COMMISSION STAFF WORKING DOCUMENT IMPACT ASSESSMENT Accompanying document to the Proposal for a Regulation of the European Parliament and of the Council on the fees payable to the European Medicines Agency (EMA) for the conduct of pharmacovigilance activities in respect of medicinal products for human use
Date: 2013-06-26
Institutions: European Commission
Subjects: European Medicines Agency, drug surveillance, market approval, medicinal product, product safety, single market

EUROPEAN 
COMMISSION 

Brussels, 26.6.2013  
SWD(2013) 234 final 

COMMISSION STAFF WORKING DOCUMENT 

IMPACT ASSESSMENT 

Accompanying document to the  

Proposal for a Regulation of the European Parliament and of the Council on the fees 
payable to the European Medicines Agency (EMA)  for the conduct of 
pharmacovigilance activities in respect of medicinal products for human use 

{COM(2013) 472 final} 
{SWD(2013) 235 final}

EN 

   EN 

 
 
 
 
 
  
 
COMMISSION STAFF WORKING DOCUMENT 

IMPACT ASSESSMENT 

Accompanying document to the  

Proposal for a Regulation of the European Parliament and of the Council on the fees 
payable to the European Medicines Agency (EMA)  for the conduct of 
pharmacovigilance activities in respect of medicinal products for human use 

1. 

2. 

3. 

3.1. 

3.2. 

3.3. 

3.4. 

Introduction .................................................................................................................. 7 

Procedural issues and consultation of interested parties .............................................. 8 

Problem definition........................................................................................................ 9 

Context ......................................................................................................................... 9 

Inexistence of financial instrument to implement the legislation and inadequate 
funding for pharmacovigilance activities at the level of the EU................................ 11 

Lack of transparency and clarity in current situation of pharmacovigilance fees 
across Europe ............................................................................................................. 11 

Baseline scenario – how will the situation evolve if fees for Union-wide 
pharmacovigilance activities are not introduced........................................................ 13 

3.5. 

Subsidiarity analysis and right to act at EU level ...................................................... 14 

4. 

5. 

6. 

6.1. 

6.2. 

6.3. 

6.4. 

6.5. 

7. 

Objectives................................................................................................................... 14 

Options ....................................................................................................................... 15 

Assessment of impact of the options.......................................................................... 19 

Option 1: No change to the current situation ............................................................. 20 

Option 2: One annual flat fee covering all pharmacovigilance activities at EU level20 

Option 3: A combination of separate fees for procedure based activities and an 
annual flat fee for all other activities at EU level....................................................... 22 

Option 4: Only procedure-based fees......................................................................... 23 

Comparison of the options ......................................................................................... 24 

Monitoring and Evaluation ........................................................................................ 25 

Annex 1 - List of Abbreviations............................................................................................... 27 

Annex 2 – Summary of the Public Consultation...................................................................... 29 

Annex 3 – Pharmacovigilance activities at EU level: short description and estimated costs .. 37 

Annex 4 – Calculation of the amount of fees for considered options ...................................... 47 

Annex 5 – SMEs aspects of the assessment ............................................................................. 56 

Annex 6 – Provisions of the 2010 pharmacovigilance legislation relating to fees .................. 59 

Annex 7 – Assessment criteria and the impact of individual options ...................................... 61 

EN 

2 

   EN 

 
 
Annex 8 – Wider context of the initiative ................................................................................ 71 

Annex 9 – Assigning importance to the assessment criteria.................................................... 74 

EN 

3 

   EN 

 
 
Why? What is the problem being addressed?  

Summary of the report 

A. Need for action 

The  2010  EU  legislation  on  pharmacovigilance1  has  become  applicable  in  July  2012.  It  streamlines  the  post-
authorisation assessment and safety monitoring of medicines ('pharmacovigilance') for human use in the EU and 
significantly widens  the  tasks of  the  European  Medicines  Agency  (EMA)  with  regard  to  pharmacovigilance,  for 
both nationally and centrally authorised medicinal products, i.e. more than 350.000 products. These new tasks 
entail new costs for the EMA that need to be financed. The 2010 Pharmacovigilance legislation provides for fees 
to  be  charged  by  the  EMA  to  marketing  authorisation  holders  (MAH)  to  finance  those  pharmacovigilance 
activities carried out at EU level. The introduction of such fees requires legislative action which is the subject of 
this impact assessment.  

What is this initiative expected to achieve?  

The  general  objective  is  to  define  the  structure  and  the  level  of  the  fees  to  be  charged  to  MAH  for 
pharmacovigilance  activities  performed  at  the  EU  level  so  that  EMA  can  cover  its  costs  including  the 
remuneration of rapporteurs from Member States (MS) for their assessment work. 

The specific objectives are:  

• 
• 

• 

to ensure an adequate funding for pharmacovigilance activities at EU level, 
to establish a transparent, activity-based and cost-based fee system for the pharmacovigilance activities 
which are carried out at EU level, 
to define the structure of pharmacovigilance fees to reflect the principles of the 2010 Pharmacovigilance 
legislation. 

What is the value added of action at the EU level?  

The EMA is a decentralised agency of the European Union established by Regulation (EC) No 726/2004 and 
hence the decision on its funding and charging of fees can only be taken at the level of the EU. Therefore, only 
the Union can act to enable EMA to charge fees for pharmacovigilance.  

What  legislative  and  non-legislative  policy  options  have  been  considered?  Is  there  a  preferred 
choice or not? Why? Maximum 14 lines  

B. Solutions 

New  fees  can  only  be  introduced  via  legislative  action,  hence  non-legislative  policy  options  have  not  been 
considered. Legislative policy options that have been considered are:  

Option 1 (baseline) – no change to the current situation (no introduction of fees for pharmacovigilance) 

Option 2 - an annual flat fee charged to all authorised products in the EU 

Option  3  -  a  combination  of  separate  fees  for  procedure-based  activities  (charged  to  products  subject  to  a 

1 Regulation (EU) No 1235/2010 amending Regulation (EC) No 726/2004 and Directive 2010/84/EU amending Directive 2001/83/EC 

EN 

4 

   EN 

 
 
 
 
 
 
 
 
 
 
                                                 
specific  procedure  for  pharmacovigilance)  and  an  annual  flat  fee  for  all  other  activities  (charged  to  authorised 
products in the EU) 

Option 4 - procedure-based fees only. 

The preferred choice that has been identified is option 3, because a combination of procedure-based fees and 
an annual flat fee has been considered to be the most transparent, cost-based, activity-based and proportionate 
way of setting the new fees, in order to cover the costs of the pharmacovigilance activities at EU level. In this 
way, the products being part of a pharmacovigilance procedure at EU level will contribute to the financing of the 
cost of that procedure. At the same time, the costs of general pharmacovigilance activities of the EMA, and only 
that  part  of  the  cost,  would  be  covered  through  an  annual  flat  fee  charged  for  authorised  products  in  the  EU 
which benefit from the EU pharmacovigilance system.  

Who supports which option?  

The  EMA  favours  option  2,  an  annual  flat  fee.  The  position  of  industry  is  not  explicit  in  terms  of  one  single 
position  on  the  matter.  For  example,  the  European  organisation  representing  the  pharmaceutical  originator 
industry has expressed a preference for an annual flat fee, whereas the European organisation representing the 
generic industry is not in favour of that option. 

