assess the risks a posteriori. 

In order to minimise the occurrence of those issues, users provided more adequate protective 
equipment to the laboratory staff, as well as more information and training, including to the 
biosafety officers and with the staff in charge of waste management and maintenance of the 
infrastructures. In some cases, the users nominated a dedicated person for dealing with legal 
and  safety  requirements,  internal  controls,  and  liaising  with  the  competent  authorities.  The 
communication  between  users  and  competent  authorities  can  also  be  reinforced:  in  some 
Member States, the user asks questions to its competent authority prior to the notification, to 
get clarifications on the requirements and information about actions to be carried out.  

Some competent authorities also make recommendations, and disseminate various checklists, 
guidelines,  best  practices  and  methodology  documents  to  the  users.  Some  also  organised 
regular informative sessions, consultations with users, to raise awareness on biosafety before 

9 

 
 
 
 
 
 
 
 
approval  of  the  contained  uses.  They  also  organised  specific  trainings  about  the  legal 
requirements  for  GMMs/GMOs  uses  for  the  biosafety  officers,  and  emphasised  the 
importance of internal control procedures. The inspection visits are also used to discuss about 
plans for future contained uses where the users can get advices.  

Regarding the case of premises not used anymore, for which it happens that the user forgets to 
inform  its competent  authority, in  Slovenia, the competent  authority specifically  explains to 
the  user,  at  the  time  the  premises  is  notified,  the  conditions  for  a  future  deletion  of  the 
installation from the register of contained use premises.  

4.  

Accidents  

Very  few  Member  States  (Belgium,  Germany,  Finland  and  the  United  Kingdom)  reported 
accidents48, or some incidents (the Netherlands).  

Belgium  reported  one  accident  in  Wallonia  due  to  a  technical  failure.  An  external  expert 
analysed the corrective measures taken and the internal contingency plan, and gave advice on 
additional measures that should be taken.  

Germany  reported  four  accidents,  two  due  to  a  technical  failure  (water  leak  in  a  class  3 
premises, malfunction of a fermenter with a discharge of a large amount of GMM class 1 cell 
culture), one because of incorrect installation, and one related to the infection of a laboratory 
staff member. The competent authority was informed and corrective actions were taken by the 
users.  In  some  cases,  the  user  and  the  authorities  informed  also  the  public.  The  competent 
authority granted a permission to resume work only after completion of further actions by the 
user and performed follow-up inspections.  

Finland reported few needle stick accidents concerning employees working with GMMs, and 
also  a  case  of  an  effluent  overflow  in  a  class  1  premises.  In  the  latter  case,  technical 
improvements of the installation were done, as well as training of the staff to recognise and 
prevent  similar  situations  in  the  future.  The  competent  authority  examines  each  case  and 
decides whether these measures are sufficient, and the inspection services supervise that the 
corrective measures are actually implemented.  

The United Kingdom reported one accident, involving a person infected via needle stick while 
working  in  a  class  2  laboratory,  preparing  GM  non-replicative  oncogenic  Lister  vaccinia 
virus. The competent  authority carried out  a full investigation of the causes of the accident, 
which included an inadequate risk assessment for procedures and inadequate training for the 
use of sharps with GM biological agents, inadequate accident and emergency procedures, and 
failure to notify relevant people in a timely manner, and informed the Commission. Various 
measures  were  put  in  place  to  prevent  such  type  of  accident,  including  training  for  all  staff 
involved  in  GM  work,  review  of  the  risk  assessments  for  GMOs,  establishment  of  formal 
emergency  procedures,  and  formalisation  of  the  role  of  occupational  health  in  accident  and 
emergencies. 

48 According to the Directive, “accident” means any incident involving a significant and unintended release of 
GMMs in the course of their contained use which could present an immediate or delayed hazard to human health 
or the environment. 

10 

 
 
 
 
 
 
 
 
 
 
                                                 
The Netherlands reported several incidents due to needle stick injury. Usually the laboratory 
staff members were prescribed a curative medication, as a precautionary measure. There were 
also some incidents related to incorrect waste management, to technical failures or to the use 
of ineffective disinfectant, leading to the possible accidental release of small amount of GMO 
material (class 1 or class 2). Some of the incidents occurred during construction or renovation 
activities.  There  was  also  a  case  of  maintenance  work,  which  caused  a  change  from  under-
pressure  to  over-pressure  in  a  class  3  unit  not  yet  in  use  for  experiments.  In  those  reported 
cases, there was a follow-up between the biosafety officer and the competent authority. One 
case  led  to  a  follow-up  extensive  inspection.  It  was  required  that  technical  measures,  better 
procedures  and  safer  type  of  needles  were  put  in  place/used  to  prevent  similar  incidents. 
Maintenance  work  was  also  followed  by  internal  inspection  by  the  biosafety  officer  before 
contained use activities were re-started. 

The Commission notices a different perception of “accident” versus “incident” (which is not 
defined per se in the Directive) between Member States, and the classification of an event as 
“accident” is the responsibility of the competent authority, based on the risk for human health 
or  the  environment.  In  case  of  accident,  the  competent  authority  has  to  inform  the 
Commission,  according  to  article  15.1(b)  of  the  Directive,  and  according  to  article  15.2  the 
Commission shares this information with other Member States.  

5.  

Public consultation   

While some Member States49 do not carry out public consultations under their contained use 
legislation, the majority of them50 organised public consultations when appropriate, according 
to Article 12 of the Directive. 

The procedures for public consultation aim at providing general information to the public, or 
more  specifically  to  the  neighbourhood  of  the  premises,  regarding  the  contained  use  of 
GMMs and GMOs. The comments received from the public (usually in writing, but possibly 
through the organisation of public debates) are taken into account by the competent authority 
when  taking  its  decision  on  a  submitted  notification.  In  some  Member  States,  citizens  have 
the possibility to file a complaint after the approval of the contained use. 

Some Member States51 focus the public consultations only on class 3 and/or 4 contained use 
notifications.  In  other  Member  States,  the  public  consultation  is  carried  out  as  part  of  the 
authorisation of the premises52, under environmental permit procedures. 

Usually,  the  information  is  made  publicly  available  online.  It  contains  a  summary  of  the 
notification,  and  in  some  cases  the  risk  assessment  performed  by  the  user,  together  with 
emergency  plans.  The  information  can  also  be  published  in  national  and/or  regional 
newspapers. In some Member States, the information targets the neighbours of the contained 
use premises, with information displayed in the town hall, and at the premises. 

In Ireland and Italy, it is the duty of the user to inform the public of the submitted notification, 
via publishing it in a (local) newspaper. 

49 CZ, EE, CY, LV, MT, AT, PT, FI, SE. 
50 BE, DK, DE, IE, ES, FR, HR, LT, LU, HU, NL, PL, RO, SI, SK, UK. 
51 DE, IE, ES, IT, SI. 
52 BE, NL. 

11 

 
 
 
 
 
 
 
 
 
                                                 
In  general,  Members  States  reported  that  they  did  not  receive  responses  to  public 
consultations. In the Netherlands the received comments focused on the overall premises, and 
very rarely on the GMO aspects.  In the United Kingdom, the responses to the consultations 
were predominantly supportive of the proposals  (a summary is  also  published online). Only 
Belgium reported an observation received for a notification of a class 2 GMO contained use, 
concerning the proximity of the laboratory to houses and a school.  

Finally, in several Member States, information on the premises for contained use of GMMs 
and GMOs is maintained updated and available online53. 

6. 

Interpretation and implementation of the Directive  

While many Member States54 reported no specific difficulties regarding the interpretation of 
the  Directive,  those  that  reported  issues  often  refer  to  problems  with  the  definition  of 
GMMs/GMOs in the context of new genomic techniques, and synthetic biology, and whether 
a specific technique and the resulting organism fall within the scope of the Directive55.  

