REPORT FROM THE COMMISSION on the 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 2019 – 2021
Date: 2023-02-15
Institutions: Directorate-General for Health and Food Safety, European Commission
Subjects: EU Member State, application of EU law, clinical trial, environmental protection, environmental risk prevention, genetically modified organism, medicinal product, public health

EN 

  EN 

   EUROPEAN COMMISSION  Brussels, 15.2.2023  COM(2023) 75 final  REPORT FROM THE COMMISSION on the 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 2019 – 2021  
 
 
Table of Contents 
INTRODUCTION ...................................................................................................................... 2 

PART I: GENERAL IMPLEMENTATION OF THE DIRECTIVE ......................................... 4 

1.  Notification and approval systems (and relevant changes) ............................................. 4 

2.  Waste disposal ................................................................................................................. 4 

3. 

Inspection and enforcement issues .................................................................................. 5 

4.  Accidents ......................................................................................................................... 7 

5.  Public consultation .......................................................................................................... 8 

6. 

Interpretation of the Directive ......................................................................................... 8 

7.  Overview of contained uses and premises .................................................................... 10 

PART II: INVESTIGATIONAL MEDICINAL PRODUCTS THAT CONTAIN OR 
CONSIST OF GMOs ............................................................................................................... 11 

PART III: GENE DRIVE MODIFIED ORGANISMS ............................................................ 13 

CONCLUSIONS ...................................................................................................................... 14 

 
 
 
 
 
Report on the 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 2019 – 2021 

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  Council  on  the  contained  use  of 
genetically modified micro-organisms1 (GMMs). 

INTRODUCTION 

Directive 2009/41/EC ("the Directive") provides that every three years Member States  are to 
send to the Commission a summary report on their experience with the Directive2 and that the 
Commission  is  to  publish  a  summary  based  on  these  reports3.  The  Commission  has  so  far 
published  five  reports  pursuant  to  the  Directive  or  to  the  preceding  Council  Directive 
90/219/EEC4, for the periods 1999-2003, 2003-2006, 2006-2009, 2009-2014 and 2014-20185. 

The present report covers the period from January 2019 to December 2021 and is based on 26 
Member States6' and two EEA EFTA States7’ individual reports. 

The  national  reports  are  based  on  a  questionnaire  prepared  by  the  Commission  services  on 
Member States’ experience with the general implementation of the Directive, including their 
notification  and  approval  systems,  inspection  and  enforcement  activities,  waste  disposal 
measures, accidents, public consultation and an overview of contained uses and premises for 
GMMs authorised in their territories. 

The Directive does not regulate the contained use of GMOs other than GMMs, e.g. GM plants 
and GM animals8. However, in a number of Member States, the relevant national legislation 
regulates the contained use of GMOs as well. Therefore, the Commission extended the scope 
of  its  questionnaire  to  allow  Member  States  to  share  their  experience,  good  practices  and 
challenges encountered in regulating also those organisms. 

The  report  focuses  on  changes  from  previous  reports  and  highlights  new  issues  and 
implementing  challenges  raised  by  Member  States  and  the  way  they  were  addressed.  It 

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 Malta has not provided a national report.  
7 Annex XX to the EEA Agreement (which lists, amongst others, the EU GMO legislation applicable under that 
Agreement) provides that ‘[f]or the purposes of this Annex and notwithstanding the provisions of Protocol 1, the 
term  "Member  State(s)"  contained  in  the  acts  referred  to  shall  be  understood  to  include,  in  addition  to  its 
meaning  in  the  relevant  EC acts,  Iceland,  Liechtenstein, Norway’.  Therefore,  reference  to  ‘Member  States’  in 
this document also includes the EEA EFTA States who replied to the questionnaire (Norway and Iceland). 
8 Article 2(4), second indent of Directive 2001/18/EC on the deliberate release of GMOs into the environment 
excludes  from  the  definition  of    ‘placing  on  the  market’  ‘making available  GMOs  other  than  microorganisms 
referred  to  in  the  first  indent,  to  be  used  exclusively  for  activities  where  appropriate  stringent  containment 
measures are used to limit their contact with and to provide a high level of safety for the general population and 
the environment, the measures should be based on the same principles of containment as laid down in Directive 
90/219/EEC’. 

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provides, in the conclusions, the Commission’s views on some questions raised by Member 
States regarding the implementation of the Directive.  

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. 

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PART I: GENERAL IMPLEMENTATION OF THE DIRECTIVE 

1.  Notification and approval systems (and relevant changes) 

No  major  changes  since  the  last  reporting  period  were  reported  concerning  the  competent 
authorities responsible for applying the national legislation or in the legislation. 

Germany  reported  changes  in  its  national  legislation  to  extend  its  notification  and  approval 
system  to  gene  drive  organisms  and  to  keep  up  to  date  the  level  of  academic  expertise  and 
knowledge of biological safety officers and project leaders.  

France  prepared  new  application  forms  including  a  dedicated  section  on  new  genomic 
techniques. Before the publication of the new forms, French authorities supported applicants 
in  filling  out  application  forms  concerning  contained  uses  of  GMOs  obtained  using  such 
techniques.  

Some  Member  States  reported  challenges  in  the  notification  and  approval  process.  Those 
were  related  to  the  time  limits  for  processing  notifications  and  following  the  administrative 
procedures, as well as to the complexity of some notifications. 