The  main  interest  of  the  national  competent  authorities  of  the  MS  is  to  ensure  remuneration  for  rapporteurs 
providing  scientific  assessment  within  the  Union-wide  pharmacovigilance  procedures.  This  is  the  case  of  all 
options involving policy action. 

What are the benefits of the preferred option (if any, otherwise main ones)?  

C. Impacts of the preferred option 

Only  the  MAHs  whose  products  are  involved  in  EU  pharmacovigilance  procedures  would  pay  for  these 
procedures. As to the annual flat fee component, the estimated cost of specific pharmacovigilance procedures 
will not be included.  

The rapporteurs from MS would receive remuneration for their services according to a fixed scale, based on the 
average workload and costs per type of procedure.  

The annual flat fee would be lower than in option 2, only covering non-procedure-related costs. Such a structure 
of the fees would thus be perceived by stakeholders as the most transparent and proportionate option and the 
fairest  fee  model  in  the  context  created  by  the  2010  legislation  on  pharmacovigilance.  This  option  would  also 
take  into  account  the  requests  of  the  Court  of  Auditors  and  the  European  Parliament  for  a  cost-based 
remuneration of MS rapporteurs.  

What are the costs of the preferred option (if any, otherwise main ones)?  

Irrespective of the option chosen, the overall cost of the new 2010 pharmacovigilance legislation is estimated at 
€ 38.5 m (€ 28 m for the EMA and € 10.5 m for rapporteurs from the MS). 

How will businesses, SMEs and micro-enterprises be affected?  

Under  the  preferred  option,  the  effect  on  businesses  would  be  the  most  proportionate,  as  they  would  pay  for 
procedures  only  if  and  when  they  are  involved  in  a  procedure  (procedure-based  fees).  The  annual  flat  fee, 
affecting potentially all businesses, would only cover the cost of general pharmacovigilance activities of EMA. All 

EN 

5 

   EN 

 
 
 
 
 
 
 
 
 
  
 
fees would be set to cover the respective estimated costs.  

Small and medium-sized companies would pay 60% of the fees and micro-enterprises would be excluded from 
the payment of fees. 

20%  reduction  of  the  annual  flat  fee  would  be  granted  to  authorised  generics,  homeopathic,  herbal  and  well-
established use products, as these products are expected do have a well-established safety profile and should 
thus not be subject to the full fees. 

Will there be significant impacts on national budgets and administrations?  

As work is shifted from national to EU level with the new pharmacovigilance legislation, it is reasonable to expect 
that national fees would be readjusted if necessary, in order to reflect this change. 

Will there be other significant impacts?  

The number of authorisations would be taken into account in the charging of the procedure-based fee and the 
annual flat fee. However, the impact is difficult to foresee as it will depend on a number of factors, such as the 
type of products in the portfolio and the number of authorisations. 

When will the policy be reviewed?  

D. Follow up 

The  effect  of  the  introduction  of  fees  for  pharmacovigilance  would  need  to  be  monitored  by  the  Commission 
based on information provided by the EMA. The European Commission may adjust, if necessary, the amounts of 
the fees. 

EN 

6 

   EN 

 
 
 
 
1.  INTRODUCTION 
All  medicinal  products  for  human  use  have  to  be  authorised  either  at  Member  State  or  EU 
level  before  they  can  be  placed  on  the  EU  market.  A  strict  testing  and  assessment  of  their 
quality, safety and efficacy is required before such authorisation is issued. In addition, once a 
medicinal product has been authorised and placed on the market in the EU, it continues to be 
monitored throughout its entire lifespan in order to ensure that any aspect which could impact 
the  safety  profile  of  such  medicine  is  detected  and  assessed  and  that  necessary  measures, 
possibly  including  the  withdrawal  from  the  market,  are  taken.  This  process  and  science  of 
monitoring  the  safety  of  medicines  and  taking  action  to  reduce  the  risks  and  increase  the 
benefits of medicines is called pharmacovigilance. 

The EU pharmacovigilance system is one of the most advanced and comprehensive systems 
in  the  world  and  represents  a  robust  and  transparent  instrument  to  ensure  a  high  level  of 
public health protection throughout the Union. The legal framework of pharmacovigilance for 
medicines  marketed  within  the  EU  is  provided  for  in  Regulation  (EC)  No  726/2004  (the 
Regulation)2  and  in  Directive  2001/83/EC  (the  Directive)3.  The  EU  pharmacovigilance 
legislation  has  been  subject  to  a  major  review  and  a  comprehensive  impact  assessment  that 
lead  to  the  adoption  of  a  revised  legislation  in  20104  (the  2010  Pharmacovigilance 
legislation),  which  strengthens  and  rationalises  the  system  for  monitoring  the  safety  of 
medicines  on  the  European  market.  This  legislation  provides  for  a  number  of  EU-wide 
procedures  to  assess  pharmacovigilance  data  which  may  lead  to  regulatory  action.  Some 
additional amendments were made to the pharmacovigilance legislation in 2012 following the 
Mediator-case5.  

the  EU-wide  post-authorisation 
legislation  streamlines 
The  2010  pharmacovigilance 
assessment  and  monitoring  of  medicines  and  significantly widens the tasks of the European 
Medicines  Agency  (EMA)  with  regard  to  pharmacovigilance,  irrespective  of  how  the 
medicinal  products  have  been  authorised.  Therefore,  the  EMA  has  pharmacovigilance 
competences  for  both  nationally  and  centrally  authorised  medicines.  To  finance  these 
activities,  the  2010  Pharmacovigilance  legislation  provides  for  fees  to  be  charged  to 
marketing  authorisation holders (MAH). These  fees would not cover  the pharmacovigilance 
activities of the National competent authorities (NCA) at national level whilst remuneration of 
the rapporteurs for scientific evaluations within the framework of the EU procedures would be 
included 
to  charge  fees  for 
the  proposed  fees.  MS  may 
pharmacovigilance activities at national level.   

therefore  continue 

in 

Since  the  2010  Pharmacovigilance  legislation  only  concerns  medicinal  products  for  human 
use, the current proposal on pharmacovigilance fees can only concern medicinal products for 
human use. 

This  impact  assessment  report  evaluates  the  various  options  for  charging  the  fees  to  MAHs  
for  the  pharmacovigilance  activities  carried  out  by  the  EMA.  It  does  not  evaluate  the 

2 OJ L 136, 30.4.2004, p. 1) 
3 OJ L 348 on 31 December 2010 
4 Regulation (EU) No 1235/2010 amending Regulation (EC) No 726/2004 and Directive 2010/84/EU amending 
Directive 2001/83/EC 
5  Regulation  (EU)  No  1027/2012  amending  Regulation  (EC)  No  726/2004  [OJ  L  316/38,  14.11.2012]  and 

Directive 2012/26/EU amending Directive 2001/83/EC [OJ L 229/1, 27.10.2012]. 

EN 

7 

   EN 

 
 
 
 
 
                                                 
pharmacovigilance  legislation  as  such,  as  this  evaluation  took  place    during  the  impact 
assessment  of  the  legal  proposal  which  lead  to  the  adoption  of  the  2010  pharmacovigilance 
legislation. 