In  general,  this  leads  to  situations  where  both  the  operators  and  competent  authorities  are 
uncertain  whether  a  notification  is  actually  required  or  not.  In  some  cases,  the  competent 
authority had to decide on the application or not of the Directive. 

6.1 New mutagenesis techniques  

As explained in the introduction, the consultation of Member States was done in two phases: a 
first phase for the period 2014-2017, with replies submitted before the ruling of the CJEU of 
25  July  2018  in  case  C-528/16  on  new  mutagenesis  techniques.  On  that  occasion,  some 
Member  States  (Belgium,  the  Czech  Republic,  Germany,  Ireland,  Spain  and  the  United 
Kingdom)  considered  that  a  harmonised  legal  interpretation  at  EU  level  on  the  regulatory 
status of GMOs obtained with new genomic techniques was urgently needed.  

A second consultation phase of Member States covered the year 2018 (with replies provided 
interpretation  and 
in  2019).  During 
implementation of the Directive focused on notifications of contained uses of GMMs/GMOs 
produced with new mutagenesis techniques, and on the impact of the ruling for the competent 
authorities. 

that  second  consultation,  questions  related 

to 

judgment, 

the  2018 

the  Court  ruled 

In 
that  organisms  obtained  by  means  of 
techniques/methods  of  mutagenesis  constitute  genetically  modified  organisms  within  the 
meaning of Article 2(2) of Directive 2001/18/EC, and that only organisms obtained by means 
of techniques/methods of mutagenesis which have conventionally been used in a number of 
applications  and  have  a  long  safety  record  are  excluded  from  the  scope  of  that  directive  in 
accordance with Article 3(1) thereof.  

In  the  Commission’s  view,  the  Court’s  interpretation  of  the  exemption  in  Article  3(1)  of 
Directive  2001/18,  read  in  combination  with  Annex  IB  to  that  Directive  as  regards 
mutagenesis techniques, also applies to the exemption of mutagenesis techniques in Directive 

53 BG, LT, NL, PL, RO, SK, UK. 
54 EE, EL, FR, HR, CY, LV, LT, LU, MT, AT, PL, PT, RO, SI, SK, UK. 
55 BE, CZ, DE, IE, ES, HU, NL, FI, SE. 

12 

 
 
 
 
 
 
 
 
 
 
 
                                                 
2009/41/EC.  This  conclusion  is  supported  by  various  considerations,  namely  by  the 
similarities  between  the  two  directives  as  regards  their  aim,  the  definitions  of  GMO/GMM 
and  the  construction  of  the  exemption  (i.e.  by  the  combination  of  an  Article  formulated  in 
similar terms in both directives and an Annex listing the exempted techniques); the fact that 
the predecessors of both directives (Directives 90/220/EEC and 90/219/EEC) also followed a 
similar  approach  as  regards  the  scope  of  the  exemptions;  and,  finally,  the  fact  that  the 
techniques exempted in Annex II, part A of Directive 2009/41 had a safety record at the time 
of  the  adoption  of  Directive  90/219/EC,  which  tends  to  confirm  that  the  rationale  for  the 
exemption is the same in Directive 2009/41 as in Directive 2001/18. 

From  the  above  it  can  be  concluded  that  microorganisms  obtained  by  means  of 
techniques/methods of mutagenesis which have not been conventionally used in a number of 
applications  and  do  not  have  a  long  safety  record  are  not  exempted  from  Directive 
2009/41/EC.  

  Notifications  of  contained  uses  of  GMMs/GMOs  produced  with  new  mutagenesis 

techniques 

Various Member States indicated that they did not receive any notifications for GMMs/GMOs 
obtained  with  new  mutagenesis  techniques  (Bulgaria,  Denmark,  Estonia,  Greece,  Cyprus, 
Latvia,  Lithuania,  Luxembourg,  Malta,  Hungary  and  Portugal).  Germany  indicated  that  a 
significant proportion of activities involving new mutagenesis techniques is not notified to the 
competent  authority  since  no-risk  or  low-risk  activities  only  need  to  be  recorded  by  the 
researcher, not notified. Finland stated that specific details of the techniques used to produce 
the GMMs/GMOs are not notified to the competent authority. Other Member States (Ireland, 
Austria,  Romania,  and  Slovakia)  reported  between  1  and  10  notifications  for  such 
GMMs/GMOs,  including  a  commercial  do-it-yourself  kit.  Belgium,  the  Czech  Republic, 
Spain,  France,  Croatia56,  Slovenia,  and  the  United  Kingdom  also  received  notifications, 
mostly  for  GMMs,  and  also  for  GM  plants  and  GM  animals  (mice,  xenopus).  The  United 
Kingdom  estimates  that  among  the  220  notifications  received  in  2018,  half  involve  new 
mutagenesis  techniques,  while  France  reports  a  stable  number  of  notifications  over  the  past 
four years, with around 1000 requests per year.  

Sweden  considers  unfortunate  that  the  CRISPR-Cas-techniques  are  interpreted  as  only  one 
type. They have several GMM uses involving CRISPR-Cas and gene editing, where both the 
Cas-gene  and  gRNA  are  provided  by  vectors  in  cells  (or  cells  in  laboratory  animals).  The 
purpose  of  those  experiments  is  often  to  explore  gene  function,  and  the  cell  cultures  or 
laboratory  animals  are  only  used  for  the  purpose  of  such  experiments.  Hence,  according  to 
Sweden,  there  is  no  commercial  aspect  for  not  calling  the  experiments  “contained  use  of 
GMM”. 

Bulgaria, the Czech Republic, Ireland, Spain, Croatia,  and the Netherlands reported that they 
considered  products  obtained  by  new  mutagenesis  techniques  as  GMOs,  in  scope  of  EU 
legislation  and  of  their  national  legislation,  and  assessed  them  as  such  (already  before  the 
Court ruling). 

56 Croatia did not submit its questionnaire for the year 2018, but provided a statement on the Directive and new 
mutagenesis techniques.  

13 

 
 
 
 
 
 
 
                                                 
Sweden specified that it interprets "mutagenesis" as the well-known techniques with chemical 
or physical mutation methods, common at the time of the first Directive on contained use of 
GMM from 1990 (90/219/EEC57) and not the later methods involving nucleic acids and site 
specificity, but for Sweden, it is difficult to understand why some "new" methods should be 
included and why some should not. 

In Germany, several but not all of the regional competent authorities have regulated genome-
edited organisms as genetically modified organisms on a precautionary basis before the Court 
ruling.  After  the    Court  ruling,  the  regional  competent  authority  concluded  that  - 
precautionary  and  unless  otherwise  stated  -  all  organisms  obtained  using  mutagenesis 
methods are to be regarded as GMOs, also within the meaning of the Directive on contained 
use.  However,  the  Court  ruling  has  brought  more  clarity  to  the  debate,  but  it  also  poses 
challenges that still need to be resolved. 

Some  Member  States  indicated  that  they  asked  or  will  provide  clarifications  to  users:  the 
Hungarian competent authority requested users to report about all class 1 activities, including 
activities  on  new  mutagenesis  techniques,  and  informed  them  about  the  ruling  and  the 
necessity  to  submit  notifications  for  class  2,  3  and  4  contained  uses,  if  applicable.  In  the 
United  Kingdom,  the  contained  use  guidance,  which  was  last  updated  in  2014,  will  be 
updated to remove ambiguity relating to what may be considered as mutagenesis to bring it 
into line with the Court ruling.  

