Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL amending Regulation (EU) No 536/2014 as regards a derogation from certain obligations concerning investigational medicinal products made available in the United Kingdom with respect to Northern Ireland as well as in Cyprus, Ireland and Malta
Date: 2021-12-17
Institutions: Directorate-General for Health and Food Safety, European Commission
Subjects: Cyprus, Ireland, Malta, Northern Ireland, United Kingdom, clinical trial, import, import licence, market approval, medicinal product, security of supply

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   EUROPEAN COMMISSION  Brussels, 17.12.2021  COM(2021) 998 final 2021/0432 (COD)  Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL amending Regulation (EU) No 536/2014 as regards a derogation from certain obligations concerning investigational medicinal products made available in the United Kingdom with respect to Northern Ireland as well as in Cyprus, Ireland and Malta (Text with EEA relevance)  
 
EXPLANATORY MEMORANDUM 

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CONTEXT OF THE PROPOSAL 

Reasons for and objectives of the proposal 

Pursuant  to  the  Protocol  on  Ireland/Northern  Ireland  (“the  Protocol”)  of  the 
Agreement on the withdrawal of the United Kingdom of Great Britain and Northern 
Ireland from the European Union and the European Atomic Energy Community1 (the 
‘Withdrawal  Agreement’),  the  importation  of  investigational  medicinal  products 
from third countries into the Union or Northern Ireland is subject to the possession of 
a  manufacturing  and  import  authorisation.  These  shall  be  in  compliance  with  the 
obligations of the EU acquis for clinical trials. 

During these last years, the United Kingdom in respect of Northern Ireland as well as 
the  small  markets  of  the  European  Union  (i.e.  Malta,  Ireland  and  Cyprus)  that  are 
dependent  on  supply  of  medicinal  products  from  the  United  Kingdom,  have  raised 
issues with respect to the ability of economic operators to comply with all provisions 
of the acquis for medicines after the end of the transition period provided for in 
the  Withdrawal  Agreement,  including  medicines  used  in  clinical  trials,  having 
regard in particular to the importation requirements.  
The Commission Notice of 25 January 20212 provides for a grace period of one year 
(until  end-December  2021),  including  for  the  importation  requirements  for 
investigational  medicines,  to  ensure  undisrupted  supply  of  medicines  to  Northern 
Ireland, Cyprus, Ireland and Malta.  

Despite  the  transition  period,  it  still  proves  very  difficult  for  certain  operators 
currently based in parts of the United Kingdom other than Northern Ireland to adapt 
as  required  by  the  Protocol.  The  main  reasons  are  the  too  high  adjustment  costs 
relative  to  the  small  size  of  the  Northern  Irish  market  and  the  complex  logistics 
involved,  for  which  no  viable  alternative  logistical  hubs  in  Northern  Ireland  have 
been identified.  

For the markets of Cyprus, Malta and Ireland, the same issues arose, and in addition, 
difficulties  were  seen  with  to  ensure  that  clinical  trial  participants  have  access  to 
certain medicinal products due to supply chains reliance on other parts of the United 
Kingdom than Northern Ireland.  

Disruption in supply of investigational medicinal products would pose potential risk 
to the safety and well-being of participants in ongoing clinical trials as well as hinder 
the setting up of new clinical trials in these Member States and in Northern Ireland.  

The  objectives  of  this  proposal  are  to  address  the  issues  related  to  investigational 
medicinal products, to prevent an adverse impact on their supply and, as a result, on 
the  execution  of  clinical  trials  authorised  under  Regulation  (EU)  536/20143  in 
Northern Ireland, Cyprus, Ireland and Malta. 

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OJ L 29, 31.1.2020, p. 7. 
Commission  Notice  of  25  January  2021  on  the  application  of  the  Union’s  pharmaceutical  acquis  in 
markets historically dependent on medicines supply from or through Great Britain after the end of the 
transition period, (OJ C 27, 25.1.2021, p. 11).  
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  (OJ  L  158, 
27.5.2014, p. 1).  

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This  proposal  allows exceptionally that  the manufacturing and import authorisation 
is not required for investigational medicinal products imported into Cyprus, Ireland, 
Malta and Northern  Ireland  from  parts of the  United Kingdom  other than Northern 
Ireland, provided that certain conditions are fulfilled. For Cyprus, Ireland and Malta, 
this  derogation  is  of  a  temporary  nature  as  it  is  expected  that  these  markets  will 
gradually be supplied through Member States. A transition period of 3 years seems 
sufficient.  

