Proposal for a DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL amending Directive 2001/83/EC 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) 52 final 

2012/0025 (COD) 

Proposal for a 

DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL 

amending Directive 2001/83/EC as regards pharmacovigilance 

(Text with EEA relevance) 

 
 
 
 
EXPLANATORY MEMORANDUM 

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

regards  pharmamacovigilance,  Directive  2001/83/EC. 

It 

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  that  reinforce  the  coordinating 
role of the European Medicines 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. 

EXPLANATORY  DOCUMENTS  ACCOMPANYING  THE  NOTIFICATION 
OF TRANSPOSITION MEASURES AND BUDGETARY IMPLICATION  

As  the  proposed  Directive  aims  to  amend  only  a  very  limited  number  of  legal 
obligations  of  Directive  2001/83/EC,  correlation  tables  or  other  explanatory 
documents are not required to accompany the notification of transposition measures 
by the Member States.  

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

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

legislation.  They  do  not 

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2012/0025 (COD) 

Proposal for a 

DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL 

amending Directive 2001/83/EC 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) 

Recent pharmacovigilance events in the Union have shown the need for an automatic 
procedure at Union level in the cases of specific safety issues to ensure that a matter is 
assessed  and  addressed  in  all  Member  States  where  the  medicinal  product  is 
authorised. The scope of different Union procedures concerning nationally authorised 
products should be clarified. 

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 competent 
authorities  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. 

(3) 

Directive 2001/83/EC should therefore be amended accordingly. 

(4) 

Since  the  objective  of  this  Directive  to  harmonise  the  rules  on  pharmacovigilance 
across  the  Union  cannot  be  sufficiently  achieved  by  the  Member  States  and  can 

1 
2 
3 

OJ C , , p. . 
OJ C , , p. . 
OJ C , , p. . 

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therefore  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 
Directive does not go beyond what is necessary in order to achieve this objective, 

HAVE ADOPTED THIS DIRECTIVE: 

Directive 2001/83/EC is amended as follows: 

Article 1 

(1) 

In Article 23a, the second subparagraph is replaced by the following: 

"The  holder  shall  also  notify  the  competent  authority  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  competent  authorities  of  the  reasons  for  such  action  in 
accordance with Article 123." 

(2) 

Article 31 is replaced by the following: 

"Article 31 

1. The Member States, the Commission, the applicant or the marketing authorisation 
holder shall, in specific cases where the interests of the Union are involved, refer the 
matter to the Committee for application of the procedure laid down in Articles 32, 33 
and 34 before any decision is reached on an application for a marketing authorisation 
or  on  the  suspension  or  revocation  of  a  marketing  authorisation,  or  on  any  other 
variation of the marketing authorisation which appears necessary. 

Where the referral results from the evaluation of data relating to pharmacovigilance 
of  an  authorised  medicinal  product, 
the 
Pharmacovigilance Risk Assessment Committee and Article 107j(2) may be applied. 
The  Pharmacovigilance  Risk  Assessment  Committee  shall  issue  a  recommendation 
according to the procedure laid down in Article 32. The final recommendation shall 
be  forwarded  to  the  Committee  for  Medicinal  Products  for  Human  Use  or  to  the 
coordination group, as appropriate, and the procedure laid down in Article 107k shall 
apply. 

the  matter  shall  be  referred 

to 

However, where one of the criteria listed in Article 107i(1) is met, the procedure laid 
down in Articles 107i to 107k shall apply. 

2. Where the referral to the Committee concerns a range of medicinal products or a 
therapeutic class, the Agency may limit the procedure to certain specific parts of the 
authorisation.  

In  that  event,  Article  35  shall  apply  to  those  medicinal  products  only  if  they  were 
covered by the authorisation procedures referred to in this Chapter. 

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Where  the  scope  of  the  procedure  initiated  under  this  Article  concerns  a  range  of 
medicinal products or therapeutic class, medicinal products authorised in accordance 
with Regulation (EC) No 726/2004 which belong to that range or class shall also be 
included in the procedure." 

(3) 

In Article 34(3), the following subparagraph is added: 

"Where  the  scope  of  the  procedure  includes  medicinal  products  authorised  in 
accordance with Regulation (EC) No 726/2004 pursuant to the third subparagraph of 
Article  31(2)  of  this  Directive,  the  Commission  shall  where  necessary  adopt 
decisions to vary, suspend, revoke or refuse renewal of the marketing authorisations 
concerned." 

(4) 

Article 107i(1) is replaced by the following: 

"1. A Member State or the Commission, as  appropriate, shall initiate the procedure 
provided for in this section, by informing the other Member States, the Agency and 
the Commission, in any of the following cases: 

(a) it considers suspending or revoking a marketing authorisation; 

(b) it considers prohibiting the supply of a medicinal product; 

(c) it considers refusing the renewal of a marketing authorisation; 

(d)  it  is  informed  by  the  marketing  authorisation  holder  that,  on  the  basis  of  safety 
concerns, he has interrupted the placing on the market of a medicinal product or has 
taken action to have a marketing authorisation withdrawn, or that he intends to do so 
or has not applied for the renewal of a marketing authorisation; 

(e) it considers that a new contraindication, a reduction in the recommended dose, or 
a restriction to the indications is necessary. 

The  Agency  shall  verify  whether  the  safety  concern  relates  to  medicinal  products 
other  than  the  one  covered  by  the  information,  or  whether  it  is  common  to  all 
products belonging to the same range or therapeutic class. 

Where the medicinal product involved is authorised in more than one Member State, 
the  Agency  shall  without  undue  delay  inform  the  initiator  of  the  procedure  of  the 
outcome of this verification, and the procedures laid down in Articles 107j and 107k 
shall  apply.  Otherwise,  the  safety  concern  shall  be  addressed  by  the  Member  State 
concerned. The Agency or the Member State, as applicable, shall make information 
that the procedure has been initiated available to marketing authorisation holders." 

(5) 

Article 123(2) is replaced by the following: 

"2.  The  marketing  authorization  holder  shall  be  obliged  to  notify  Member  States 
forthwith  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 

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in  Articles  116  and  117.  In  such  case,  Member  States  shall  ensure  that  this 
information is brought to the attention of the Agency." 

Article 2 

1. 

Member  States  shall  bring  into  force  the  laws,  regulations  and  administrative 
provisions necessary to comply with this Directive by [12 months after publication in 
the  Official  Journal;  exact  date  inserted  at  time  of  publication]  at  the  latest.  They 
shall forthwith communicate to the Commission the text of those provisions. 

When  Member  States  adopt  those  provisions,  they  shall  contain  a  reference  to  this 
Directive  or  be  accompanied  by  such  a  reference  on  the  occasion  of  their  official 
publication. Member States shall determine how such reference is to be made. 

2. 

Member States shall communicate to the Commission the text of the main provisions 
of national law which they adopt in the field covered by this Directive. 

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

Article 3 

Article 4 

This Directive is addressed to the Member States. 

Done at Brussels, 10.2.2012 

For the European Parliament 
The President 

For the Council 
The President 

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