 

Impact of the Court ruling on new mutagenesis for the competent authorities 

Some countries have no specific views on it (Denmark, Estonia, Cyprus, Malta, Romania and 
Sweden) and Portugal and Slovakia still need to evaluate it.  

A number of countries indicate that it has no impact as  risk assessment and management of 
contained uses of GMMs and GMOs obtained by new techniques are performed in the same 
way  as  other  GMOs  (Belgium,  Germany,  and  the  Netherlands).  It  is  the  same  in  Austria, 
which  specified  that  all  new  mutagenesis  techniques  are  fully  covered  by  its  national 
legislation (only non-directed mutagenesis is  exempted). For the United  Kingdom,  little has 
changed  regarding  the  Directive,  since  conventional  mutagenesis  continues  to  be  exempted. 
There is also no impact for Greece, which did not receive any notification for contained use of 
GMMs.  Latvia  and  Slovenia  have  so  far  no  specific  issues  (new  techniques  not  yet  widely 
used in Latvia, while they are used in research laboratories in Slovenia and all activities are 
notified).  

On  the  other  hand,  Bulgaria,  Germany  and  Ireland  mentioned  difficulties  in  applying  and 
enforcing the contained use legislation for GMOs obtained through new genomic techniques 
due to their detection and identification, and the difficulty to distinguish them from organisms 
obtained  by  classical  mutagenesis  or  naturally.  In  the  case  of  microorganisms,  Bulgaria 
anticipates  that  additional  difficulties  will  arise  from  the  high  natural  variability  of  their 
genomes and the fast rates of evolution. 

Regarding  the  detection  of  GMMs  obtained  through  new  genomic  techniques,  the 
Commission  has  mandated  the  European  Union  Reference  Laboratory  for  Genetically 

57 Council Directive 90/219/EEC of 23 April 1990 on the contained use of genetically modified micro-organisms 
(OJ L 117, 8.5.1990, p. 1–14) – repealed. 

14 

 
 
 
 
 
 
 
 
 
                                                 
Modified  Food  and  Feed  (EURL)  to  prepare  together  with  the  European  Network  of  GMO 
Laboratories (ENGL), a report on the detection of genome edited microorganisms. 

The  Czech  Republic  and  Spain  noted  a  negative  impact  of  the  Court  ruling  on  research, 
development  and  innovation.  For  Spain,  the  authorisation  procedure  of  contained  use 
activities  involving  the  new  genomic  techniques  will  delay  their  implementation  by  EU 
researchers 
their 
competitiveness in terms of novelty in publications, technological transfer or patents. For the 
Czech Republic, projects  aiming at  developing  gene edited crops are not  realised because it 
would be practically impossible to place a new GMO on the EU market. 

those  from  other  countries.  This  will  reduce 

in  comparision 

to 

Finally,  the  Czech  Republic  and  France  noticed  also  an  impact  on  administrative  burden, 
respectively for the research scientists, and for the competent authority. France anticipates a 
10-  or  20-fold  increase  in  number  of  notifications  to  be  assessed  and  has  not  the  adequate 
resources to assess those. 

  Challenges 

Some  Member  States  pointed  out  some  legal  uncertainties  about  the  application  of  the 
Directive in the light of the Court ruling. 

First,  Bulgaria,  Ireland,  Luxembourg  and  Finland,  mention  that  the  basis  for  applying  the 
Court  ruling  to  the  Directive  needs  to  be  clarified  since  the  Court  based  its  decision  on 
Directive 2001/18/EC. Bulgaria considers that the definition of GMMs in the Directive, and 
of GMOs in Directive 2001/18/EC are practically identical, so any conclusions related to the 
definition  of  GMO  are  likely  be  relevant  with  the  necessary  changes  to  the  definition  of 
GMM.  

Bulgaria and Luxembourg underlined that the Directive does not have an equivalent to recital 
17  of  Directive  2001/18/EC,  which  excludes  organisms  obtained  through  certain  techniques 
of genetic modification that have conventionally  been used in a number  of applications  and 
have  a  long  safety  record.  Therefore,  for  Luxembourg,  clarification  is  needed  whether 
organisms generated through the new mutagenesis techniques are to be considered subject to 
the contained use Directive or not.  

In  addition,  Bulgaria  stressed  that  there  are  significant  differences  in  the  conditions  for 
exclusion of organisms from the scopes of each Directive. The exclusion criteria in Directive 
2009/41/EC are broader and include self-cloning. In the light of the Court ruling, according to 
Bulgaria,  it  will  seem  enough  that  the  criteria  of  Annex  II  part  A  are  fulfilled  to  exclude  a 
GMM from the scope of the Directive, without the necessity to demonstrate that the GMM is 
obtained by means of techniques/methods that have conventionally been used in a number of 
applications  and have  a  long safety  record. Under this interpretation,  some GMMs obtained 
by gene editing might be considered to be the result of self-cloning and thus outside the scope 
of the Directive.  

Germany  is  specifically  asking  if  self-cloning  using  new  molecular  techniques  (SDN3) 
continue  to  be  exempted  from  regulation  under  the  Directive.  Luxembourg  is  wondering,  if 
organisms that resemble those produced by self-cloning are outside the scope of the Directive 
as long as they are in contained use conditions, do these organisms become GMOs when they 
are not anymore under contained use.  

15 

 
 
 
 
 
 
 
 
 
 
The relevance of the Court ruling regarding the contained use of GMOs is unclear for some 
Member  States  (Bulgaria,  Ireland),  as  the  scope  of  the  Directive  covers  only  GMMs. 
Therefore,  when  national  legislations  were  extended  to  cover  GMOs,  it  is  not  clear  (for 
Bulgaria  and  Italy58)  if  the  contained  use  of  GMO  should  follow  Directive  2001/18/EC  or 
Directive 2009/41/EC, in particular with respect to the definition of GMO and the exclusion 
criteria. The Commission clarifies that Directive 2001/18/EC covers the deliberate release of 
GMOs  into  the  environment  and  their  placing  on  the  market.  Deliberate  release  means  any 
intentional introduction into the environment of a GMO or a combination of GMOs for which 
no specific containment  measures  are used to  limit  their contact  with  and to  provide  a high 
level  of  safety  for  the  general  population  and  the  environment.  Therefore,  Directive 
2001/18/EC does not cover the contained use of GMOs. 

Italy and Bulgaria would consider useful to extend the scope of the Directive to all GMO and 
to establish unified requirements for contained use of GM plants and animals.  

For  Germany,  the  Directive  seems  not  adequate  for  the  risk  assessment  of  genome-edited, 
self-cloned  organisms  resulting  from  SDN3  techniques  and  additional  questions  are  raised 
whether  the  application  of  certain  techniques  (CRISPR-Cas9  variants  like  dCas9  with  non-
functional  nuclease,  or  dCas13  variant  only  modifying  RNA)  lead  to  the  creation  of  GMO. 
Finland would like clarifications specifically in the context of deletion mutagenesis where no 
foreign  DNA  is  inserted  in  the  genome,  regarding  the  legal  status  of  the progeny  of  GMOs 
that do not inherit the modification, and on the legal status when an existing mutant organism 
is reverted to wild type using novel mutagenesis techniques. 

The  Netherlands  stated  that  the  Court  has  not  explained  what  constitutes  mutagenesis,  nor 
how to determine when mutagenesis techniques or methods have traditionally been used and 
have proven to be safe. This last point is also shared by Germany. 

Bulgaria and Finland would welcome clarifications from the Commission Legal Service. 

In this legally uncertain  situation, Finland reported that the Board for Gene Technology has 
made  a  non-consensus  interim  decision  that  contained  use  is  out  of  scope  of  the  Court’s 
ruling. The legal status of new mutagenesis techniques in contained use is currently evaluated 
by the Board on a case-by-case basis, as some variations of these techniques (e.g. gene drives) 
may result in GMOs. 