2.  PROCEDURAL  ISSUES  AND  CONSULTATION  OF  INTERESTED 

PARTIES 

As  part  of  the  preparation  of  a  legal  proposal  on  pharmacovigilance  fees,  DG  SANCO  in 
close collaboration with the EMA drafted a concept paper6 for public consultation. Given that 
the pharmacovigilance procedures foreseen in the 2010 pharmacovigilance legislation are new 
procedures,  the  concept  paper  used  existing  procedures  that  were  considered  sufficiently 
similar as benchmarks for the new procedures. In addition, a pharmacovigilance service fee to 
be charged on an annual basis was considered in the paper in order to cover those activities of 
EMA that benefit industry in general, but for which it is not possible (or at least very difficult) 
to identify individual addressee(s). 

Public Consultation 

The Commission launched the public consultation on 18 June 2012 with a deadline for replies 
on 15 September 2012. In total, 85 replies were received (mainly from industry, but also from 
the  Member  States  and  other  stakeholders).  The  summary  of  the  replies  to  the  public 
consultation is attached as Annex 2 and was also published on the DG SANCO website on 29 
November  20127.  In  general,  the  comments  were  overall  negative  notably  as  regards  the 
amounts  proposed.  They  were  considered  to  be  too  high  and  without  sufficient  justification 
and  transparency  as  regards  the  workload  and  costs.  Grouping  of  MAHs,  especially  for 
submitting  a  single  periodic  safety  update  report  (PSUR),  was  considered  by  many  as  not 
applicable  in  practice8.  Many  respondents  questioned  the  benchmarks  that  were  used  and 
considered  that  pharmacovigilance  fees  should  rather  be  based  on  the  time  spent  and  the 
associated  costs  for  the  work.  Several  industry  respondents  flagged  the  risk  of  possible 
duplicative  charging  of  EMA  and  the  Member  States,  given  that  many  of  the  competent 
authorities  in  the  Member  States  currently  charge  fees  for  pharmacovigilance.  Particular 
concerns  were  expressed  by  SMEs,  stating  that  despite  the  proposed  fee  reductions  in  the 
concept  paper,  the  amounts  were  still  too  high.  Also  many  responses  from  industry 
associations,  representing  the  generics,  homeopathics,  herbals,  and  products  authorised  on 
grounds  of  well-established  use,  considered  that  the  proposed  fees  would  unfairly  affect 
MAHs with a large portfolio of products with well-established safety profiles.  

As  a  result  of  these  comments,  tis  impact  assessment  was  based  on  an  evaluation  of  the 
workload and costs involved. The options (i.e. the structure and the level of the fees) in this 
impact assessment have been assessed accordingly. 

6 http://ec.europa.eu/health/files/pharmacovigilance/2012-06_concept_paper_en.pdf 
7 http://ec.europa.eu/health/human-use/pharmacovigilance/developments/2012-11_phv_fees_en.htm 
8 See also a special section on grouping in Annex 4. 

EN 

8 

   EN 

 
 
 
 
 
                                                 
Impact Assessment Steering Group 

An  Impact  Assessment  Steering  Group  has  met  five  times  on  20  January  2012,  13  March 
2012, 11 May 2012, 19 November 2012 and 1 March 2013. The DGs invited to the meetings 
were SG, DG BUDG, DG ENTR, DG RTD, DG COMP, DG TRADE, DG ECFIN and LS. 
The EMA participated at these meetings, as well as in a number of other bilateral meetings 
with DG SANCO, in order to prepare this impact assessment.  

3.  PROBLEM DEFINITION 

3.1. 

Context  

All medicinal products in the EU are subject to a strict testing and assessment of their quality, 
efficacy  and  safety  before  being  authorised.  Once  placed  on  the  market  they  continue  to  be 
monitored so that any aspect which could impact the safety profile of a medicine is detected 
is  called 
and  assessed  and 
pharmacovigilance.  

that  necessary  measures  are 

taken.  This  monitoring 

Pharmacovigilance  is  the  process  and  science  of  monitoring  the  safety  of  medicines  and 
taking  action  to  reduce  the  risks  and  increase  the  benefits  of  medicines.  In  general,  the 
pharmacovigilance activities include:  

•  Collecting and managing data on the safety of medicines  
•  Looking at the data to detect 'signals' (any new or changing safety issue)  
•  Evaluating the data and making decisions with regard to safety issues  
•  Pro-active risk management to minimize any potential risk associated with the use of 

the medicine  

•  Acting to protect public health (including regulatory action)  
•  Communicating with and informing stakeholders and the public  
•  Audit, both of the outcomes of action taken and of the key processes involved.  

Stakeholders directly involved in pharmacovigilance include:  

•  Patients who are the users of medicines  
•  Doctors, pharmacists, nurses and all other health care professionals working with 

medicines  

•  Regulatory authorities, including the EMA and those in the Member States responsible 

for monitoring the safety of medicines  

•  Pharmaceutical companies and companies importing or distributing medicines.  

Further description of Union-wide pharmacovigilance activities is provided in Annexes 3 and 
4. 

The revision of the Pharmacovigilance legislation 

A major revision of the EU legislation on pharmacovigilance was introduced in 2010 through 
the  adoption  of  (a)  Regulation  (EU)  No  1235/2010  of  the  European  Parliament  and  of  the 
Council  amending,  as  regards  pharmacovigilance  of  medicinal  products  for  human  use, 

EN 

9 

   EN 

 
 
 
 
Regulation No 726/2004 and (b) Directive 2010/84/EU of the European Parliament and of the 
Council amending, as regards pharmacovigilance, Directive 2001/83/EC.  

The  main  pillars  of  the  new  2010  pharmacovigilance  legislation  are  proactive  and 
proportionate  risk  management,  higher  quality  of  safety  data,  stronger  link  between  safety 
assessments  and  regulatory  action,  strengthened  transparency,  communication  and  patient 
involvement, clear tasks and responsibilities for all parties (marketing authorisation holders, 
competent  authorities,  EMA),  improved  EU  decision-making  procedures  (harmonised 
decisions and efficient use of resources) and the establishment of a new scientific committee 
at the EMA - the Pharmacovigilance Risk Assessment Committee (PRAC). 

The new legislation became applicable in July 2012. The changes affect CAPs and non-CAPs. 
Given that the 2010 pharmacovigilance legislation provides a greater role for EMA in the area 
of  pharmacovigilance  in  general,  i.e.  irrespective  of  how  the  medicinal  products  have  been 
authorised (therefore including both nationally and centrally authorised products), EMA will for 
the first time be able to charge fees also for nationally authorised products.   

Some additional amendments to the pharmacovigilance legislation were adopted in 2012. As a 
result  of  these  amendments,  it  will  be  possible  for  a  medicine  to  be  withdrawn  EU-wide  if 
serious safety problems become apparent. A new automatic urgency procedure will include an 
EU  safety  evaluation  if  one  Member  State  decides  that,  on  the  basis  of  pharmacovigilance 
activities,  a  medicine  should  be  withdrawn  from  its  own  market.  In  addition,  the  list  of 
products that are automatically subject to additional monitoring has been extended to include 
products that have the following post authorisation safety conditions: post authorisation safety 
studies, conditional or exceptional marketing authorisations. 