Although Regulation (EU) 536/2014 entered into force in 2014, its applicability was 
made dependent on the full functionality of the European Portal  and Database. The 
Commission published the notice of full functionality on 31 July 2021, triggering a 
6-month period before applicability on 31 January 2022.4 As a transitional measure, 
during the first year (until 31 January 2023), sponsors can chose to submit a clinical 
trial  application  in  line  with  the  rules  of  Regulation  (EU)  536/2014  or  through  the 
rules  of Directive 2001/20/EC5.  Trials  authorised under  that  Directive can continue 
until 31 January 2025.  

Therefore, this proposal should be read in conjunction with the conceptually identical 
changes to Directive 2001/20 proposed in COM(2021)997 of 17 December 2021 as 
both legal acts can apply to different clinical trials in the EU until 31 January 2025. 
For  this  reason,  this  separate  proposal  was  given  an  exemption  from  an  additional 
fiche for the agenda planning. Considering the urgency needed to address the issues, 
the roadmap for this initiative will not be provided. 

• 

Consistency with existing policy provisions in the policy area 

A  comprehensive  Union  medicinal  products  legislative  framework  was  established, 
in particular Directive 2001/83/EC6, Directive 2001/20/EC and Regulation (EU) No 
536/2014, which are of relevance for this initiative that will complement and amend 
them. 

This proposal is consistent with the objective to protect participants of clinical trials 
and public health in the small markets of the Union and in Northern Ireland. 

• 

Consistency with other Union policies 

This proposal does not affect other Union policies, except for the health and internal 
market rules. As a consequence, the assessment of the consistency with other Union 
policies is not considered necessary.  

2. 

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LEGAL BASIS, SUBSIDIARITY AND PROPORTIONALITY 

Legal basis 

As  this  proposal  amends  Regulation  (EU)  No  536/2014,  the  same  legal  basis   
Articles 114 and 168(4)(c) TFEU  are considered the appropriate legal basis for this 
proposal as well. 

Commission  Notice  of  25  January  2021  on  the  application  of  the  Union’s  pharmaceutical  acquis  in 
markets historically dependent on medicines supply from or through Great Britain after the end of the 
transition period, (OJ C 27, 25.1.2021, p. 11). 
Directive  2001/20/EC  of  the  European  Parliament  and  of  the  Council  of  4  April  2001  on  the 
approximation of the laws, regulations and administrative provisions of the Member States relating to 
the implementation of good clinical practice in the conduct of clinical trials on medicinal products for 
human use (OJ L 121, 1.5.2001, p. 34). 
Directive  2001/83/EC  of  the  European  Parliament  and  of  the  Council  of  6  November  2001  on  the 
Community code relating to medicinal products for human use (OJ L 311, 28.11.2001, p. 67). 

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• 

Subsidiarity (for non-exclusive competence)  

This  proposal  provides  exemptions  from  the  provisions  of  the  EU  pharmaceutical 
legislation and can only be achieved by an amendment of the basic act at EU level.  

This  proposal  aims  to  provide  derogations  for  medicinal  products  distributed  to 
Northern  Ireland,  Cyprus,  Ireland  and  Malta  that  are  used  as  investigational 
medicinal products in clinical trials in those countries. 

• 

Proportionality 

The  proposal  covers  the  exemption  from  the  importation  requirements  for 
investigational medicinal products to ensure their continued supply and avoid delays 
or  interruptions  to  the  setting  up  and  conduct  of  clinical  trials  in  the  Union  and  in 
Northern Ireland. 

The proposal is restricted to investigational medicines made exclusively available in 
Northern Ireland and the small markets of those EU Member States  Cyprus, Malta 
and Ireland  that are dependent on the UK market. 

• 

Choice of the instrument 

As the initiative amends Regulation (EU) No 536/2014, a proposal for a Regulation 
of the European Parliament and Council is considered the appropriate instrument. 

3. 