For  Bulgaria,  the  topic  of  new  genomic  techniques  shows  that  it  is  increasingly  difficult  to 
accommodate the developments of modern biotechnology by non-legislative means, and the 
possibility to amend or fully update the European GMO legislation should be considered.  

For the Netherlands, the Court’s ruling urges the legislator to keep the Directive up-to-date in 
respect  of  technical  and  scientific  progress,  and  it  is  urgent  that  the  scope  of  what  is  to  be 

58 Italy comment to the question “Has the scope of the transposing legislation been extended to the contained use 
of GM plants and GM animals in your Member State?”: “According to 2001/18/EC Directive, the contained use 
of  GMOs  (e.g.  for  testing/research  purposes)  should  be  carried  out  by  implementing  containment  measures 
based on the same principles as laid down in 90/219/EEC: it is not expected any notification to CAs. Contained 
uses of GMOs are non-regulated activities, both at EC and national levels.” 

16 

 
 
 
 
 
 
 
 
 
                                                 
understood by mutagenesis is clarified by authorities or the EU-legislator in order to provide 
clarity and legal certainty. 

Finland and the United Kingdom suggests to review the definition of genetic modification in 
the  Directive,  and  possibly  to  evaluate  the  pros  and  cons  of  technology-based  regulation 
versus trait-based regulation when dealing with a rapidly developing technology. 

Lithuania  remarked  that  it  would  be  helpful  to  have  information  on  risk  assessment 
methodology  and  safety  measures  to  use  for  each  new  genomic  technique,  and  would  also 
welcome harmonised EU legislation of new mutagenesis techniques. 

6.2 Other difficulties for interpretation of the Directive 

Some other issues for interpretation of the Directive related to its definitions: for example, for 
the  Czech  Republic,  whether  a  specific  sub-cellular  element  falls  under  the  definition  of 
“micro-organism” or not.  The Czech Republic considered that plasmids are not  GMOs, and 
that  a  DNA  vaccine  does  not  fall  under  the  scope  of  the  Directive  (although  during  the 
development  phase,  the  vaccinated  animals  should  be  treated  as  GMOs  until  appropriate 
studies prove that the plasmid DNA has not been integrated into the host genome).  

The  concept  of  “premises”  was  also  unclear  in  certain  cases,  and  unanticipated  needs  for 
moving  the  GMOs  temporarily  to  new  premises  for  non-repeating  procedures  (such  as 
photographing  or  scanning)  may  arise  quickly  in  research  laboratories,  which  can  cause  an 
administrative problem (Finland). 

the 
In  Germany,  some  regional  competent  authorities  encountered  problems  with 
interpretation  of  Annex  IV  of  the  Directive  and  suggested  a  more  precise  wording  of 
standards, while Slovakia would appreciate guidance regarding the isolation of the laboratory 
suite59. The Netherlands noted differences in interpretation of the Annexes between Member 
States.  

Bulgaria, Spain and Hungary reported difficulties regarding clinical trials (see part III, p. 20). 

6.3 Difficulties and solutions regarding the implementation of the Directive 

Many  Member  States60  have  no  further  difficulties  related  to  the  implementation  of  the 
Directive.  Aspects related to gene drive organisms are discussed in part IV of the report. 

 

Issues related to appropriate classification of the contained uses  

Finland indicated that the classification of viruses and cell cultures has been problematic in 
some  cases,  in  particular  when  pathogens  have  been  attenuated,  a  problem  faced  also  by 
Ireland. Sweden reported a problem to distinguish between class 1 and class 2 for GMM uses 
with  a  replication  deficient  virus  vector,  and  Denmark  mentioned  that  users  are  sometimes 
confused regarding the appropriate class for their laboratory work, in particular when working 
with adeno-associated virus vectors.  

59 “the laboratory is separated from other areas in the same building” (Annex IV, table I A, point 1). 
60 BE, BG, EE, EL, FR, HR, CY, LV, LT, LU, HU, MT, AT, PL, PT, RO. 

17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                 
Some Member States would consider useful that the Commission provides clarification on the 
classification  of  pathogenic  organisms  when  their  pathogenicity  has  been  attenuated 
(Finland),  establishes  a  list  of  known  biological  agents  in  accordance  to  the  hazards  and  in 
accordance with the classes of contained uses (Croatia), and more generally a list of generally 
regarded as  safe (GRAS) laboratory  strains,  laboratory animals  and cultivars adopted at  EU 
level, as those account for most of the activities done at universities and research institutions 
(Bulgaria).  

For  difficult  issues  and  cases  of  unclear  risk  assessment,  some  competent  authorities 
consulted specifically their advisory committee and/or other competent authorities under the 
Directive to know for example how attenuated viral vectors were classified in other Member 
States.  Ireland considered as a result of those consultations that attenuated lentiviral  vectors 
should be classified as class 2 GMMs.  

  Difficulties with notifications  

Regarding the assessment of notifications and the corresponding burden, the United Kingdom 
estimates that the time spent in reviewing lower-risk class 2 activities is disproportionate due 
to the amount of information required and the volume of class 2 notifications received (~90% 
of  notifications  are  for  class  2  uses),  and  Sweden  thinks  that  the  notification  procedure  for 
Class 1 and Class 2 is of limited value, and that the information required could be simplified. 
Two Member States (Denmark, Ireland) refer to issues for class 1 notifications, the procedure 
being time consuming, while those activities present no or negligible risk to the environment.  

The  Commission  clarifies  that  the  Directive  does  not  require  notification  of  subsequent 
activities for class 1 (Article 7 “Following the notification referred to in Article 6, subsequent 
class 1 contained use may proceed without further notification”). 

Germany and Slovakia reported difficulties for notification of class 3 contained uses (handling 
and inactivation of the organisms, several contained uses reported in one single notification). 
In case of premises that have been the subject of a previous notification to carry out a class 3 
or  4  contained  use,  Slovakia  considers  that  the  timeframe  of  45  days  for  the  competent 
authority to communicate its decision is too short (Article 9.2(a)).  

To  help  improving  the  situation,  some  Member  States  updated  their  procedures:  in  Ireland, 
users  are  not  required  anymore  to  submit  annual  reports  for  class  1  GMM  contained  use 
activities,  and  the  United  Kingdom  streamlined  its  notification  system  to  spend  less  time 
assessing class 2 activities. Regarding actions at national level, Denmark mentioned that class 
1 notifications could be taken out of the Danish legislation. 

Ireland  and  the  United  Kingdom  proposed  to  align  the  notification  requirements  with 
Directive  2000/54/EC  on  the  protection  of  workers  from  risks  related  to  exposure  to 
biological  agents  at  work61:  Ireland  suggests  the  alignment  for  class  1  GMM  contained  use 
activities , as that Directive does not require the notification of activities involving risk group 
1 biological agents; and the United Kingdom suggests the alignment for class 2 contained use 

61 Directive 2000/54/EC of the European Parliament and of the Council of 18 September 2000 on the protection 
of  workers from risks related to exposure  to biological  agents at  work (seventh individual directive  within the 
meaning of Article 16(1) of Directive 89/391/EEC) (OJ L 262 , 17/10/2000, p.21). 