Austria reported challenges related to the timely processing of a particular notification which 
required  assessing  a  microwave  technology  for  the  inactivation  of  waste  from  class  2 
contained uses. This notification required a time-consuming risk assessment and collaboration 
with the national scientific committee prior to approval. 

Slovenia reported an increase in workload, particularly for biosafety class 2 notifications, due 
to  a  higher  number  of  notifications,  which  almost  doubled,  as  well  as  to  the  COVID-19 
pandemic,  since  many  research  institutions  started  research  projects  on  the  SARS-CoV-2 
virus.  These  developments,  together  with  the  lengthy  administrative  procedures  of  the 
national scientific committee, led to delays in processing notifications. 

Italy  highlighted  the  need  for  appropriate  digital  tools  to  reduce  the  staff  workload,  and 
provided  an  example  of  a  collaboration  project  between  the  supervisory  and  safety  bodies, 
research institutions and hospitals, to increase the knowledge and skills for the prevention of 
risks  and  the  protection  of  health  and  the  environment  as  regards  the  contained  use  of 
GMMs9. 

Denmark  reported  the  presence  of  antibiotic  resistance  marker  genes  as  a  challenge  in  the 
approval process and the authorities’ efforts to phase out GMO strains containing such genes 
which are used to produce medicines. The competent authority is currently setting up different 
criteria for approval of the presence of these types of genes, one of which is to identify what 
antibiotic the gene confers resistance to, as categorised by the European Medicines Agency.  

2.  Waste disposal 

In  general,  the majority  of Member States  reported neither changes nor  challenges  in  waste 
management during the reporting period. 

Belgium reported on a new waste regulation at regional level (Brussels Capital Region). 

9 The tool for creation of the network is the website www.biotechsafety.org 

4 

 
                                                 
 
Germany  reported  an amendment  of the  national  legislation  clarifying the rules on  in-house 
transport  of  GMO  waste.  In  particular,  it  now  requires,  as  from  safety  level  1,  that  the 
transport of this waste takes place in labelled, sealed and shatterproof containers that can be 
disinfected. 

Austria  and  Finland  reported  challenges  in  the  assessment  of  alternative  methods  of  GMM 
inactivation. 

Austria reported ongoing discussions on the use of a microwave waste inactivation system as 
an alternative to autoclaving for the inactivation of class 2 GMO waste, with exceptions for 
certain types of viruses and biosafety levels. 

Austria considered that general EU guidelines or an official checklist of requirements would 
be useful to aid the evaluation and approval process for alternative inactivation methods in the 
future. This guideline could, for example, include a list of inactivation parameters according 
to which any new inactivation method should be validated (test parameters, test organisms for 
different  biosafety  levels  and  groups  of  organisms,  whether  direct  comparison  with  the 
standard autoclaving method is required, etc.). 

Finland  reported  that  few  research  institutes  are  willing  to  maintain  in  situ  autoclaving 
facilities  because  of  their  costs  and  occupational  health  issues.  In  addition,  Finland  and 
Germany  noted  that  operators  find  fewer  disinfectants  on  the  market  suitable  for  chemical 
inactivation  of  their  GMMs.  Therefore,  most  operators  prefer  to  send  their  GMM  waste  to 
municipal  incineration  plants,  but  there  are  difficulties  with  waste  packaging  and 
transportation  requirements  (labelling,  classification,  etc.).  Finland  considered  that  the 
relevant  EU  requirements  are  very  complex  and  ambiguous  when  it  comes  to  non-infective 
GMMs that are not pathogens. The competent authority is tackling this issue by giving advice 
to operators on a case-by-case basis considering the different sectoral requirements. 

In addition, Finland reported its experience with recycling of class 1 microbial fermentation 
waste together with  other bio-waste into compost, which required studies on  the survival  of 
GMMs  and  monitoring  to  confirm  that  the  composting  process  worked  effectively  and  no 
GMMs survived it. 

3.  Inspection and enforcement issues 

The  majority  of  Member  States  reported  no  changes  in  their  inspection  and  enforcement 
activities. 

Belgium, Czech Republic, Denmark, Germany, Spain, Finland, Portugal and Norway reported 
changes in this field, in several cases due to the COVID- 19 pandemic.   

Those Member States established digital tools and reported a wide use of instruments for the 
remote  surveillance  of  activities  and  facilities,  for  example  video  conferences  with  virtual 
tours,  questionnaires,  presentation  of  photographs,  reports,  recordings  and  maintenance 
protocols. However, Austria and Italy reported a lack of reliable and appropriate digital tools 
for remote inspections. Portugal adopted a guidance to support inspectors. 

Some Member States reported shortages in disinfectants due to the COVID-19 pandemic. 

Overall,  the  number  of  inspections  varied  between  Member  States  from  6%  to  100%  of 
contained use premises.  

5 

 
A few countries10 did not carry out any inspection during the reporting period, mostly because 
no contained use premises/activities were notified and, in some cases, due to the COVID-19 
pandemic, particularly during the lockdown period11.  