Existing Fees and Financing of the EMA activities  

The EMA budget for 2012 was €223,5 million of which €183 million stems from fees and €39 
million from the EU budget.  
Fees  are  currently  charged  by  the  EMA  in  accordance  with  Council  Regulation  (EC)  No 
297/95  on  fees  payable  to  the  EMA  for  the  Evaluation  of  Medicinal  Products  ('Fees 
Regulation')9.  The  Fees  Regulation  sets  out  fees  for  centrally  authorised  products  (CAPs) 
including  an  annual  fee  (the  full  fee  is  currently  €  95  900).  For  the  appl ication  of  the  Fees 
Regulation, there are Implementing Rules adopted by the Management Board of the EMA10. 
According to those rules, the annual fee revenue may be used for the following activities for 
CAPs: 

•  30% is meant to cover the EMA pharmacovigilance and inspection staff costs,  
•  30%  is  meant  to  cover,  inter  alia,  the  rapporteur  and  co-rapporteurs  work,  where 
applicable,  of  scientific  evaluation  services  provided  at  the  request  of  EMA,  e.g. 
annual  product  reports  and  specific  reporting  for  pharmacovigilance  and  safety 
reports. 

9 OJ L 35, 15.2.1995 p.1 
10  Article  65  of  Regulation  (EC)  No  726/2004  stipulates  that  the  Management  Board  shall  consist  of  one 
representative  of  each  Member  State,  two  representatives  of  the  Commission  and  two  representatives  of  the 
European  Parliament.  In  addition,  two  representatives  of  patients'  organisations,  one  representative  of  doctors' 
organisations  and  one  representative  of  veterinarians'  organisations  shall  be  appointed  by  the  Council  in 
consultation with the European Parliament on the basis of a list drawn up by the Commission. 

EN 

10 

   EN 

 
 
 
 
                                                 
•  30%  is  meant  to  be  attributed  to  special  activities,  to  be  determined  by  the  EMA 
Management board, which also may have a link to pharmacovigilance for CAPs.   

Whereas  the  previous  (2004)  wording  of  Article  67  of  the  Regulation  provided  that 
pharmacovigilance activities are to be publicly funded, the revised Regulation (as amended by 
the 2010 pharmacovigilance legislation) provides that industry is to be charged fees by EMA 
for the conduct of pharmacovigilance activities. In order to enable EMA to charge such fees, 
there is a need for a legal instrument. 

The  specific  problems  related  to  the  absence  of  fees  for  pharmacovigilance  activities  are 
outlined in the following chapters.  

3.2. 

Inexistence  of  financial  instrument  to  implement  the  legislation 
and  inadequate  funding  for  pharmacovigilance  activities  at  the 
level of the EU 

Funding of EMA pharmacovigilance activities became inadequate due to the introduction of 
new tasks in the 2010 pharmacovigilance legislation. Prior to this legislation, the EMA was 
only tasked with pharmacovigilance of centrally authorised products. The new legislation has 
substantially  increased  the  scope  of  EMA  competence  in  pharmacovigilance,  by  including 
also  products  which  are  authorised  via  national  procedures  (i.e.  mutual  recognition, 
decentralised  procedure,  purely  national  procedures).  The 
logic  of  EU-wide 
pharmacovigilance  assessments  per  substance,  regardless  of  the  number  of  products 
corresponding to this substance (or the procedure under which they have been authorised) that 
are on the EU/EEA market, leads to a substantial workload associated with the corresponding 
Union-wide  procedures  and  activities.  Furthermore,  the  EU-wide  assessments  require 
designing,  setting  up,  populating,  maintaining  and  exploiting  EU-wide  databases  of  all 
authorisations  (detailed  description  of  the  product  and  its  authorised  use)  of  medicinal 
products  for  human  use  in  the  EU/EEA,  including  all  subsequent  variations  to  those 
authorisations, adverse drug reactions declared for those products, as well as a repository for 
all individual periodic safety update reports drawn up for those products. 

The  legal  instrument  that  would  enable  EMA  to  charge  fees  for  the  pharmacovigilance 
activities laid down in the 2010 pharmacovigilance legislation is missing. As a consequence, 
the  existing  fee  structure  of  EMA  does  not  reflect  the  requirements  set  out  in  the  2010 
pharmacovigilance  legislation  and  there  is  no  adequate  funding  for  pharmacovigilance 
activities  at  EU  level.  In  particular,  the  EMA  is  not  in  a  position  to  finance  the  full 
implementation  of  the  new  legislation.  This  has  direct  consequences  as  regards  rapporteurs 
and  co-rapporteurs  from  the  national  competent  authorities  in  the  MS,  i.e.  the  absence  of 
remuneration  for  their  assessment  work  within  the  Union-wide  procedures.  This  situation  is 
unsustainable even in the short term. 

3.3. 

Lack  of  transparency  and  clarity  in  current  situation  of 
pharmacovigilance fees across Europe 

The existing fees for pharmacovigilance activities in the EU do not reflect the requirements 
and parameters set out in the 2010 pharmacovigilance legislation.  

EN 

11 

   EN 

 
 
 
 
 
 
 
  
At the level of the EMA, as described above, there are no specific fees for the financing of the 
EMA's pharmacovigilance activities provided for in the 2010 pharmacovigilance legislation. 

At  the  level  of  Member  States  and  prior  to  application  of  the  2010  pharmacovigilance 
legislation, the pharmacovigilance activities of non-centrally authorised products was carried 
out by the individual national agencies, such as assessments of periodic safety update reports 
for products authorised in the MS.  The financing of these activities follow different models 
decided  at  national  level,  e.g.  through  specific  pharmacovigilance  fees  (e.g.  fee  for  periodic 
safety update reports), generic (annual) fees, possible inclusion in authorisations fees, possible 
financing through national budgets, etc. Table 1 provides an indicative overview of national 
fee  structures12.  There  were  no  EU-wide  assessment  procedures  with  the  exception  of 
pharmacovigilance  (safety)  referrals,  though  under  a  different  legal  framework.  Under  the 
new  pharmacovigilance  legislation,  automatically  triggered  pharmacovigilance  referrals  are 
expected to lead to a substantial assessment workload.   

The Commission's proposal for the 2010 pharmacovigilance legislation, was accompanied by 
a  Financial  Statement11  according  to  which  all  costs  related  to  activities  resulting  from  the 
legislative proposal are to be covered through fees. Many NCAs currently charge the MAHs 
for pharmacovigilance activities, and hence there is also a need to ensure that MAHs are not 
charged  twice  for  the  same  work.  The  2010  legislation  provides  for  pharmacovigilance 
assessments  (i.e.  pharmacovigilance  referrals,  PSUR  assessments,  PASS  assessments)  to  be 
performed at EU level. Therefore, national fees should not cover those assessments. The non-
procedure-related  pharmacovigilance 
the  2010 
pharmacovigilance  legislation  which  also  benefit  the  network,  e.g.  those  relating  to  the  EU 
database on adverse drug reactions, should only be charged for at the level of the EMA. 

the  EMA  under 

activities  of 

However, NCAs may still include in their national fees the costs for their own activity related 
to  pharmacovigilance,  e.g.  collecting  and  transmitting  to  the  EMA  pharmacovigilance 
information.  In  addition,  the  NCAs  will  continue  to  carry  out  some  pharmacovigilance 
activities for NAPs, such as signal detection (which EMA is doing for CAPs) as well as the 
assessment  of  those  PASS  which  are  conducted  only  in  one  MS  (as  PASS  which  are 
conducted in more than one MS will be subject to the EU-wide procedures and thus covered 
by  the  fees  charged  by  EMA).  As  the  EU-wide  activities  which  are  to  be  covered  by  the 
proposed  pharmacovigilance  fees  will  be  defined,  it  is  reasonable  to  expect  that  NCAs  will 
not  include  in  their  national  fees  pharmacovigilance  activities  that  are  not  (or  no  longer) 
performed at national level. 