18 

 
 
 
 
 
 
 
 
 
 
                                                 
activities, as that Directive requires only the first class 2 contained use at a given premises to 
be notified. Then, subsequent class 2 contained uses could be carried out, following approval 
by an internal safety committee, without the need to notify the national competent authority. 
Alternatively,  the  information  requirements  for  class  2  notifications  could  be  minimised. 
Sweden  also  suggested  that  less  information  could  be  provided  for  class  1  and  class  2 
contained  uses.  Sweden  noticed  that  Directive  2000/54/EC  is  currently  under  revision,  and 
wondered if, in case some safety measures in its Annexes V and VI would be changed, this 
would impact the containment measures in Annex IV of the Directive. 

Finland  suggested  a  simplification  in  the  notification  requirements  of  Article  6  when  the 
notifier is often changing premises.  

Slovenia suggests that inclusion of safe organisms in Part C of the Annex II of the Directive 
could contribute to reduce the size of the notifications, and the United Kingdom specifically 
refers to  the inclusion, by the Commission, of a list of multiply disabled vectors for class 1 
contained uses, which would provide greater delineation of class 1 and 2 contained uses and 
minimise the degree of over classification. 

  Other issues 

Two  Member  States  (Finland  and  the  Netherlands)  noted  issues  related  to  disinfectants:  the 
development of chemicals legislation has led to a situation where few effective disinfectants 
are available for pathogenic GMMs. Users in the laboratories are also poorly informed about 
the  suitable  disinfectants  currently  available  for  their  particular  GMMs,  and  sometimes  use 
disinfectants  that  have  not  (yet)  been  admitted  as  a  biocide  for  use  under  laboratory 
conditions. 
Here  the  Commission  notes  that  competent  authorities  should  intervene  when  seeing  that 
“Users in the laboratories are also poorly informed about the suitable disinfectants currently 
available for their particular GMMs, and sometimes use disinfectants that have not (yet) been 
admitted as a biocide for use under laboratory conditions.” 

Romania expressed a need and priority for further guidance on the risk assessment of living 
modified  (LM)  fish,  LM  organisms  produced  through  synthetic  biology,  LM  soil  dwelling 
organisms, and LM birds. 

Finally,  the  Netherlands  encountered  differences  in  the  strict  GMO-regulations  and  the  less 
strict  regulation  of  wild  type  pathogens,  which  could  partly  be  explained  by  the 
implementation  of  the  legislation  in  the  Netherlands,  but  seemed  also  caused  by  a  lack  of 
harmonisation at EU level. 

Some Member States managed to solve issues identified in the previous reporting period, for 
example,  by  asking  advice  to  their  scientific  advisory  bodies/experts.  Other  Member  States 
(Bulgaria,  Spain,  Lithuania,  Poland  and  Slovenia)  reported  communication  activities  to 
increase awareness and share best practices regarding contained uses activities among users, 
such as update of guidance documents, publication of brochures with examples of notification 
forms, and/or to engage with other experts to shared knowledge and experience. 

Italy, the Netherlands and Finland consider that discussions and/or actions at EU level might 
be helpful, for example on disinfectants, and more generally, a better cooperation among the 

19 

 
 
 
 
 
 
 
 
 
 
 
national competent  authorities and harmonised approaches at EU level (Italy), together with 
further training (Malta). 

PART II: OVERVIEW OF CONTAINED USES AND PREMISES 
Information on the number of notifications and amendments submitted for contained uses of 
GMMs,  number  of  premises  and  number  of  contained  uses  of  GMMs  reported  by  each 
Member State, are provided in the accompanying Commission Staff Working document. For 
those  Member  States  that  have  extended  the  scope  of  the  Directive  to  the  contained  use  of 
GM animals and GM plants62, information on the number of notifications for contained uses 
of GMOs submitted is also provided in the Commission Staff Working document. 

Table 1: Overview of authorised classes of contained uses in the Member States 

Class of use 

Number 
of MS 

No notifications  2 
2 
Class 1 only 
9 
Up to class 2 

Up to class 3 

11 

Up to class 4 

4 

Greece, Malta 
Bulgaria, Latvia 
Denmark , Croatia, Cyprus, Lithuania, Luxembourg, Hungary, 
Romania, Slovenia, Finland 
Belgium,  the  Czech  Republic,  Estonia,  Ireland,  Spain,  Italy,  the 
Netherlands, Austria, Poland, Portugal, Slovakia 
Germany, France, Sweden, the United Kingdom 

Of note, some Member States63 do not make distinction between GMM, GM plants and GM 
animals in notification procedures, therefore the data reported is a total of contained uses of 
GMMs and GMOs. 

The majority of the Member States64 that received notifications for GM plants or GM animals 
did not encounter specific challenges related to those. Still,  Poland reports challenges in the 
environmental  risk  assessment,  while  Sweden  estimates  there  could  be  difficulties  in  the 
future for assessing the risks, as there is no classification system for contained uses of GMOs 
and the assessment is case-by-case. 

PART  III:  INVESTIGATIONAL  MEDICINAL  PRODUCTS  THAT 
CONTAIN OR CONSIST OF GMOs 

1.  Notifications and authorisations for manufacturing and/or administration 

Eleven Member States authorise under the Directive the manufacturing and the administration 
of  investigational  medicinal  products  for  human  use  that  contain  or  consist  of  GMOs 
(Belgium, Greece65, France, Italy, Luxembourg66, Malta67, Austria, Poland, Portugal, Finland 
and the United Kingdom). Among those countries, only Belgium, France, Italy, Portugal (for 

62 All, except EE, EL, IT, CY, LV, LU, RO. 
63 DE, NL, UK. 
64 BE, IE, CZ, DK, FR, HR, HU, NL, AT, PT, SI, SK, UK. 
65 Manufacturing was auhorised only in 2018, administration authorised only in 2014-2017. 
66 Manufacturing was authorised only in 2014-2017. 
67 Only in 2018. 

20 

 
 
 
 
 
 
 
 
 
 
                                                 
manufacturing  only),  Finland  and  the  United  Kingdom  had  notifications  and  authorisations. 
The majority of those related to  Advanced Therapy Medicinal  Products  ("ATMPs"), mostly 
under class 1 and 2 of contained use (when specific information was known by the competent 
authority).  

Most of these Member States68 (except Malta and Poland, and with the addition of Slovenia69) 
also  authorise  manufacturing  and  administration  of  investigational  medicinal  products  for 
veterinary use, with very few notifications submitted and authorisations given.  

Some  other  Member  States  authorise  only  the  manufacturing  but  not  the  administration  of 
investigational  medicinal  products  under  the  Directive:  Bulgaria,  the  Czech  Republic, 
Germany,  Spain,  Hungary  and  Romania  for  human  and  veterinary  uses,  and  Ireland  for 
human  use  only.  One  Member  State  (Denmark)  authorises  only  the  administration,  and  not 
the manufacturing of those products (for both human and veterinary uses). 
Finally, eight Member States do not authorise the use of the products under the Directive, nor 
for  manufacturing,  nor  for  administration  (Estonia,  Croatia,  Cyprus,  Latvia,  Lithuania,  the 
Netherlands, Slovakia and Sweden). 

Table  2:  authorisation  of  investigational  medicinal  products  under  the  Directive,  and  total 
number of authorisations 

Human use 

Veterinary use 

BE 
BG 
CZ 
DE 
DK 
EE 
IE 
EL 
ES 
FR 
HR 
IT 
CY 
LV 
LT 
LU 
HU 
MT 
NL 
AT 
PL 
PT 

Manufacturing 
Yes / 10 
Yes / 0 
Yes / 0 
Yes / N.D 
No 
No 
Yes* / 0 
Yes* / 0 
Yes */ N.D 
Yes / 5 
No 
Yes / 11 
No 
No 
No 
Yes* / 0 
Yes* / 0 
Yes* / 0 
No 
Yes / 0 
Yes / 0 
Yes / 3 

Administration 
Yes / 66 
No 
No 
No 
Yes / 12 
No 
No 
Yes* / 0 
No 
Yes / N.D 
No 
Yes / 51 
No 
No 
No 
Yes / 0 
No 
Yes* / 0 
No 
Yes / 0** 
Yes / 0 
Yes / 0 

Manufacturing 
Yes / 0** 
Yes* /0 
Yes / 0 
Yes / N.D 
No 
No 
No 
Yes / 0 
Yes * / N.D 
Yes / N.D 
No 
Yes / 0 
No 
No 
No 
Yes / 0 
Yes* / 10 
No 
No 
Yes / N.D 
No 
Yes / 0 

68 For Greece and France: administration was authorised only in 2014-2017. 
69 Manufacturing and administration only in 2018.  