• 

• 

RESULTS 
CONSULTATIONS AND IMPACT ASSESSMENTS 

EX-POST 

EVALUATIONS, 

OF 

STAKEHOLDER 

Ex-post evaluations/fitness checks of existing legislation 

Not applicable 

Stakeholder consultations 

This initiative is proposed following bilateral discussion with the concerned national 
authorities and industry associations, who have expressed strong concerns due to the 
risk  of  interruptions  of  ongoing  or  future  clinical  trials  due  to  the  requirements  for 
importation of investigational medicinal products. 

Considering  that  targeted  consultations  with  the  Member  States  concerned  and  the 
stakeholders took place, another open public consultation will not be carried out. 

• 

Impact assessment 

The  proposal  is  exempted  from  the  impact  assessment  due  to  the  urgency  of  the 
situation,  to  ensure  public  health  through  the  continued  supply  of  investigation 
medicinal products for clinical trials in Northern Ireland and the small markets of the 
EU Member States that are dependent on the United Kingdom for their supplies. 

Regulatory fitness and simplification 

By  waiving  certain  regulatory  requirements  for  the  importation  of  investigational 
medicinal  products,  provided  certain  conditions  are  fulfilled,  the  proposal  reduces 
compliance costs in particular as regards SMEs.  

Fundamental rights 

The  proposed  Regulation  contributes  to  achieving  a  high  level  of  human  health 
protection as set out in Article 35 of the EU Charter of Fundamental Rights.  

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4. 

BUDGETARY IMPLICATIONS 

No budgetary implications are foreseen.  

5. 

• 

OTHER ELEMENTS 

Implementation plans and monitoring, evaluation and reporting arrangements 

The initiative applies to the United Kingdom in respect of Northern Ireland that must 
implement it and notify to the Commission the implementation planning associated 
with  this  initiative.  The  Member  States  concerned  as  well  must  take  the  necessary 
measures  to  implement  the  initiative.  The  Commission  will  further  monitor  its 
implementation.  

• 

Detailed explanation of the specific provisions of the proposal 

Not applicable for this proposal.  

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2021/0432 (COD) 

Proposal for a 

REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL 

amending Regulation (EU) No 536/2014 as regards a derogation from certain obligations 
concerning investigational medicinal products made available in the United Kingdom 
with respect to Northern Ireland as well as in Cyprus, Ireland and Malta 

(Text with EEA relevance) 

THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION, 

Having  regard  to  the  Treaty  on  the  Functioning  of  the  European  Union,  and  in  particular 
Articles 114 and 168(4), point (c), thereof, 

Having regard to the proposal from the European Commission, 

After transmission of the draft legislative act to the national parliaments, 
Having regard to the opinion of the European Economic and Social Committee1,  
Having regard to the opinion of the Committee of the Regions2,  

Acting in accordance with the ordinary legislative procedure, 

Whereas: 

(1) 

The  Agreement  on  the  withdrawal  of  the  United  Kingdom  of  Great  Britain  and 
Northern  Ireland  from  the  European  Union  and  the  European  Atomic  Energy 
Community3 (the ‘Withdrawal Agreement’) was concluded on behalf of the Union by 
Council  Decision  (EU)  2020/135 4 and  entered  into  force  on  1  February  2020.  The 
transition period referred to in Article 126 of the Withdrawal Agreement, during which 
Union  law  continued  to  apply  to  and  in  the  United  Kingdom  in  accordance  with 
Article  127  of  the  Withdrawal  Agreement  (the  ‘transition  period’),  ended  on  31 
December 2020. On 25 January 2021, the Commission issued a Notice5 (‘the Notice’) 
on  the  application  of  the  Union’s  pharmaceutical  acquis  in  markets  historically 
dependent  on  medicines  supply  from  or  through  Great  Britain  (i.e.  Cyprus,  Ireland, 
Malta and Northern Ireland) after the end of the transition period. This Notice includes 
explanations of how the Commission would apply the Union’s pharmaceutical acquis 
in  those  markets  with  regard  to  investigational  medicinal  products.  The  Notice  is  to 
cease to be applied on 31 December 2021.  

