Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL amending Regulation (EC) No 726/2004 as regards pharmacovigilance
Date: 2012-02-10
Institutions: European Commission
Subjects: European Medicines Agency, disclosure of information, drug surveillance, market approval, marketing standard, medicinal product

EUROPEAN COMMISSION 

Brussels, 10.2.2012  
COM(2012) 51 final 

2012/0023 (COD) 

Proposal for a 

REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL 

amending Regulation (EC) No 726/2004 as regards pharmacovigilance 

(Text with EEA relevance) 

 
 
 
 
EXPLANATORY MEMORANDUM 

The Commission presents a proposal for a Regulation of the European Parliament and of the 
Council  amending,  as  regards  pharmamacovigilance,  Regulation  (EC)  No  726/2004.  It  is 
complemented by parallel changes to Directive 2001/83/EC. 

1. 

CONTEXT OF THE PROPOSAL 

On 15 December 2010, the European Parliament and the Council adopted Directive 
2010/84/EU  and  Regulation  (EU)  No  1235/2010  ("2010  pharmacovigilance 
legislation")  amending  respectively,  as  regards  pharmacovigilance,  Directive 
2001/83/EC  and  Regulation  (EC)  No  726/2004.  The  new  legislation  shall  apply  in 
July 2012. 

The  adopted  measures  have  substantially  strengthened  the  legal  framework  for  the 
surveillance of medicinal products, with provisions to reinforce the coordinating role 
of the Agency, the possibilities for signal detection, and the operation of coordinated 
procedures at European level to respond to safety concerns.  

However, recent pharmacovigilance events in the European Union, in particular the 
so-called  “Mediator  case”,  have  shown  the  need  for  a  further  improvement  of  the 
pharmacovigilance system. 

Following  an  analysis  of 
the  2010 
the  Mediator  case 
pharmacovigilance  legislation  ("Stress  test"),  the  Commission  has  detected  certain 
weaknesses in the pharmacovigilance system which should be addressed. 

light  of 

the 

in 

In  particular,  Directive  2001/83/EC  provides  for  an  automatic  assessment  at  Union 
level  when  specific  serious  safety  issues  have  been  identified  with  regard  to 
nationally authorised products. In the 2010 pharmacovigilance legislation, changes to 
the Commission's proposal during co-decision have led to the automatism being lost, 
as the initiation of the procedure is linked to an appreciation by the Member State or 
the Commission as to whether an urgent action is considered necessary. Thus, when 
a Member State considers suspending, revoking or refusing renewal of a marketing 
authorisation, but does not consider that urgent action is needed, no evaluation of the 
safety concern will be conducted at Union level. 

Moreover, marketing authorisation holders are not required to declare the reasons for 
the withdrawal of a marketing authorisation or product. Therefore, it cannot be ruled 
out  that  voluntary  withdrawal  of  a  marketing  authorisation  or  product  by  the 
marketing authorisation holder could lead to safety issues being missed, in particular 
if the company is not transparent about possible safety concerns. 

Finally, the public list of medicinal product subject to additional monitoring provided 
for  in  Article  23  of  Regulation  (EC)  No  726/2004  will  include  certain  medicinal 
products  subject  to  post-authorisation  safety  conditions.  Those  products  will  be 
included  in  the  list,  following  consultation  with  the  Pharmacovigilance  Risk 
Assessment  Committee,  only  if  the  Commission  or  a  Member  States'  competent 
authorities make a request. Therefore, competent authorities will have to decide on a 

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case-by-case  basis  whether  to  make  public  the  fact  that  products  are  subject  to 
strengthened surveillance. 

2. 

OBJECTIVE OF THE COMMISSION'S PROPOSALS 

The  general  policy  objectives  of  the  proposals  to  amend  Directive  2001/83/EC  and 
Regulation  (EC)  No  726/2004  are  in  line  with  the  overall  objectives  of  the  EU 
pharmaceutical legislation. These are intended to ensure the proper functioning of the 
internal market for medicinal products for human use and to better protect health of 
EU  citizens.  Following  this  line,  the  proposals  aim  specifically  to  address 
weaknesses  identified  in  the  EU  pharmacovigilance  system  and  provide  for  more 
transparency  and  efficiency  of  the  system  in  cases  where  safety  concerns  are 
identified. 

3. 

BUDGETARY IMPLICATION  

The proposals have no implication for the budget of the Union. 

The  proposals  only  make  minor  changes  to  the  system  set  forth  by  the  2010 
pharmacovigilance 
require  additional  human  or 
administrative resources for the functioning of the pharmacovigilance system. 

legislation.  They  do  not 

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2012/0023 (COD) 

Proposal for a 

REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL 

amending Regulation (EC) No 726/2004 as regards pharmacovigilance 

(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 
Article 114 and Article 168(4)(c) thereof, 

Having regard to the proposal from the European Commission1, 

Having regard to the opinion of the European Economic and Social Committee2,  

Having regard to the opinion of the Committee of the Regions3, 

Acting in accordance with the ordinary legislative procedure, 

Whereas: 

(1) 

(2) 

In order to ensure transparency on the surveillance of authorised medicinal products, 
the  list  of  medicinal  products  subject  to  additional  monitoring  established  by 
Regulation  (EC)  No  726/2004  of  the  European  Parliament  and  of  the  Council  of 
31 March  2004  laying  down  Community  procedures  for  the  authorisation  and 
supervision  of  medicinal  products  for  human  and  veterinary  use  and  establishing  a 
European Medicines Agency4, as amended by Regulation (EU) No 1235/20105, should 
systematically include medicinal products that are subject to post-authorisation safety 
conditions. 