Administration 
Yes / 2 
No 
No 
No 
Yes* / 0 
No 
No 
Yes* / 0 
No 
Yes* / N.D 
No 
Yes / 0 
No 
No 
No 
Yes / 0 
No 
No 
No 
Yes / N.D 
No 
Yes / 0 

21 

 
 
 
 
 
 
 
 
                                                 
 
RO 
SI 
SK 
FI 
SE 
UK 

Yes* / 0 
No 
No 
Yes / 7 
No 
Yes / N.D 

No 
No 
No 
Yes / 13 
No 
Yes / N.D 

Yes* / 0 
Yes* / 0 
No 
Yes / 0 
No 
Yes / N.D 

No 
Yes* / 0 
No 
Yes / 0 
No 
Yes / 1 

* indicates that only in one period (either 2014-2017, or 2018), the Member State’ reply was “yes”. 
** some notifications were submitted but 0 authorisation. 
N.D: not determined 

2. 

Challenges regarding the manufacturing activities 

The majority of Member States report no specific challenges (or no relevance as this activity 
is  not  taking  place)  in  implementing  the  Directive  for  the  manufacturing  of  investigational 
medicinal products that contain or consist of GMOs for human or veterinary uses.  

Belgium noticed that in  some cases the manufacturing of investigational medicinal products 
has been made in another country and wonder to what extent all the data need to be checked. 

Several  Member  States  (Belgium,  Germany,  Italy  and  Finland)  mentioned  that  different 
(control) authorities can be involved in data package evaluation, authorisation, and control of 
the activity/premises, and this can be challenging. It is suggested (Finland) that the interplay 
of  contained  use,  good  manufacturing  practice  (GMP),  occupational  safety  (protection  of 
workers from exposure to biological agents), and the Access and Benefit Sharing Regulation70 
is clarified, to avoid unnecessary regulatory burden for the operators and authorities involved. 

Regarding veterinary use, in case of challenges, they are not different compared to the ones 
reported for human use, just Finland notes that it is more difficult to find national experts on 
the  risk  assessment  for  veterinary  use.  Finland  suggests  forming  a  network  of  experts  that 
competent authorities could refer to when needed.  

Some  Member  States  (Belgium,  Italy  and  Poland)  proposed  increased  cooperation  and 
information sharing among Member States, and among experts involved in the evaluation of 
different aspects of the medicinal products (safety, biosafety, quality).  

3. 

Challenges regarding the administration activities 

Regarding the administration of investigational medicinal products for human use that contain 
or consist  of GMOs,  Finland and  Italy  report that  the submission  of notifications in  case of 
multicentre clinical trials is challenging. The concept of "notifier" (company developing the 
product, the CRO (contract research organisation), the hospital, etc.) is not always clear, and 
further  sharing  of  information  between  the  different  actors  involved  is  needed  so  that  the 
notification is complete. In addition, Finland notes that challenges can arise from the interplay 
of  various  regulations  concerning  GMOs,  pharmaceuticals,  occupational  safety,  waste 
treatment, and patient rights. 

70  Regulation  (EU)  No 511/2014  of  the  European  Parliament  and  of  the  Council  on  compliance  measures  for 
users from the Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits 
Arising from their Utilization in the Union 

22 

 
 
 
 
 
  
 
 
 
 
                                                 
Belgium, Bulgaria, Spain, France, Italy, Hungary, Portugal, Romania, Finland and Sweden71 
underline the difficult distinction between contained use or deliberate release for clinical trials 
with  GMOs,  and  the  fact  that  Member  States  have  different  interpretations  and  approaches. 
This  creates  difficulties  for  the  competent  authorities,  and  also  for  companies  and  users,  in 
particular in case of clinical trials in different countries (with then different requirements). 

For example, for Spain, it is not clear whether facilities in which GMOs are handled or stored 
must  be  notified  for  contained  used  activities.  In  Sweden,  only  preparations  and  sample 
analysis may be notified as contained use, and this can create confusion for the users (which 
part of an activity is contained use, and which part is not). For Bulgaria, it is not clear how the 
provisions of the Directive should be applied when GMM is administered in hospital during 
clinical  trial but  the patients  are not  kept under  contained conditions  for the duration of the 
trial. 

For Italy, it is also a challenge to establish the relevant cases for which a risk assessment has 
to be submitted by a notification or not, if a medicine used in the clinical trial has obtained the 
marketing authorisation by EMA centralized procedure. In these cases, the risks to consider 
could be different for a new clinical trial if compared to those assessed in order to obtain the 
marketing authorisation.  This last aspect need to  be assessed on a case by case basis by the 
Italian competent authority. 

The  Commission  specifies  that  clarification  about  the  authorisation  under  the  GMO 
framework  in  case  of  clinical  trials  with  investigational  products  that  have  a  marketing 
authorisation has been given in the document “Medicinal products for human use containing 
or  consisting  of  GMOs:  interplay  between  the  EU  legislation  on  medicinal  products  and 
GMOs – Frequently asked questions”72. 

Regarding  the  administration  of  investigational  medicinal  products  for  veterinary  use  that 
contain  or  consist  of  GMOs,  further  specific  comments  relate  to  the  difficulty  to  assess  if 
notifications are for clinical trials or for research and development (Belgium), to the fact that 
risk management methods are challenging if the test subjects are pets or companion animals 
(Finland). Sweden reports that a future challenge may be a clinical trial with caged animals.  

Some  solutions  have  been  implemented  at  national  level.  In  Sweden,  respective  competent 
authorities  collaborate  to  help  the  users.  When  the  framework  to  be  followed  is  not  clear, 
Belgium  recommends  applicants  to  request  advice  from  the  Federal  Agency  for  Medicines 
and Health Products  prior to  the submission  of the clinical  trial application.  In addition,  the 
competent  authority,  in  collaboration  with  the  Belgian  federal  agency  for  medicines,  is 
preparing  a  document  “guideline”  aiming  to  help  applicants  in  determining  the  regulatory 
procedures they must follow. Germany reported that an administrative agreement was reached 
in  March  2015  between  the  relevant  federal  and  competent  authorities  regarding  the 
distinction  between  genetic  engineering  activities  in  containment  and  approval  of  clinical 
trials  with  GMOs.  In  the  United  Kingdom,  the  competent  authority  is  discussing  with  the 

71 Spain and Sweden regulates clinical trials with GMOs as deliberate release activities. In Belgium, depending 
on the characteristics and mode of administration of the medicinal product, it is possible that clinical trials with 
GMOs medicinal products for human use do not require an authorisation under the deliberate release Directive. 
Bulgaria and Portugal define the legal framework of the GMOs clinical trial on a case-by-case basis, taking into 
account the specificity of the GMO clinical trial.  
72 Available at: https://ec.europa.eu/health/human-use/advanced-therapies_en  

23 

 
 
 
 
 
 
 
 
                                                 
medicines regulator to see if there are ways to streamline clinical trials whilst complying with 
requirements under the different regimes. 