The  various  national  fee  structures  may  be  adapted,  if  needed,  to  the  new  2010 
pharmacovigilance legislation only when the fees for pharmacovigilance levied by the EMA 
are actually introduced.  

It would be necessary for the NCAs to ensure that there is no double charging at national level 
of  the  activities  for  which  a  fee  is  charged  by  the  EMA.  To  this  end,  any  proposed  fees  of 
EMA should be transparent and well defined in order for MAHs and MS to be able to identify 
which pharmacovigilance activities these fees would cover.  

11 http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=COM:2008:0664:FIN:en:PDF. 

EN 

12 

   EN 

 
 
 
 
 
 
 
                                                 
Table 1: Pharmacovigilance fees charged by some NCA12 
PSUR fee MRP / 
DCP 

PSUR fee 
National 
procedure  

Annual 
Fee 

CMS 

RMS 

Austria 

Belgium 

Bulgaria  

Czech 
Republic 

Denmark  

Estonia 

Finland  

Germany 

Ireland 

Italy 

Latvia 

Lithuania 

Malta 

500 € 

500 € 

3.600 € 

1.211 € 

1.211 
€ 

2.422 € 

in Annual Fee 

489 € 

762 € 

871 € 

871 € 

1.742 € 

1.180 € 

320 € 

160 € 

1.200 € 

1.300 
€ 

4.400 € 

in Annual Fee 

in Annual Fee 

1.300 € 

in Annual Fee 

1.423 € 

273 € 

178 € 

1.143 € 

2.300 € 

11.750 
€ 

Netherlands 

in Annual Fee 

Slovenia 

Spain 

1.500 € 

375 € 

250 € 

375 € 

Sweden 

in Annual Fee 

UK 
Source: Web pages of NCAs in MS  

in Annual Fee 

812 € 

1.000 € 

500 € 

1.050 € 

118 € 

5.366 € 

28.520 € 

3.4. 

Baseline  scenario  –  how  will  the  situation  evolve  if  fees  for 
Union-wide pharmacovigilance activities are not introduced 

legislation, 

With an unchanged policy and thus no financial instrument in place for the implementation 
the  revised  pharmacovigilance 
there  would  be  a  growing  number  of 
pharmacovigilance procedures under the 2010 pharmacovigilance legislation for which there 
would  be  no  funding  available.  This  already  leads  to  difficulties  in  finding  rapporteurs  and 
co-rapporteurs, as the system has to operate currently on a non-remunerated basis. Moreover, 
apart  from  pharmacovigilance,  there  are  already  some  activities  involving  NCAs  and  the 
EMA  which  are  non-remunerated.  The  pharmacovigilance  procedures  which  represent  a 
considerable workload (e.g. an average of 600 PSUR assessments expected per year) would 
add further constraints to the system.  

In the absence of a change to the current situation, the future would be even less transparent, 
as the new legislation covers both CAPs and non-CAPs.  

As mentioned above, the MAHs holding CAPs pay currently an annual fee to EMA for each 
MA13.  The  annual  fee  revenue  of  EMA  and  the  actual  contribution  of  this  revenue  to  

12      Table  1  presents  a  non-exhaustive  and  indicative  view  of  the  level  of  fees  levied  at  the  level  of  Member 
States.  Despite  the  fact  that  data  is  not  available  from  all  NCAs,  available  data  suggests  that  there  are 
significant differences in the structure and level of national fees for pharmacovigilance.        

13 Article 3 paragraph 6 of the Fees Regulation 

EN 

13 

   EN 

 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
 
 
                                                 
pharmacovigilance  activities  for  CAPs  as  set  out  in  the  Implementing  Rules  of  the  Fees 
Regulation14 is being examined in detail based on information from the EMA. On the basis of 
this work, an adjustment with regards to the annual fee revenue may be necessary.    

Further projection of the baseline scenario is provided in section 6.1. 

3.5. 

Subsidiarity analysis and right to act at EU level 

The EMA is a decentralised Agency of the EU under the Regulation and hence the decision on 
its  funding  and  charging  are  to  be  taken  at  the  European  level.  The  new  pharmacovigilance 
legislation provides a legal base for EMA to charge fees for pharmacovigilance. Only the Union 
can  act  to  introduce  these  fees  for  pharmacovigilance.  As  mentioned  above,  the  proposed 
legislation will only deal with fees for EMA (and not fees charged by NCAs for which the EU is 
not competent).  

As to the legal instrument to be used, it should be noted that the current Fees Regulation is a 
Council Regulation,  that was last amended in 2005. Since the Treaty on the Functioning of the 
European  Union  became  applicable,  all  legislative  procedures  are  normally  based  on  the 
ordinary  legislative  procedure  (previously  'co-decision  procedure')  involving  both  the  Council 
and  the  European  Parliament.  For  legal  certainty,  it  is  proposed  to  create  for  EU 
pharmacovigilance  fees  a  separate  legal  instrument,  i.e.  a  Regulation  of  the  European 
Parliament  and  of  the  Council,  which  will  be  subject  to  the  ordinary  legislative  procedure 
(Article 294 of the TFEU).   

4.  OBJECTIVES 

The general objective which this initiative aims to contribute to, is to ensure a high level of 
human  health  protection  in  the  EU  as  well  as  to  promote  the  functioning  of  the  internal 
market.  

The  specific  objective  is  to  ensure  the  implementation  of  the  2010  pharmacovigilance 
legislation  through  defining    the  structure  and  the  level  of  the  fees  charged  by  the  EMA  to 
MAHs  for  Union-wide  pharmacovigilance  activities.  In  order  to  make  sure  that  adequate 
funding for those pharmacovigilance activities is available, such a fee structure/level should 
allow for the EMA to cover the estimated costs, including remuneration of rapporteurs from 
the  NCAs  for  the  assessment  they  provide.  It  should  also  underpin  the  establishment  of  a 
transparent,  activity  based  and  cost-based  fee  system  of  the  EMA  for  pharmacovigilance 
activities at EU level. 

The  operational  objectives  and  the  criteria  for  assessing  the  alternative  fee  systems  stem 
directly from the specific objectives of the initiative, i.e. to establish the appropriate structure 
and the level of fees for pharmacovigilance activities. They are as follows: 

1.  Transparency  –  i.e.  clear  relationship  between  the  type  and  level  of  fee  and  the 
corresponding  work  carried  out.  Fees  in  general  should  reflect  the  overall  average 
level of work required and should cover all the administrative, technical and scientific 
activities  provided  in  a  transparent  manner.  The  link  between  services  provided  and 
fee charged should be clear.  

14 The amount (or, in some cases, the range) of the existing fees are laid down in the current Fees Regulation, 
whereas the Implementing rules specify more precise amounts, exemptions and allocation of the fee revenue. 