In addition, voluntary action by the marketing authorisation holder should not lead to a 
situation  where  concerns  related  to  the  risks  or  benefits  of  a  medicinal  product 
authorised  in  the  Union  are  not  properly  addressed  in  all  Member  States.  Therefore, 
provisions  should  be  made  for  the  marketing  authorisation  holder  to  inform  the 
Agency of the reasons for the withdrawal of a medicinal product, for interrupting the 
placing  on  the  market  of  a  medicinal  product,  for  requests  for  revoking  a  marketing 
authorisation, or for not renewing a marketing authorisation. 

1 
2 
3 
4 
5 

OJ C , , p. . 
OJ C , , p. . 
OJ C , , p. . 
OJ L 136, 30.4.2004, p. 1. 
OJ L 348, 31.12.2010, p. 1. 

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(3) 

Regulation (EC) No 726/2004 should therefore be amended accordingly. 

(4) 

Since  the  objective  of  this  Regulation,  namely  to  provide  for  specific  rules  on 
pharmacovigilance  and  improve  the  safety  of  medicinal  products  for  human  use 
authorised pursuant to Regulation (EC) No 726/2004 cannot be sufficiently achieved 
by  Member  States  and  can  be  better  achieved  at  Union  level,  the  Union  may  adopt 
measures, in accordance with the principle of subsidiarity as set out in Article 5 of the 
Treaty. In accordance with the principle of proportionality, as set out in that Article, 
this  Regulation  does  not  go  beyond  what  is  necessary  in  order  to  achieve  this 
objective, 

HAVE ADOPTED THIS REGULATION: 

Regulation (EC) No 726/2004 is amended as follows: 

Article 1 

(1) 

In Article 13(4), the second subparagraph is replaced by the following: 

"The  holder  shall  also  notify  the  Agency  if  the  product  ceases  to  be  placed  on  the 
market  of  the  Member  State,  either  temporarily  or  permanently.  Such  notification 
shall, otherwise than in exceptional circumstances, be made no less than two months 
before the interruption in the placing on the market of the product. The holder shall 
inform the Agency of the reasons for such action in accordance with Article 14b." 

(2) 

The following Article 14b is inserted: 

"Article 14b 

The  marketing  authorization  holder  shall  notify  the  Agency  of  any  action  taken  by 
him  to  suspend  the  marketing  of  a  medicinal  product,  to  withdraw  a  medicinal 
product  from  the  market,  to  request  the  withdrawal  of  a  marketing  authorisation  or 
not to apply for the renewal of a marketing authorisation, together with the reasons 
for such action. The marketing authorisation holder shall in particular declare if such 
action  is  linked  to  any  of  the  grounds  set  out  in  Articles  116  and  117  of  Directive 
2001/83/EC. 

In such case, the Agency shall ensure that this information is brought to the attention 
of the Member States."  

(3) 

Article 20(8) is replaced by the following: 

the  procedure  results  from 

"8.  Where 
to 
pharmacovigilance, the opinion of the Agency in accordance with paragraph 2 of this 
Article shall be adopted by the Committee for Medicinal Products for Human Use on 
the  basis  of  a  recommendation  from  the  Pharmacovigilance  Risk  Assessment 
Committee and Article 107j(2) of Directive 2001/83/EC shall apply." 

the  evaluation  of  data  relating 

(4) 

Article 23 is replaced by the following: 

"Article 23 

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1. The Agency shall, in collaboration with the Member States, set up, maintain and 
make public a list of medicinal products that are subject to additional monitoring. 

That list shall include the names and active substances of: 

(a)  medicinal  products  authorised  in  the Union  that  contain  a  new  active  substance 
which, on 1 January 2011, was not contained in any medicinal product authorised in 
the Union; 

(b)  any  biological  medicinal  product  not  covered  by  point  (a)  that  was  authorised 
after 1 January 2011; 

(c)  medicinal  products  that  are  authorised  pursuant  to  this  Regulation  subject  to 
conditions referred to in points (c), (ca), (cb) and (cc) of Article 9(4), or in Article 
10a, Article 14(7) and (8) and in Article 21(2); 

(d) medicinal products that are authorised pursuant to Directive 2001/83/EC, subject 
to the conditions referred to in Articles 21a, 22, 22a and 104a of that Directive. 

2. The list referred to in paragraph 1 shall include an electronic link to the product 
information and to the summary of the risk management plan. 

3.  In  the  cases  referred  to  in  points  (a)  and  (b)  of  paragraph  1  of  this  Article,  the 
Agency  shall  remove  a  medicinal  product  from  the  list  five  years  after  the  Union 
reference date referred to in Article 107c(5) of Directive 2001/83/EC. 

In the cases referred to in points (c) and (d) of paragraph 1, the Agency shall remove 
a medicinal product from the list once the conditions have been fulfilled. 

4.  For  medicinal  products  included  in  that  list,  the  summary  of  product 
characteristics  and  the  package  leaflet  shall  include  the  statement  “This  medicinal 
product  is  subject  to  additional  monitoring”.  That  statement  shall  be  preceded  by  a 
black  symbol  which  shall  be  selected  by 
the  Commission  following  a 
recommendation  of  the  Pharmacovigilance  Risk  Assessment  Committee  by  2 
January  2012,  and  shall  be  followed  by  an  appropriate  standardised  explanatory 
sentence." 

Article 2 

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

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

Done at Brussels, 10.2.2012 

For the European Parliament 
The President 

For the Council 
The President 

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