However,  various  Member  States  stressed  that  addressing  issues  related  to  the  legal 
framework  for  clinical  trials  with  GMMs  should  be  done  at  EU  level.  France  and  Portugal 
would welcome clarifications on the legislative framework to be applied. Spain would like to 
have harmonised guidelines at EU level in order to clarify whether clinical trials have to be 
carried  out  under  the  scope  of  the  Directive  or/and  of  the  Directive  2001/18  /EC.  Bulgaria, 
Spain, Italy and Portugal consider that there should be a harmonisation of the procedures for 
the notification and evaluation of clinical trials with GMMs at EU level (and also of guidance, 
for Portugal). In addition, the notification process should be improved and simplified for Italy, 
which  suggests  amending  the  Directive  and  Directive  2001/18/EC  with  ad  hoc  provisions 
focused on clinical trials in which investigational medicinal products (IMPs) are administered. 
Finally,  for  Italy,  a  harmonised  approach  at  EU  level  would  allow  the  Commission  and 
Member  States  to  be  informed  about  clinical  trials  authorised  under  the  Directive  and  to 
publish the relevant information on the Commission website. 

Bulgaria, Italy, Finland and the United Kingdom expect that the Ad-hoc working group on the 
interplay between the GMO legislation and the legislation on medicinal products will clarify 
the  situation  of  clinical  trials  with  GMMs,  through  provision  of  better  information  and 
guidance on risk assessment of certain types of vectors etc.  

The Ad-hoc working group on the interplay between the GMO legislation and the legislation 
on  medicinal  products  was  set  up  as  a  result  of  demands  from  Member  States'  competent 
authorities  and  stakeholders  to  address  a  number  of  issues  relating  to  the  interplay  between 
the  GMO  legislation  and  the  legislation  on  medicinal  products,  with  the  objective  to  seek 
practical ways to address the identified issues within the existing regulatory framework. 

Finland  also  suggests  examining  whether  GMO  medicinal  product  production  and  clinical 
trials should be legally separated from GMO directives.  

PART IV: GENE DRIVE MODIFIED ORGANISMS 

1.  Notifications and measures taken regarding gene drive modified organisms 

Three  Member  States  (Germany,  France73  and  Italy)  reported  notifications  for  gene  drive 
modified organisms (GDOs)74 submitted under their contained use legislation: on Drosophila 
melanogaster  for  basic  research  (class  1  –  Germany),  on  Anopheles  gambia  and  Anopheles 
arabiensis for the development of GM mosquitoes for malaria control (class 2 – Italy). 

In  addition,  some  Member  States  (Germany,  France75,  the  Netherlands,  Sweden  and  the 
United  Kingdom)  took  measures  regarding  GDOs  under  the  Directive,  involving  their 
advisory board for scientific guidance, or by amending their procedures. 

73 France did not report additional information about the received notifications. 
74  For  the  purpose  of  this  report,  the  definition  of  "gene  drive"  is  a  system  of  biased  inheritance  in  which  the 
ability of a genetic element to pass from a parent to its offspring through sexual reproduction is enhanced. 
75 France did not report additional information about the measures taken. 

24 

 
 
 
 
 
 
 
 
 
 
 
                                                 
More  notably,  Germany  involved  its  advisory  board,  which  issued  a  position  statement 
according to which activities generating GDOs are classified as class 2. The recommendation 
of specific safety measures will be done by the advisory board on a case by case assessment. 
Germany also provided details about the specific containment measures implemented for the 
contained use of gene drive modified Drosophila to prevent their escape. 

The Netherlands amended their GMO contained use legislation: it requires for all applications 
for  GDOs  a  permit  instead  of  a  notification.  Their  national  legislation  allows  for  imposing 
specific  containment  measures  on  top  of,  or  as  an  alternative  for,  the  general  containment 
measures. 

Sweden differentiates the contained use of GDOs according to the type of the organism. If a 
GMM  would  be  modified  with  a  gene  drive  mechanism,  it  should  be  at  least  considered  as 
class 2, with a specific risk assessment (focus on the risks in case of unintended release of the 
GMM).  For  GM  animals,  the  notification  form  will  be  amended  if  there  will  be  future 
notifications concerning gene drive animals. 

The  competent  authority  of  the  United  Kingdom  issued  guidance  on  gene  editing  and  gene 
drive  (prepared  by  its  scientific  advisory  committee)  to  advise  users  of  configurations  of 
CRISPR Cas9 that would raise concerns.  

2.  Possible challenges regarding the contained use of gene drive modified organisms 

Various  Member  States  reported  that  their  experience  with  contained  use  of  GDOs  is 
relatively limited and some anticipate possible challenges. 

First,  regarding  the  scope  of  the  Directive,  Bulgaria,  Finland,  Italy,  Sweden  and  the  United 
Kingdom noted that the vast majority of potential GDOs are likely to be animals (insects and 
rodents)  and  plants.  Therefore,  they  would  be  outside  of  the  scope  of  the  Directive,  which 
covers only GMMs, and would not require a notification76. Sweden is of the opinion that the 
issue  may  be  more  relevant  for  the  Directive  2001/18/EC  (since  gene  drive  concerns 
eukaryotic organisms).  

The United Kingdom explained that it is difficult to regulate GDOs under the Directive, even 
if GM plants and animals  are included in  its national  legislation (as  in  many other Member 
States)  because  there  are  no  activity  notification  requirements  (or  class  of  work)  for  GM 
plants/ animals. For Finland, additional legal measures may be necessary for Member States 
that  only  regulate  GMMs  in  their  national  contained  use  legislation,  while  for  Bulgaria, 
harmonisation  of  requirements  for  contained  use  of  GDOs,  other  than  gene  drive  modified 
micro-organisms, between Member States is an open issue. 

Regarding the risk assessment and  risk management of those organisms, Belgium, Bulgaria, 
Ireland,  Italy,  Lithuania,  the  Netherlands,  Romania,  Finland  and  Sweden  anticipate  possible 
challenges,  in  particular  for  environmental  risk  assessment,  correct  classification  and 
appropriate containment measures. 

76  The  Commission  notes  that  if  a  Member  State’  national  legislation  has  been  extended  to  GM  animals  and 
plants, a notification will be required. 

25 

 
 
 
 
 
 
 
 
 
 
 
                                                 
Italy  reported  difficulties  as  no  specific  provisions  are  laid  down  in  the  Directive  for  the 
contained use of GDOs. The Netherlands also underlined that the classification system of the 
Directive  and  the  corresponding  containment  measures  focus  on  the  pathogenicity  of  the 
GMM,  while  the  biology  of  GDOs  may  require  different  containment  measures.  Belgium 
noted in particular the specific characteristics of the GDOs to be considered, such as the rapid 
spread  of  the  carried  modification  through  several  generations  of  target  or  non-target 
organisms and the potential risks for the environment (while in general the GDO will not be 
pathogenic).  

Some  Member  States  stressed  the  importance  of  a  case-by-case  approach,  even  more  as 
different groups of GDOs have different reproductive and ecological characteristics (Belgium, 
Bulgaria, Italy).  

Finland  also  noticed  that  if  the  user  has  already  an  existing  notification  for  class  1  use,  it 
could start a new class 1 activity without a new notification, and if the user has classified the 
GDO in the risk assessment into class 1, the competent authority would not be informed about 
such activity with GDO before an inspection of the premises. 

Belgium, Italy, the Netherlands and Sweden noted that some adaptations should be considered 
for GDOs (additional requirements, higher containment level and control measures) to ensure 
that performed activities with those organisms can be considered safe for the humans, animals 
and  environment.  Still,  for  Belgium,  and  Sweden,  a  proper  risk  assessment  (case-by-case 
procedure)  will  catch  possible  risk  with  such  GMMs  and  the  Directive  remains  appropriate 
for the protection of the environment and workers for contained use of gene drive modified 
micro-organisms. 