In  general,  the impact  of  the COVID-19 pandemic on inspection  and enforcement  activities 
resulted in: 

  a decrease in the number of on-site inspections, particularly for class 1 contained uses 

(Belgium, Ireland); 

  changes  in  the  way  inspections  were  carried  out  in  some  Member  States,  such  as  a 
switch  to  remote  or  hybrid  inspections  (Germany,  Finland);  in  many  cases  remote 
inspections  were  focused  primarily  on  keeping  mandatory  documentation  checks 
(Czech Republic); 

  application  of  risk-based  criteria  for  remote  inspections,  modification  of  inspection 

plans (Czech Republic and Denmark). 

Some  Member  States  acknowledged  that  remote  inspection  is  an  effective  way  to  inspect 
laboratories performing low risk work. It saves the inspectors time as well, which gives them 
more time for assessing uses with higher risk to the environment and health. 

The  issues  most  frequently  encountered  in  the  course  of  inspections  reported  by  some 
Member States12 were related to deficiencies in: 

  compliance  with  good 

laboratory  practice  (GLP)  as  regards  premises  (e.g. 
organisation,  inadequacy  or  deficiencies  in  laboratory  equipment,  incorrect  labelling 
of the laboratory and equipment), or users (e.g. inadequate protective clothing, missing 
instructions, insufficient training); 

  biosafety measures (e.g. no restricted access to the premises where the contained use 
takes place, level of protection not corresponding to the risk class, insufficient hygiene 
and  disinfection  methods)  and  internal  control  procedures  (e.g.  lack  of  a  biosafety 
officer  in  charge  of  implementing  properly  the  confinement  and  control  measures 
according to the class of risk); 

 

the  administrative  procedures  (delayed  notification  of  changes  in  persons  in  charge, 
failure  to  keep  records  of  staff  training,  failure  to  notify  that  a  premise  is  no  longer 
used for contained uses) and documentation management (e.g lack of complete, up-to 
date, accurate documentation, incomplete records of staff working in the premises); 

  waste management (inactivation method not validated); 

 

failure to notify activities involving the use of GMMs (Ireland). 

France  noted  difficulties  reported  by  applicants  concerning  the  risk  assessment  of  GMMs 
contained uses of classes 2 and 3 to file the notifications for the correct containment level. To 
overcome  these  difficulties,  the  competent  authority  and  the  independent  expert  committee 

10 Italy, Greece, Italy, Latvia, and Portugal.  
11 Spain and Austria and Spain. 
12 France, the Netherlands, Slovenia and Finland. 

6 

 
                                                 
 
jointly prepared a guidance document on the principles of risk assessment for contained use of 
GMOs (including GMMs).  

In  terms  of  enforcement,  Member  States  reported  on  action  taken.  When  inspections 
identified situations requiring corrective actions, different measures were adopted (inspection 
reports,  letters,  warnings,  fines,  etc.)  to  take  remedial  action  and  bring  the  use  back  into 
compliance within a set timeframe. If the non-compliance could result in an increased risk for 
human  or  animal  health  or  for  the  environment,  all  activities  involving  GMMs  were 
issues  (e.g.  regarding 
immediately  stopped  and 
documentation),  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. 

the  GMMs  destroyed.  For  minor 

Cyprus  noted  that  since  2018  there  has  been  only  one  research  institute  approved  for  the 
contained  use  of  GMMs  (only  working  with  class  1  and  class  2  uses),  and  highlighted  the 
need  for  identifying  and  raising  awareness  of  other  premises/installations  (institutes, 
universities,  laboratories,  etc.)  which  may  have  obligations  under  the  Directive.  For  this 
reason,  the  competent  authority  published  a  newsletter  and  sent  information  letters  to  all 
potential  operators  which  might  work  with  GMMs,  informing  them  about  the  regulatory 
requirements. The competent authority stressed the need to intensify this approach and carry 
out specialized inspections. 

Belgium  highlighted  potential  challenges  related  to  the  Do-It-Yourself  (DIY)(Bio)  practice, 
which  aims  at  giving  everyone  with  an  interest  in  biotechnology/bio(medical)  sciences  the 
opportunity  to  develop  research  projects  (open  source  science).  Challenges  arise  from  the 
difficulty to  ensure oversight  by professionals  or  competent  authorities  of such activities, in 
particular  where  individuals  design  and  conduct  experiments  with  GMOs  at  home  (“garage 
biology”),  without  necessarily  respecting  biosafety  regulations  and  standards.  The  Belgian 
Service  Biosafety  and  Biotechnology  (SBB)  is  currently  working  with  the  competent 
authorities  on  the  potential  challenges  associated  with  the  application  of  the  Directive  in 
relation to this practice. 

4.  Accidents 

No accidents (according to the definition of ‘accident’13 in Article 2(d) of the Directive) were 
reported. 

Some  Member  States14  reported  incidents  without  consequences  on  human  health  or  the 
environment.  Therefore,  these incidents  were not  communicated to  the Commission  and the 
other Member States. 

Those incidents involved classes 1 and 2 contained uses. The majority of incidents happened 
due to human error. 

Member  States  who  reported  incidents  indicated  that  they  have  a  system  in  place  to  handle 
such  situations  which  is  based  on  risk  analysis  to  establish  corrective  measures  and  avoid 
further  incidents  in  the  future.  Concerned  Member  States  involved  experts  and  provided 
recommendations  to  users and training.  As part of the follow-up, risk analyses were carried 

13 ‘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 
14 Belgium, Denmark, Germany, the Netherlands and Finland. 

7 

 
                                                 
 
out by the operators/users, incident reports were drawn up and action plans to eliminate any 
risk were sent to the competent authorities. 