EN 

14 

   EN 

 
 
 
 
 
 
 
                                                 
2.  Fairness  -      i.e.  the  notion  that  the  MAH  should  contribute  to  the  financing  of 
pharmacovigilance activities on the basis of potential safety concerns, recognising that 
not all products have the same safety profiles. Such an approach is also in line with the 
underlying  pharmacovigilance  legislation,  e.g.  where  the  frequency  of  PSUR 
submission  is  to  be  established  on  the  basis  of  the  safety  profile  (expected  risks)  of 
each concerned substance. The fee should therefore be constructed in a way aimed at 
ensuring  a  balance  between  the  amount  paid,  the  work  carried  out  and  the  potential 
risks. Another dimension of the fairness principle is to avoid cross-subsidisation and 
double charging as far as reasonably achievable.  

3.  Stability -   i.e. the need to provide for a stable pharmacovigilance  fee system at EU 
level  based  on  the  highest  possible  degree  of  financial  predictability  and  avoiding 
variable  remuneration  of  similar  scientific  services.  However,  given  that  the  2010 
pharmacovigilance  legislation  provides  for  EU-wide  procedures  which  cannot  be 
predicted with 100% certainty, a degree of uncertainty in respect of fee revenue and 
costs will remain.  

4.  Simplicity  –  i.e.  minimum  additional  administrative  complexity  and  burden.  This 
criterion is linked to the importance that the EU pharmacovigilance fee system be well 
accepted by stakeholders. A genuinely simple system is, however, difficult to achieve, 
given the complexity of the underlying legislation and the fact the EMA will, for the 
first time, charge MAHs holding non-centrally authorised products. 

5.  OPTIONS 

Several policy options to collect pharmacovigilance fees were considered. Fee reductions or 
waivers  foreseen  and  proposed  (e.g.  for  SMEs,  micro-enterprises)  are  part  of  the  individual 
options. The calculation of the amount of the fees for each option based on the estimated costs 
of the conducted pharmacovigilance activities is outlined in Annex 4.  

The SMEs reductions projected in the individual options are based on the comparisons of the 
added  value  per  employee  as  a  possible  measure  of  profitability  of  companies.  Using  this 
measure, small and medium enterprises in the pharmaceutical sector are on average 40 % less 
profitable than non-SMEs and accordingly it is proposed that these enterprises will pay 60 % 
of  the  standard  fee.  The  micro-enterprises  are  assumed  to  be  entirely  exempted  from  the 
obligation to pay parmacovigilance fees since the already small number of authorisations held 
by  SMEs  is  further  decreased  in  case  of  micro  enterprises  which  implies  that  the 
administration  burden  to  collect  the  fee  would  offset  the  benefits  from  its  collection. 
Exempting  micro-enterprises  would  thus  not  impair  the  objectives  of  the  initiative.  SME 
aspects and further justifications of the fee discounts is discussed in Annex 5.  

Option 1: No change to the current situation 

The  first  option  would  be  to  keep  the  current  situation  unchanged.  No  specific 
pharmacovigilance related fees to be charged by EMA would be introduced.   

EN 

15 

   EN 

 
 
 
 
 
 
 
 
 
 
 
 
Option 2: One flat fee covering all pharmacovigilance activities 

A  flat  fee  for  pharmacovigilance  activities  of  EMA  would  be  introduced  and  applicable 
annually  to  all  MAHs  having  at  least  one  medicinal  product  authorised  in  the  EU.  The  fee 
amount charged to each particular MAH would be calculated on the basis of chargeable units 
corresponding  either  to  individual  entries  in  the  EU  database  set  by  article  57(2)  of  
Regulation 726/2004 with respect to medicinal products (‘EV-codes’) related to that particular 
MAH, or to marketing authorisations defined at national level or to the MAH itself. The fee 
per  chargeable  unit  would  be  €  122  in  case  the  EV-code  is  chosen  as  such.  The  overall 
amount  of  fees  collected  would  on  average  cover  the  estimated  cost  of  all  Union-wide 
pharmacovigilance activities carried out in one year.  

Reductions  (fee  incentives)  for  certain  categories  of  MAHs,  such  as  SMEs  would  apply.  A 
decreased flat fee for  medicinal  products for which the MAH is a SME would be set at the 
level of 60 % of a full flat fee. No fee would be charged for medicinal products for which the 
MAH is a micro-enterprise.  

A  fee  reduction  of  20%  is  proposed  for  authorised  generics,  homeopathic,  herbals  and 
medicinal products authorised on grounds of well-established use15. A large portfolio of these 
products with a long history of use usually implies that their safety profile is well known and, 
consequently,  they  are  less  likely  to  be  subject  to  EU  pharmacovigilance  procedures.  With 
some  exceptions,  these  are  the  categories  of  products  which  are  normally  not  required  to 
submit  PSURs  under  the  2010  pharmacovigilance  legislation  and  this  approach  is  also 
consistent with the views expressed in the public consultation.  Finally, it should be noted that 
some  CAPs  such  as  generics  are  currently  subject  to  a  reduced  annual  fee  under  the  Fees 
Regulation.  

Option 3: A combination of separate fees for procedure-based activities and an annual flat 

fee for all other activities 

Two  separate  categories  of  fees  would  be  charged.  (1)  Different  fees  for  specific 
pharmacovigilance activities/procedures, i.e. for the assessment of PSURs, the assessment of 
the  PASSs  and  assessment  in  case  of  pharmacovigilance  referrals  would  be  charged  to  all 
MAHs having a medicinal product that is subject to the procedure in question.   Additionally, 
(2)  an  annual  flat  fee  would  be  charged  to  all  MAHs  having  at  least  one  medicinal  product 
authorised in the EU. This additional fee would cover only the costs of the activities of EMA 
other that those related to the specific procedures.  
The overall amount of fees collected would cover on average the estimated cost of all Union-
wide pharmacovigilance activities.  

A fixed overall fee amount per PSUR assessment procedure would be based on its estimated 
average cost of €  19  484. The division  of th e  fee  among  the  MAHs  would  be  based  on  the 
proportion of chargeable units (e.g. EV-codes) related to each MAH whose product is subject 
to the procedure compared to all other MAHs involved in the procedure. 

A  fixed  overall  fee  amount  per  PASS  assessment  would  be  based  on  its  estimated  average 
this amount will be divided by the number of 
cost of € 42 962. In the case of joint studies, 

15 Products which have been registered at national level under the procedure laid down in Chapters 2 and 2a of 
Directive 2001/83/EC are excluded from the fee. 

EN 

16 

   EN 

 
 
 
 
  
 
 
 
                                                 
marketing authorisation holders that have submitted the joint study in order to constitute the 
individual amount payable by this entity (i.e. the MAH).  

A  fixed  overall  fee  amount  per  pharmacovigilance  referral  will  be  based  on  its  estimated 
average cost of € 168 542. As with the PSUR  assessment, the division of the fee among the 
MAHs  would  be  based  on  the  proportion  of  chargeable  units  related  to  each  MAHs  having 
products that are involved in the procedure.  

The annual flat fee for the pharmacovigilance activities not directly related to any of the three 
procedures  above  would  be  based  on  the  estimated  cost  of  those  activities  and  charged 
annually to all MAHs having medicinal products authorised in the EU, with some exceptions 
explained below. The total amount charged to a particular MAH would be calculated on the 
basis  of  chargeable  units  related  to  that  particular  MAH.  Should  the  EV-code  be  used,  the 
amount  would be € 60.  