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OJ C , , p. . 
OJ C , , p. . 
OJ L 29, 31.1.2020, p. 7. 
Council  Decision  (EU)  2020/135  of  30  January  2020  on  the  conclusion  of  the  Agreement  on  the 
withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and 
the European Atomic Energy Community (OJ L 29, 31.1.2020, p. 1). 
Commission  Notice  –  Application  of  the  Union’s  pharmaceutical  acquis  in  markets  historically 
dependent  on  medicines  supply  from  or  through  Great  Britain  after  the  end  of  the  transition  period 
(2021/C 27/08)(OJ C 27, 25.1.2021, p. 11). 

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(2) 

(3) 

(4) 

(5) 

(6) 

(7) 

In accordance with the Protocol on Ireland/Northern Ireland, which forms an integral 
part of the Withdrawal Agreement, investigational medicinal products used in clinical 
trials in Northern Ireland are to comply with Union law. 
Regulation  (EU)  No  536/2014  of  the  European  Parliament  and  of  the  Council6  lays 
down  the  rules  for  investigational  medicinal  products  intended  to  be  used  in  clinical 
trials in the Union. That Regulation applies from 31 January 2022. 

In accordance with Article 61(1) of Regulation (EU) No 536/2014, read in conjunction 
with the Protocol on Ireland/Northern Ireland, the import of investigational medicinal 
products  from  third  countries  into  the  Union  or  Northern  Ireland  is  subject  to  the 
holding  of  a  manufacturing  and  import  authorisation.  Cyprus,  Ireland,  Malta  and 
Northern  Ireland  have  historically  relied  on  supply  of  medicinal  products,  including 
investigational medicinal products, from or through parts of the United Kingdom other 
than Northern Ireland, and the supply chains for these markets have not yet been fully 
adapted to comply with Union law In order to ensure that clinical trial participants in 
Cyprus,  Ireland,  Malta  and  Northern  Ireland  continue  to  have  access  to  new, 
innovative  or  improved  treatments,  it  is  necessary  to  amend  Regulation  (EU)  No 
536/2014  to  provide  for  a  derogation  from  the  requirement  of  the  holding  of  a 
manufacturing  and  import  authorisation  for  investigational  medicinal  products 
imported  into  those  markets  from  parts  of  the  United  Kingdom  other  than  Northern 
Ireland. However, both in order to ensure the quality of those investigational medicinal 
products  and  to  avoid  compromising  the  integrity  of  the  internal  market,  certain 
conditions should be laid down.  

Regulation (EU) No 536/2014 should therefore be amended accordingly. 

In light of the requirement of uniform application of Union law in the Member States, 
the  derogations  applicable  in  Cyprus,  Ireland  and  Malta  should  be  of  a  temporary 
nature only.  

In order to ensure legal continuity for operators active in this sector and to guarantee 
the  continuous  access  of  participants  in  clinical  trials    in  Cyprus,  Malta,  Ireland  and 
Northern Ireland to investigational medicinal products from the date of application of 
Regulation (EU) No 536/2014, this Regulation should enter into force as a matter of 
urgency  and  apply  retroactively  from  the  date  at  which  Regulation  (EU)  536/2014 
becomes applicable,  

HAVE ADOPTED THIS REGULATION: 

Article 1 

In Article 61(1) of Regulation 536/2014, the following subparagraph is added: 

“However,  the  import  of  investigational  medicinal  products  from  other  parts  of  the  United 
Kingdom into Northern Ireland and, until 31 December 2024, into Cyprus, Ireland and Malta 
shall not be subject to the holding of a manufacturing and import authorisation, provided that 
the following conditions are fulfilled:  

(a) 

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the investigational medicinal products have undergone certification of batch release 
either in the Union or in parts of the United Kingdom other than Northern Ireland to 
verify compliance with the requirements set out in Article 63(1);  

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  (OJ  L  158, 
27.5.2014, p. 1). 

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(b) 

the  investigational  medicinal  products    are  only  made  available  to  clinical  trial 
participants  in  the  Member  State  into  which  the  investigational  medicinal  products  
are imported or, if imported into Northern Ireland, are only made available to clinical 
trial participants in Northern Ireland.” 

Article 2 

This  Regulation  shall  enter  into  force  on  the  day  following  that  of  its  publication  in  the 
Official Journal of the European Union. 

It shall apply from 31 January 2022. 

This Regulation shall be binding in its entirety and directly applicable in all Member States. 

Done at Brussels, 

For the European Parliament 
The President 

For the Council 
The President 

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