All  the  entities  where  incidents  took  place  made  the  necessary  adjustments  to  improve  the 
procedural  aspects  to  avoid  similar  cases  in  the  future,  such  as  adapting  or  changing  their 
standard  operating  procedures,  amending  the  risk  assessment  and  providing  training  to  the 
staff. 

5.  Public information and consultation 

No changes in the provision of information to the public on contained uses of GMMs since 
the last reporting period have been reported by Member States. 

Germany  reported  on  adaptations  in  its  federal  legislation  as  regards  the  conduct  of  public 
consultations during COVID-19 pandemic. 

In  Hungary  questions  have  been  raised  on  the  handling  of  confidential  data.  A  consultation 
mechanism between  the  competent  authority  and  users  was  established in order to  facilitate 
the authorisation procedure and handle confidential data. 

Public consultations mainly concerned classes 3 and 4 contained uses. 

In  most  Member  States,  public  consultations  are  done  via  online  tools  and  comments  are 
rarely made by public. In Belgium (Flemish Region), the public is consulted in the framework 
of the request for environmental permit. There were approximately 30% of the cases of public 
consultations  in  which  observations  and  objections  were  taken  into  consideration  by  the 
competent authority.  

6.  Interpretation of the Directive 

Many Member States15 did not report any specific challenges regarding the interpretation of 
the Directive.  

However,  some  Member  States16  mentioned  difficulties  linked  to  the  definitions  in  the 
Directive,  particularly  in  the  context  of  new  genomic  techniques  and  synthetic  biology,  the 
correct classification of the contained uses and the legal status of certain products obtained by 
new genomic techniques. 

Finland  considered  that  the  definitions  in  the  Directive  are  outdated  and  have  been  a  major 
problem  particularly  concerning  new  genomic  techniques  and  in  the  current  research 
environment. According to Finland, this creates legal uncertainty as both the operators and the 
authorities have sometimes doubts on whether a notification is actually required or not. 

In  addition  to  this,  Finland  pointed  out  difficulties  in  classifying  uses  of  viruses  and  cell 
cultures, particularly in cases where their pathogenicity has been reduced   , and reported on 
the existence of different views about the legal status of micro-organisms when nucleic acids 
are transiently introduced in the host cell but these are not inherited by the progeny and when 
the  organism  resulting  from  the  genetic  modification  is  genetically  identical  to  a  wild-type 
organism.  In  that  regard,  it  asked  for  the  development  of  Commission  guidance  clarifying 
these questions. 

15 Denmark, Estonia, Greece, Cyprus, Latvia, Lithuania, Poland, Portugal, Slovakia and Slovenia. 
16 The Czech Republic, Germany, Luxembourg, the Netherlands and Finland. 

8 

 
                                                 
 
Finally,  in  view  of  the  frequently  changing  premises  of  individual  research  groups  and 
organisations  as  well  as  SMEs,  Finland  asked  for  a  reconsideration  of  the  notification 
requirements in Article 6 of the Directive, at least as regards class 1 uses, in order to lower the 
administrative burden. 

The Czech Republic raised questions on the legal status of certain products (e.g. whether cell 
lines, tissue samples or sub-cellular elements fall under the Directive).  

The Netherlands reported difficulties with  the interpretation  of the definition of GMOs, e.g.  
in relation to viral replicons17, and stressed that the general principles and specific measures 
required  in  Annex  IV  of  Directive  could  not  be  appropriately  applied  for  some  notified 
activities,  e.g.  in  relation  to  the  production  of  advanced  therapy  medicinal  products 
(ATMPs)18 and vaccines.   

Some  Member  States  (Czech  Republic,  Netherlands  and  Finland)  highlighted  that  the 
GMO/GMM  definitions  should  be  updated  in  light  of  the  application  of  new  molecular 
biology  techniques.  Finland  also  suggested  to  evaluate  the  pros  and  cons  of  a  technology-
based  regulation  versus  a  trait-based  regulation  when  dealing  with  rapidly  developing 
techniques.  The  Netherlands  saw  a  need  for  a  discussion  on  the  interpretation  of  the  GMO 
definition at the EU level. 

France highlighted difficulties applying the Directive as regards in vitro random mutagenesis 
following  the  decision  of  the  French  Council  of  State  of  7.2.202019.  France  also  asked 
whether the techniques and organisms that fall within the scope of Directive 2009/41/EC are 
to be considered identical to those falling under Directive 2001/18/EC. 

Germany  noted  that  several  competent  authorities  of  the  Federal  States  pointed  to  a lack  of 
clarity regarding the application to GMMs of the Court of Justice of the EU (CJEU) judgment 
in  Case  C-528/1620  concerning  organisms  obtained  by  new  techniques/methods  of 
mutagenesis.  It  reported  discussions  with  operators,  where  the  definition  of  GMO  was  no 
longer clear for newly developed techniques (such as CRISPR/Cas) and raised questions on 
the  classification  of  activities  for  the  production  of  organisms  with  a  low  risk,  created  in  a 
closed system, using the new genomic techniques.  

Bulgaria, Italy and Sweden noted the complexity in distinguishing between contained use and 
deliberate release as regards clinical trials with GMOs/GMMs, and Spain highlighted that the 
fact that Member States have different interpretations and approaches creates difficulties for 
the competent authorities, companies and users.  