Given  that  the  new  pharmacovigilance  activities  to  be  carried  out  at  the  EU  level  relate  to 
both CAPs and non-CAPs for the benefit of all marketing authorisation holders in the EU, the 
holders of medicinal products authorised in the EU should contribute to the financing of these 
activities. It is proposed that MAHs of CAPs be exempted from the payment of the envisaged 
annual  flat-fee  component  of  the  pharmacovigilance  fees,  as  they  already  pay  to  EMA  the 
annual fee applicable to CAPs under the existing Fees Regulation.  

Reductions  (fee  incentives)  for  SMEs  would  apply  both  to  the  annual  flat  fee  and  to  the 
procedure-based fees. MAHs that are SME would be charged 60 % of the applicable full fee 
and no fee would be charged for medicinal products for which the MAH is a micro-enterprise. 

In  respect  of  the  flat  fee  component,  a  fee  reduction  of  20%  is  proposed  for  authorised 
generic,  homeopathic,  herbal  medicinal  products  and  medicinal  products  authorised  on 
grounds of  well-established  medical use, for the same reasons as outlined for the flat fee in 
option  216.  However,  where  such  products  are  involved  in  the  EU  pharmacovigilance 
procedures, there would be no fee reduction and the normal procedure-based fee would apply.   

Option 4: Procedure based fees only, no flat fee 

All  costs  for  pharmacovigilance  activities  in  a  given  year  would  be  covered  on  average 
through fees charged only to those MAHs having, in that particular year, a medicinal product 
involved  in  one  of  the  procedures,  i.e.  (1)  the  assessment  of  PSURs,  (2)  the  assessment  of 
PASSs  and  (3)  the  assessment  in  case  of  pharmacovigilance  referrals.  The  non-procedure 
related costs of the EMA would be proportionally distributed among these three procedures, 
based on the workload involved within the procedures. 

A  fixed  overall  fee  amount  per  single  PSUR  procedure  would  be  based  on  its  estimated 
average  cost  including  the  proportion  of  non-procedure  related  costs,  totalling  to  €  33  794. 
The distribution of the fee among the MAHs would be based on the proportion of chargeable 
units  (e.g.  EV-codes)  related  to  the  MAHs  for  each  active  substance  (or  combination  of 
substances) that is subject to the PSUR procedure. 

16 Products which have been registered at national level under the procedure laid down in Chapters 2 and 2a of 
Directive 2001/83/EC are excluded from all fees. 

EN 

17 

   EN 

 
 
 
 
 
 
 
 
 
 
                                                 
A fixed overall fee amount per single PASS assessment would be based on its estimated costs 
including the proportion of non-procedure related costs, totalling to € 84 966. In the case of 
joint  studies,  this  amount  will  be  divided  by  the  number  of  marketing  authorisation  holders 
that have conducted the study. 

A  fixed  overall  fee  amount  per  pharmacovigilance  referral  would  be  based  on  its  estimated 
costs  including  the  proportion  of  non-procedure  related  costs,  totalling  to  €  332  136.  The 
distribution of the fee among the MAHs would be based on the number of MAHs taking into 
account the number of EV-codes they hold in relation to the product(s) in question.  

Reductions (fee incentives) for certain categories of  MAHs, such as SMEs,  would apply. A 
SME fee would be set at the level of 60 % of a full fee per procedure and no fee would be 
charged to the MAH which is a micro-enterprise. No other fee reductions or fee waivers are 
foreseen for marketing authorisation holders under this option. 

EN 

18 

   EN 

 
 
 
 
6.  ASSESSMENT OF IMPACT OF THE OPTIONS 
The  impact  of  each  option  is  considered  for  three  main  stakeholders  who  will  be  directly 
influenced, i.e. (1) the MAHs, (2) the National competent authorities (NCAs) of the MS (3) 
and the EMA and the European Commission. 

As indicated in chapter 4, the criteria for assessing the alternative fee systems stem directly 
from the operational objectives of the initiative, i.e. to establish the appropriate structure and 
the level of fees for pharmacovigilance. The criteria are defined as follows: 

Transparency – i.e. clear relationship between the type and level of fee and the corresponding 
work carried out.  

Fairness  -      i.e.  the  notion  that  the  MAH  should  contribute  to  the  financing  of 
pharmacovigilance activities  on the basis of potential safety concerns, recognising that not all 
products have the same safety profiles.  Avoiding cross-subsidisation and double charging as 
far as reasonably achievable is another dimension of the fairness principle.  

Stability -   i.e. the need to provide for a stable pharmacovigilance fee-system based on the 
highest  possible  degree  of  financial  predictability  and  avoiding  variable  remuneration  of 
similar scientific services.  

Simplicity – i.e. minimum additional administrative burden and complexity.  

As  regards  Member  States  and  their  scientific  involvement  as  rapporteurs  /  co-rapporteurs, 
these  activities  would  be  covered  through  remuneration  received  from  the  EMA  for  each 
assessment  procedure  in  which  the  rapporteurs  of  NCAs  would  participate.  The  level  of 
remuneration will be based on the average costs per type of procedure as estimated in Annex 
3. As in all options, the exact yearly amount that will be paid in remuneration of rapporteurs 
from  the  MS  cannot  be  predicted  with  a  100  %  accuracy,  given  that  the  exact  number  of 
procedures is unknown. It is however assumed that the total amount of € 10.5m intended to be 
collected from MAHs17 would be paid overall to MS in an average year.  

Since  a  cost-based  approach  has  been  chosen,  options  2  to  4  should  on  average  ensure 
adequate  funding  of  EMA's  pharmacovigilance  activities.  Option  1,  according  to  which  no 
legal proposal on pharmacovigilance fees would be adopted, would obviously not ensure this. 

Annex 4 outlines the calculations of the amount of the fees for each considered option. The 
calculations are based on the estimated costs of the pharmacovigilance activities presented in 
Annex 3. The results of the calculations as well as the main arguments in favour and against 
each option are outlined and analysed under sections 6.1 – 6.4 below. 

 Further information on impacts according to the criteria is summarised in Annex 7.   

17 See Annex 3 

EN 

19 

   EN 

 
 
 
 
 
 
 
 
 
 
                                                 
6.1.  Option 1: No change to the current situation  

In  general,  a  potential  lack  of  action  would  prevent  the  2010  pharmacovigilance  legislation 
from  being  fully  implemented  and    would  therefore  totally  undermine  the  public  health 
benefits deriving from the legislation, as analysed in the corresponding impact assessment of 
2008. The 2010 legislation explicitly foresees the introduction of fees for pharmacovigilance 
(see Annex 6).  

Impacts on marketing authorisation holders (MAH) 

The  marketing  authorisation  holders  would  not  benefit  from  the  enhanced  and  rationalised 
pharmacovigilance system introduced by the 2010 pharmacovigilance legislation. Moreover, 
MAHs would lack clarity as regards the sustainability and the funding of pharmacovigilance 
activities in the EU. 

Impacts on Member States 

As a consequence of the EMA not receiving adequate funding for the implementation of the 
pharmacovigilance activities as assigned to it by the 2010 pharmacovigilance legislation, the 
Member  States'  rapporteurs  and  co-rapporteurs  would,  in  turn,  not  be  remunerated  by  the 
EMA to cover their costs for their assessment work within the EU procedures. This would in 
turn reinforce the negative impact on the EMA, as it would become increasingly difficult to 
find rapporteurs for the individual procedures. 