Bulgaria  mentioned  that  it  may  be  appropriate  to  consider  initially  that  any  GDO  will  pose 
high  risk  for  the  environment  and  to  apply  stringent  containment  measures.  Such  measures 
should  use  at  least  two  different  containment  strategies  suitable  for  the  specific  modified 
organism.  

The  United  Kingdom  highlighted  that  there  is  a  lack  of  consistency  in  the  approach  across 
Member States with regard to activities with GDOs.     

More  broadly,  several  Member  States  (Spain,  France,  Italy,  Lithuania,  Hungary,  the 
Netherlands, Poland and Finland) suggested to have discussion and exchange of information 
at  EU  level,  on  experience  and  activities  with  GDOs  under  contained  use.  They  would 
welcome  harmonised  guidelines  at  EU  level  regarding  procedure  for  GDOs  including 
notification,  risk  assessment  methodology,  containment  measures  and  control  requirements. 
This could possibly result in an amendment of the Directive (Italy, the Netherlands). 

Finally,  Bulgaria  and  the  Netherlands  mention  that  GDOs  could  move  across  borders,  and 
therefore  it  is  important  for  those  countries  to  establish  mechanisms  for  fast  and  effective 
cooperation  between  Member  States  if  such  organisms  are  released  into  the  environment, 
deliberately77  or  accidentally.  The  Netherlands  would  welcome  an  EU  guidance  on  how  to 
inform Member States in case of a high-risk incident with GMM or GMO, which should be 
explicitly extended to GDOs. 

77 The Commission notes that the Directive 2001/18/EC applies in case of deliberate release in the environment 
of GMOs. 

26 

 
 
 
 
 
 
 
 
                                                 
SUMMARY AND CONCLUSIONS 

Member States reported their experience with  the Directive for the period 2014-2018 to  the 
Commission. This report summarises those contributions (available in the Annex) and covers 
notification  and  approval  systems,  risk  assessment  and  classification  of  contained  uses, 
accidents, inspection and enforcement issues, and implementation of the Court ruling on new 
mutagenesis techniques, for the contained use of GMMs.  

Some  clarifications  from  the  Commission  are  also  added  in  this  report,  to  address  Member 
States’ comments. 

It  should  be  noted  that  the  vast  majority  of  Member  States  has  extended  the  scope  of  their 
transposing  legislation  to  the  contained  use  of  GM  plants  and  GM  animals,  and  in  some 
countries,  the  transposing  legislation  is  stricter  than  the  Directive  (notifications  for  Class  1 
contained uses, waste inactivation for all classes). 

Few  Member  States  reported  changes  regarding  the  notification  and  approval  systems  as 
compared to the period 2009-2014. During period 2014-2018, most Member States processed 
the  notifications  within  the  statutory  timeframe.  When  delays  occurred,  they  concerned 
usually less than 15% of the assessed notifications and Member States took actions to reduce 
and prevent such delays. However, many noted the increasing complexity of the notifications, 
which  makes  the  processing  time  longer.  Member  States  reported  difficulties  related  to  the 
quality  and  completeness  of  the  submitted  notifications,  and  difficulties  linked  to  the 
definitions  of  the  Directive  and  the  correct  classification  of  the  contained  uses.  They  also 
stressed the administrative burden of the notification system. Some Member States suggested 
changes in the Directive, for example to review the definition of genetic modification in the 
Directive, or amending the notification requirements for class 1 and 2 of contained uses. 

Regarding waste, in some Member States the waste from contained use activities is recycled 
after inactivation. Inspection procedures put in place by the Member States included regular 
inspections to evaluate in particular the compliance with the Directive, the correctness of the 
risk  assessment  classification,  the  effectiveness  of  the  respective  containment  level.  The 
number of inspections  carried out  during the reporting period varies among Member States, 
from 10 to 100% of the premises controlled. Very few Member States reported accidents, or 
some  incidents.  In  general,  when  public  consultations  are  carried  out,  no  comments  are 
submitted. In several Member States, information on the premises for contained use of GMMs 
and GMOs is maintained updated and available online. 

The  national  reports  show  an  emphasis  on  increased  communication  between  users  and 
competent authorities, to increase awareness and share best practices regarding contained uses 
activities among users. 

While many Member States reported no specific difficulties regarding the interpretation of the 
Directive,  those  that  reported  issues  often  refer  to  problems  with  the  definition  of 
GMMs/GMOs in the context of new genomic techniques, and synthetic biology.  
Member States are receiving notifications for contained use of GMMs/GMOs obtained with 
new mutagenesis techniques. Regarding the impact of the Court ruling on new mutagenesis, a 
number  of  countries  indicated  that  it  has  no  impact  as  risk  assessment  and  management  of 

27 

 
 
 
 
 
 
 
 
 
 
contained uses of GMMs and GMOs obtained by new techniques are performed in the same 
way  as  other  GMOs.  On  the  other  hand,  some  Member  States  mentioned  difficulties  in 
applying  and  enforcing  the  contained  use  legislation  for  GMOs  obtained  through  new 
genomic techniques due to their detection and identification, and the difficulty to distinguish 
them  from  organisms  obtained  by  classical  mutagenesis  or  naturally.  A  few  Member  States 
pointed out some legal uncertainties about the application of the Directive in the light of the 
Court ruling. 

There  are  also  differences  among  Member  States  regarding  the  manufacturing  and 
administration of investigational medicinal products for human or veterinary use that contain 
or  consist  of  GMOs.  Some  Member  States  authorise  one  or  both  activities 
(manufacturing/administration)  under  the  Directive  while  others  do  not.  The  difficult 
distinction between contained use or deliberate release for clinical trials with GMOs, and the 
fact  that Member States  have different  interpretations  and approaches, create difficulties for 
the competent authorities, and also for companies and users.  

Various  Member  States  stressed  that  addressing  issues  related  to  the  legal  framework  for 
clinical  trials  with  GMMs  should  be  done  at  EU  level  and  some  expect  that  the  Ad-hoc 
working group on the interplay between the GMO legislation and the legislation on medicinal 
products  will  clarify  the  situation  of  clinical  trials  with  GMMs,  through  provision  of  better 
information and guidance on risk assessment of certain types of vectors etc.  

Regarding  gene  drive  modified  organisms,  only  few  Member  States  reported  notifications 
submitted under their contained use legislation, for basic research or for the development of 
GM  mosquitoes  for  malaria  control.  Some  Member  States  took  measures  regarding  GDOs 
under  the  Directive,  involving  their  advisory  board  for  scientific  guidance,  or  by  amending 
their  procedures.  Various  Member  Sates  anticipated  possible  challenges,  in  particular  for 
environmental risk assessment, correct classification and appropriate containment measures of 
GDOs. Some also pointed out difficulties to regulate GDOs under the Directive, even in cases 
where the national transposing legislation has been extended to cover GM plants and animals.  

For some Member States, additional legal measures and/or harmonisation may be necessary 
between Member States, in particular for the ones that only regulate GMMs in their national 
contained use legislation. Several Member States consider that it might be helpful to exchange 
information  on  experience  and  activities  with  GDOs  under  contained  use.  They  would 
welcome  harmonised  guidelines  at  EU  level  regarding  procedure  for  GDOs  including 
notification, risk assessment methodology, containment measures and control requirements. 

More broadly, there is a need for better cooperation among the national competent authorities 
and harmonised approaches at EU level in relation with the interpretation and implementation 
of the Directive. 

28