Sweden  reported  on  ongoing  work  to  clarify  the  national  requirements  concerning  clinical 
trials  with  GMMs  as  regards  their  transportation,  storage  and  preparation  before  medicinal 
product are administered to patients (i.e., clinical trial subjects).   

17  A viral replicon is a genetic material originated from a viral genome and which can self-replicate (construct 
an identical copy of itself). 
18 ATMPs are medicines for human use that are based on genes, tissues or cells. 
19 https://www.conseil-etat.fr/decisions-de-justice/dernieres-decisions/conseil-d-etat-7-fevrier-2020-organismes-
obtenus-par-mutagenese 
20 Judgment of 25.7.2018, Case C-528/16, Confédération paysanne and Others (ECLI:EU:C:2018:583) 

9 

 
 
                                                 
 
Ireland suggested to align the requirements for class 1 uses with Directive 2000/54/EC on the 
protection of workers from  risks related to  exposure to  biological  agents at  work21, because 
class  1  uses  involve  usually  strains  with  a  long  history  of  safe  use,  which  present  no  or 
negligible  risk.  It  noted  that  Directive  2000/54/EC  does  not  require  the  notification  of 
activities involving risk group 1 biological agents but requires compliance with the principles 
of Good Occupational Safety and Hygiene. 

Norway  asked  which  regulatory  framework  to  apply  when  it  comes  to  uses  involving  GM 
animals  at  different  animal  developmental  stages,  as  national  requirements  on  GM-animals 
are  not  properly  adapted  to  this,  and  the  Directive’s  requirements  (including  on  cells  in 
culture) are often better suited.  

7.  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 national Member States reports.  

For  those  Member  States  that  have  extended  the  scope  of  their  national  legislation  to  the 
contained use of GM animals and GM plants22, information on the number of notifications for 
contained uses of GMOs other than GMMs submitted is also provided in the national Member 
States reports. 

There are no major changes in the number or the type of notifications received. 

The number of notifications varies yearly for some Member States. An overall tendency is a 
slowly decreasing number of notifications regarding plant research and an increasing number 
of research related to pharmaceutical/therapeutic applications (Spain and Finland). 

Finland noted that core facilities providing GMO services to other operators (research groups 
or  companies)  are  becoming  more  widespread.  The  number  of  notifications  from  the 
commercial sector has remained low in  comparison with  the basic research sector.  The vast 
majority  of  notifications  concern  biomedical  research  and  relate  to  research  activities  under 
class 2. 

However, notifications of class 3  uses have increased, some of them  (during the  year 2020) 
related  to  the  SARS-CoV-2  virus  (Spain  and  Germany).  Germany  reported  around  30%  of 
class  3  activities  concerning  research  on  SARS-CoV-2.  Slovenia  and  France  noted  that  the 
number of notifications almost doubled in the reporting period, particularly in class 2 uses due 
to the COVID-19 pandemic, since many research institutions started research on  the SARS-
CoV-2  virus.  France  highlighted  that  in  2020,  during  the  pandemic,  the  number  of 
notifications increased by 27.5% compared to the previous year. 

Norway  reported  an  increase  in  notifications  of  class  2  uses  of  GMMs,  alone  or  in 
combination  with  GM  animals,  and  noted  a  stable  number  of  notifications  from  large  scale 
production of GMOs, clinical trials with GMO medicines, GMOs used in education and from 
the use of GM animals and GM plants. 

21 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). 
22 All, except Estonia, Greece, Italy, Cyprus, Latvia, Luxembourg and Romania. 

10 

 
                                                 
 
Some Member States observed an increase in the overall number of notifications, in particular 
in 2021, and noted an increase in the number of GM lines in animal testing. 

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

Class of use 

Number 
of MS 

No notifications  1 

Greece 

Class 1 only 

Up to class 2 

3 

7 

Up to class 3 

12 

Bulgaria, Latvia, Romania 

Cyprus  (only  class  2),  Croatia,  Lithuania,  Norway,  Slovenia, 
Slovakia and Iceland  

Austria, Belgium, the Czech Republic, Denmark, Estonia, Spain, 
Ireland,  Italy,  Luxembourg,  the  Netherlands,  Portugal  and 
Finland 

Up to class 4 

4 

Germany, France, Sweden, Hungary  

The majority of the Member States that received notifications for GM plants or GM animals23 
did not encounter specific challenges related to those. 

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

All Member States, except Lithuania and Croatia, reported no changes in the  manufacturing 
and administration of investigational medicinal products (IMPs) for human and veterinary use 
(table 2). 

Lithuania amended the national legislation and procedures for authorisation of clinical trials 
under Regulation 536/201424. 

Croatia issued a guidance for clinical research. 

Table 2: Authorisation of IMPs under the Directive and total number of authorisations 

Human use 

Veterinary use 

Manufacturing 

Administration 

Manufacturing 

Administration 

AT 

BE 

Yes / 0 

Yes / 11 

Yes / 0 

Yes / 94 

Yes / N.D 

Yes / N.D 

Yes / 0 

Yes / 0 

23 Belgium, the Czech Republic, Denmark, Ireland, France, Croatia, Hungary, the Netherlands, Austria, Portugal, 
Slovenia and Slovakia. 
24  Regulation  (EU)  No  536/2014  of  the  European  Parliament  and  of  the  Council  of  16  April  2014  on  clinical 
trials on medicinal products for human use, and repealing Directive 2001/20/EC. 

11 

 
 
 
 
                                                 
 
BG 

CY 

CZ 

DE 

DK 

EE 

EL 

ES 

FI 

FR 

HR 

HU 

IE 

IT 

LT 

LU 

LV 

MT 

NL 

PL 

PT 

RO 

SE 

SI 

SK 

N.A 

N.A 

Yes / 11 

Yes / 6 

Yes / 5 

Yes / 2 

N.A 

Yes /58 

Yes / 72 

N.A 

N.A 

N.A 

Yes /N.D 

N.A 

Yes /2 

Yes / 0 

N.A 

N.A 

Yes / 0 

Yes / 0 

N.A 

Yes / 1 

Yes / N.D 

N.A 

N.A 

N.A 

N.A 

Yes / 0 

Yes / 15 

N.A 

No 

Yes/ 0 

Yes / N.D 

Yes/0 

N.A 

N.A 

Yes/ N.D 

Yes / 0 

N.A 

N.A 

N.A 

N.A 

Yes/ N.D 

N.A 

N.A 

N.A 

Yes / 0 

Yes / N.D 

Yes / N.D 

N.A 

N.A 

Yes/ 8 

Yes / 5 

Yes / 0 

Yes / 2 

N.A 

No 

Yes / 68 

Yes/3 

N.A 

N.A 

No 

N.A 

Yes /0 

Yes / 0 

N.A 

N.A 

N.A 

No report submitted 

N.A 

N.A 

N.A 

N.A 

N.A 

N.A 

N.A 

Yes /N.D 

N.A 

N.A 

Yes / 0 

N.A 

N.A 

 Yes /0 

No 

N.A 

No 

Yes / 0 

N.A 

N.A 

N.A 

N.A 

N.A 

N.A 

N.A 

N.A 

N.A 

N.A 

N.D: not determined 

N.A: Clinical trials with IMP containing GMOs are not regulated under the Directive.  

12 

 
France and Slovakia reported applying fast-track procedures to process applications related to 
the COVID-19 pandemic, in accordance with the derogation provided in Regulation (EU) No. 
2020/104325, which applied to the environmental risk assessment of IMP (prior environmental 
risk assessment for clinical trials not required as long as COVID-19 is considered a pandemic 
by the WHO) and the consent under the Directive. 

Spain  acknowledged  that  significant  progress  has  been  done  on  the  interplay  between  the 
GMO and the medicinal products legislation, and that it would be desirable to continue work 
to  harmonise  and  clarify  the  legal  framework  for  clinical  trials  with  GMOs/GMMs  at  EU 
level.  France  stressed  that,  since  the  implementation  of  the  common  application  forms  for 
IMPs,  the  environmental  risk  assessment  has  greatly  improved  as  only  relevant  information 
was required by the competent authorities. 

Italy reported difficulties by sponsors, authorisation holders and users to cooperate in order to 
prepare  the  notification  to  the  competent  authorities,  particularly  in  a  case  of  multicentre 
clinical  trials,  and  highlighted  that  a  better  cooperation  with  the  other  national  competent 
authorities would allow to get more data and to improve the monitoring system. Italy stressed 
the importance of having a harmonised approach among the competent authorities.  

Belgium  developed  a  practical  guidance  in  order  to  help  clinical  trial  sponsors  and 
investigators  of  IMPs  to  determine  the  procedural  requirements  to  be  followed  for  their 
clinical trial with GMO-medicinal products and noted that the Federal Agency for Medicines 
and  Health  Products  also  provided  a  preliminary  advice  on  which  legislative  procedures  on 
biosafety should be followed. 

A few Member States (Spain, France and Italy) called for a European consensus on regulatory 
aspects of clinical trials and early access to new medicinal products containing or consisting 
of GMOs. 

PART III: GENE DRIVE MODIFIED ORGANISMS 

Gene  drive26  modified  organisms  (GDOs)  are  not  covered  by  the  Directive  if  they  do  not 
involve the use of microorganisms as defined in the Directive. Nevertheless, Member States 
were invited to provide information, if any, on their experience with regulating the contained 
use of GDOs and how the national legislation, if any, is applied in this respect. 

Only  Germany  reported  a  change  in  national  legislation  since  the  last  reporting  period  and 
noted  that  the  provisions  on  GDOs  have  been  included  in  the  newly  amended  genetic 
engineering  safety  regulation  (‘Gentechnik-Sicherheitsverordnung’).  Activities  with  GDOs 
are initially assigned a safety level of class 3, which requires an approval (prior consent) by 
the  competent  authority  before  they  can  proceed  (Article  9(2)  Directive  2009/41/EC).  An 
advisory board is involved in a case-by-case assessment and the recommendation of specific 
safety  measures  are  issued  on  this  basis.  The  competent  authority  can  assign  another  safety 
level to the activities on the basis of a risk evaluation as well. Individual safety measures are 
specifically tailored to the organism in question. 

25 Regulation (EU) 2020/1043 of the European Parliament and of the Council of 15 July 2020 on the conduct of 
clinical  trials  with  and  supply  of  medicinal  products  for  human  use  containing  or  consisting  of  genetically 
modified organisms intended to treat or prevent coronavirus disease (COVID-19), OJ L 231, 17.7.2020, p. 12. 
26 For the purpose of this report, "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. 

13 

 
                                                 
 
Two Member States (Italy and the Netherlands) reported new notifications for GDOs received 
under their contained use legislation: 

  on Anopheles gambia for the development of GM mosquitoes for malaria control, 
and  Aedes  aegypti  mosquitoes  and  Drosophila  suzukii  genetically  modified  with 
reduced reproductive capacity of offspring (2 notifications of class 2 – Italy); 

  on nematode Caenorhabditis elegans to study the spread of a gene drive and the 
possibility  of  resistance  development  against  it  (one  notification  of  class  2  – 
Netherlands). 

These Member States shared their practical experience27 applying containment and protective 
measures for activities involving GDOs.  

Some  Member  States28  provided  their  views  on  risk  assessment  and  risk  management  of 
GDOs and noted that the risk classification system applied at national level to GDOs and the 
containment  measures  would  be  the  same  as  the  ones  the  Directive  provides  for  GMMs. 
However, the specific characteristics of the GDOs should be taken into account on a case-by-
case basis29. 

Belgium  noted  that  the  risk  assessment  and  risk  classification  principles  provided  by  the 
Directive for GMMs in contained use remain appropriate for activities with GDOs. However, 
Belgium  highlighted  that  in  the  processes  of  risk  assessment  and  risk  management,  specific 
characteristics of the GDO (the rapid spread of the GDO-carried modification through several 
generations  of  target  or  non-target  organisms)  should  be  considered.  Some  other  aspects 
would  also  merit  further  attention,  depending  on  the  particular  GDO  manipulated,  for 
example  if  it  is  an  arthropod.  In  this  context,  the  SBB  has  contributed  to  the  elaboration  of 
guidelines  to  help  users  and  competent  authorities  in  the  classification  and  management  of 
activities with GDOs30. 

Some Member States31 have adopted emergency plans for contained uses with GDOs. 

Bulgaria indicated that it would be appropriate to consider initially that any GDO will pose a 
high  risk  for  the  environment  and  to  apply  stringent  containment  measures.  Less  stringent 
containment measures could be set on a case-by-case basis if it is demonstrated that the risks 
are lower.  

Sweden noted that if a GMM was modified with a gene drive mechanism, it should be subject 
to contained use of at least class 2.  

Some  Member  States32  stressed  that  their  experience  with  GDOs  is  still  very  limited  and 
expertise is needed in this field. Those Member States highlighted that the rapid development 
of  the  technology  and  the  containment  adaptation  to  it,  as  well  as  uncertainties  on 
environmental  risk  assessment  are  important  elements  to  be  considered  for  activities  with 
GDOs. 

27 The detailed information is available in national reports. 
28  Belgium,  Bulgaria,  the  Czech  Republic,  Germany,  Ireland,  Spain,  Italy,  Luxembourg,  Lithuania,  the 
Netherlands, Finland and Sweden. 
29 the Czech Republic, Spain, Luxembourg and Finland 
30 CJB van der Vlugt, DD Brown, K Lehmann, A Leunda, N Willemarck (2018). 
31 Belgium, the Czech Republic and the Netherlands. 
32 Bulgaria, the Czech Republic, Ireland, Lithuania and Finland. 

14 

 
                                                 
 
Ireland  requested  guidelines  or  regulatory  information  specifically  addressing  biosafety  and 
gene drive use. 

CONCLUSIONS 

Member States reported their experience with  the Directive for the period 2019-2021 to  the 
Commission.  This  report  summarises  their  contributions  on  various  aspects  of  the 
implementation  of  the  Directive  and  their  experience  with  IMPs  and  GDOs.  Some 
clarifications from the Commission are also added in this section, to address Member States’ 
comments. 

In a few Member States national legislation was adapted in order to reflect the current state of 
science and technology development and the need to keep up to date the level of knowledge 
and expertise for the assessment of contained uses of GMOs/GMMs. 

In general, the national reports show that Member States cope well with the implementation 
of  the  Directive  and  ensure  that  all  measures  are  taken  to  avoid  adverse  effects  on  human 
health  and  the  environment  which  might  arise  from  the  contained  use  of  GMMs.  However, 
some Member States considered the GMO/GMM definitions do not reflect the current state of 
development  of science and technology  and a few Member States  considered  that there is  a 
lack of legal clarity as regards organisms obtained by new genomic techniques, following the 
Court of Justice of ruling in Case C-528/16 concerning  mutagenesis. 

In  this  regard,  the  Commission  recalls  that,  in  its  2015-2018  report33,  it  referred  to  the 
applicability of the interpretation made by the Court of Justice of the mutagenesis exemption 
set out in Directive 2001/18/EC (Article 3(1) of that Directive read in conjunction with point 
1 of Annex IB) and confirmed that it also applies to the exemption of mutagenesis techniques 
in point 1 of Part A of Annex II to Directive 2009/41/EC. Some clarifications on the scope of 
the  Directive  were  also  given  in  the  Commission  Staff  Working  Document  “Study  on  the 
status of new genomic techniques under Union law and in light of the Court of Justice ruling 
in  Case  C-528/16”  (“Commission  study  on  new  genomic  techniques”)  published  in  April 
202134.  

Some  Member  States  reported  difficulties  in  the  notification  and  approval  process.  Those 
were  related  to  the  time  limits  for  processing  notifications  and  following  the  administrative 
procedures as well as to requests for additional information needed for risk assessment due to 
the complexity of notifications.  

In  order  to  reduce  administrative  burden,  one  Member  State  suggested  aligning  the 
requirements for contained use of class 1 with the requirements in Directive 2000/54/EC on 
the protection of workers from risks related to exposure to biological agents at work. 

It should be noted that both Directives share the common goal to protect human health against 
risks arising or likely to arise from exposure to biological agents. However, in addition to this, 
Directive  2009/41/EC  has  the  objective  to  protect  the  environment  and  lays  down  the 
measures to this effect.  

The  national  reports  highlighted  once  again  the  complexity  of  completing  notification  and 
authorisation procedures under different regulatory frameworks for IMPs i.e. under Directive 

33 COM(2021) 266 final 
34 SWD(2021) 92 final 

15 

 
                                                 
 
2009/41/EC  and  Regulation  (EU)  No  536/2014  respectively,  differences  in  Member  States’ 
approaches as regards the environmental risk assessment of clinical trials with IMPs and the 
need to  continue working to harmonise this field. This  issue was  particularly  highlighted in 
the context of the COVID-19 pandemic and access to medicinal products that were urgently 
needed to overcome/prevent emerging public health issues.  

The  Commission’s  Communication  on  a  Pharmaceutical  Strategy  for  Europe35  recognized 
that the regulatory requirements for the authorisation of medicines for human use that contain 
or consist of GMOs should be fit for purpose when it comes to addressing the specificities of 
medicines  and  the  conduct  of  clinical  trials  with  those  products  in  the  EU.  It  furthermore 
indicated  that  solutions  would  be  explored  during  the  evaluation  of  the  pharmaceutical 
legislation  considering  the  mechanisms  for  the  continuous  and  timely  adaptation  of  its 
technical requirements in light of emerging science and technologies with a view to enhance 
effectiveness  and  protect  human  health  while  minimising  harmful  impacts  on  the 
environment. 

In terms of enforcement, no serious cases of non-compliance have been reported as  regards 
safety for human health and the environment. 

The COVID-19 pandemic has forced enforcement authorities to swiftly adjust their practices, 
dealing  with  specific  challenges  and  limitations  on  the  possibility  to  conduct  on-site 
inspections, and requiring changes in work patterns imposed by lockdowns, while at the same 
time ensuring that biotechnology research is conducted under safety conditions. 

In general, competent authorities responded to the COVID-19 pandemic using different tools, 
and  a  number  of  measures  were  introduced  following  a  risk-based  approach  that  prioritised 
inspections  and  enforcement  in  areas  where  critical  risks  were  identified,  and  temporarily 
suspending inspections of low-risk contained-use activities. The use of digital tools was also 
highlighted  as  a  way  to  increase  knowledge  and  skills  for  the  prevention  of  risks  and 
protection  of  health  and  the  environment  in  the  case  of  contained  use  of  GMMs  between 
research institutions, in order to share knowledge and gather new evidence. 

As  regards  GDOs,  the  national  reports  show  that  experience  in  this  field  is  still  limited. 
Reporting Member States indicated that there would be  no particular challenges in applying 
the same measures for GDOs as the ones the Directive provides for GMMs, and that the risk 
assessment  and  risk  classification  principles  provided  in  the  Directive  would  be  appropriate 
for  activities  with  GDOs,  while  considering  their  specific  characteristics  on  a  case-by-case 
basis. 

Some Member States have requested  guidance addressing  biosafety issues in  relation  to  the 
contained use of GMMs, particularly in the context of biotechnology developments and new 
genomic techniques. 

The  Commission  study  on  new  genomic  techniques  published  in  2021  concluded  that  the 
necessary scientific knowledge on the application of these techniques in GMMs is still limited 
or lacking, especially on safety aspects. The report, explained that, as regards the use of new 
genomic techniques in microorganisms, the Commission intended to continue to build up the 
required  scientific  knowledge,  in  view  of  possible  further  policy  actions36.  To  this  end,  the 

35 COM(2020) 761 final 
36 Based on the findings of the study, the Commission is working on an initiative to propose a legal framework 
for  plants  obtained  by  targeted  mutagenesis  and  cisgenesis  and  for  their  food  and  feed  products: 

16 

 
                                                 
 
European  Food  Safety  Authority  has  been  mandated  to  gather  information  and  provide  an 
opinion on new developments in biotechnology applied to microorganisms, in order to get an 
up-to-date and deeper understanding of the use of the technologies in this area and of possible 
risks associated to them37. In addition, the European Network of GMO Laboratories, assisted 
by the European Union Reference Laboratory on GM food and Feed, is developing a report 
on the detection of GMMs, including those obtained by new mutagenesis techniques38. 

The Commission organises regular meetings of the national competent authorities responsible 
for  the  Directive,  where  it  will  continue  to  discuss  with  these  authorities  relevant  issues 
concerning the implementation of the Directive. 

https://ec.europa.eu/info/law/better-regulation/have-your-say/initiatives/13119-Legislation-for-plants-produced-
by-certain-new-genomic-techniques_en 
37 https://open.efsa.europa.eu/questions/EFSA-Q-2022-00508   
38 https://gmo-crl.jrc.ec.europa.eu/ENGL/docs/MandateENGL_WG_GMM.pdf  

17