Impacts on the EMA and European Commission 

In  this  scenario,  the  EMA  would  not  be  in  a  position  to  fully  implement  its  new  tasks  with 
regard  to  the  2010  pharmacovigilance  legislation  that  has  put  the  EMA  at  the  centre  of  the 
new  pharmacovigilance  system  in  the  EU.  This  would  be  due  to  the  absence  of  adequate 
funding for the costs incurred for the performance of these tasks. 

In such an event, the Commission's position would be perceived as a failure to act in view of 
its exclusive powers to put forward legislative proposals within the EU legislative framework. 
As  mentioned  above,    the  2010  pharmacovigilance  legislation  foresees  the  introduction  of 
fees. This would therefore also be perceived as a loss of credibility of the Commission. The 
financial statement that accompanied the legal proposal in 2008 foresaw that all costs relating 
to  pharmacovigilance  should  be  covered  through  fees.  Moreover,  the  public  health  benefits 
envisaged as a consequence of the pharmacovigilance legislation would not be achieved. 

6.2.  Option  2:  One  annual  flat  fee  covering  all  pharmacovigilance 

activities at EU level 

Impacts on marketing authorisation holders (MAH) 

In  this  scenario,  each  MAH,  with  the  exceptions  explained  in  Chapter  5,  would  be  charged 
once  per  year  for  all  pharmacovigilance  activities  performed  at  EU  level,  based  on  an 
'insurance' principle, rather than on an 'incident' principle. All products on the market would 

EN 

20 

   EN 

 
 
 
 
 
 
 
 
 
 
be considered as potentially subject to safety concerns at the same level and would contribute 
equally to the financing of the pharmacovigilance activities at EU level. Such a system would 
not be perceived as fair by all MAHs, especially those whose products have a well-established 
safety profile and would thus normally be less involved in the EU procedures. Moreover, the 
level of the fee would be perceived differently by the MAHs depending on whether they have 
had dealings with the EMA. The perception of the fee level by MAHs would also depend on 
their market power and the size of their product portfolio.  

A flat fee is a predictable fee that MAHs would be able to take account of in their financial 
planning. Also, MAHs would not be charged separately for any individual EU procedures, as 
all costs would have been covered through the flat fee. At the same time, flat fees are often 
considered less transparent compared to fees for well-defined, specific activities, where such a 
definition is possible. Thus, individual fees might be perceived by some industry stakeholders 
as  non-cost-based.  This  is  the  case  in  particular  for  MAHs  that  do  not  expect  any  (or  very 
little) involvement in the EU procedures. 

Also, MAH that are unlikely to be concerned by any of the EU procedures and those that have 
at present no contacts with EMA are likely to question the fee, particularly if they already pay 
pharmacovigilance fees to one or several NCAs.   

In comparison with options 3 and 4, option 2 is also less transparent and, therefore, the MAHs 
may perceive that they are charged twice for the same work by EMA and by NCAs.  

Impacts on Member States 

Rapporteurs and co-rapporteurs from MSs would cover their costs for their assessment work, 
through  remuneration  received  from  the  EMA  for  each  assessment  procedure  related  to 
pharmacovigilance  at  EU  level.  As  under  any  of  the  options  2-4,  rapporteurs  would  be 
remunerated according to a scale based on average costs and workload per type of evaluation 
procedure.  As  in  all  options  (save  option  1),  remuneration  would  take  place  whenever  the 
rapporteur is carrying out work within any of the EU procedures.  

Impacts on the EMA and the European Commission 

In this scenario, the EMA would charge to all MAH a single pharmacovigilance fee, for all 
authorised products, in accordance with structured information on medicinal products stored 
in  the  database  populated  in  the  context  of  Article  57(1)(l)  and  Article  57(2)  of  the 
Pharmacovigilance Regulation (Regulation  (EU)  No  1235/2010  of the European Parliament 
and of the Council of 15 December 2010 ).  

This means a stable, predictable revenue for the EMA. It is anticipated that the flat fee would 
be charged annually. The invoicing and collection of fees would be automated to the extent 
possible.    This  would  alleviate  the  administrative  work  and  the  number  of  transactions  and 
invoiced parties will be slightly lower than under option 3 but considerably higher compared 
with option 4.    

In  this  scenario,  the  collection  of  the  fee  would  be  disconnected  time-wise  from  the  actual 
pharmacovigilance  procedures.  The  EMA  would  therefore  have  to  ensure  sound  financial 
management of the pharmacovigilance fee revenue throughout the year, including earmarking 
funds for remuneration of MS rapporteurs, with underlying uncertainties regarding the actual 
occurrence and the timing of some EU procedures, i.e. pharmacovigilance referrals and PASS 
assessments. Therefore, this option may lead to a risk of insufficient funding for EMA should 
the number of procedures, notably referrals, increase substantially beyond what is expected. 

EN 

21 

   EN 

 
 
 
6.3.  Option  3:  A  combination  of  separate  fees  for  procedure  based 
activities and an annual flat fee for all other activities at EU level 

Impacts on marketing authorisation holders (MAH) 

In this scenario, MAHs would be charged as follows:  

•  all MAHs in the EU18  (with the exceptions explained in Chapter 5) would be charged 
an annual flat fee, as in option 2, but for a lower amount, depending on the number of 
products/authorisations in their portfolio; 

•  MAH having at least one product involved in a pharmacovigilance procedure  would 

be charged the corresponding procedure-based fee. 

The MAHs that are not involved in any EU procedure, would only pay the annual flat fee. As 
regards this fee fee, the same advantages and drawbacks apply as explained under option 2. 

In  terms  of  transparency,  fairness  and  proportionality,  the  procedure  based  fee  is  the  most 
service- / cost-oriented fee and scores better as compared to option 2. Despite the fact that the 
flat fee component is not fully cost-based on individual level, this option overall presents the 
most  detailed  fee  grid,  which  would  facilitate  comparison  with  national  fees.  This  option, 
therefore,  would  facilitate  the  adjustment  by  Member  States,  if  necessary,  of  their  national 
fees. 

Some  of  the  procedure-based  fees  (i.e.  PhV  referrals,  PASS)  would  be  less  predictable  for 
MAH compared to the flat fee because the actual occurrence and the scope of such procedures 
are not known in advance.  

Impacts on Member States 

As under the options 2 and 4, MS acting as rapporteurs would be remunerated according to a 
fixed scale based on average estimated costs per type of procedure. As for the other options, 
the  exact  yearly  amounts  that  would  be  paid  to  the  MS  is  not  predictable  given  that  the 
number  of  procedures  are  more  difficult  to  predict  (except  for  PSURs).  However, 
remuneration is linked to the actual work carried out.  

Under  this  option  the  fees  are,  therefore,  proportionate  to  the  workload  and  the  costs,  but 
cannot be entirely predictable by the inherent nature of the pharmacovigilance activities at EU 
level. 

Impacts on the EMA and the European Commission 

The fee revenue would overall cover the average costs of the EMA. The fee revenue is thus 
proportionate  to  its  workload.  For  the  annual  flat  fee,  the  same  advantages  and  drawbacks 
apply  as  indicated  under  option  2  above.  However,  in  comparison  with  option  2,  the  actual 
level of the annual flat fee would be considerably lower (as cost of procedures would not be 
included  in  the  calculation  of  that  fee).  The  administrative  work  for  EMA  would  be  higher 
compared to option 2. This is because contrary to the annual flat fee component, the invoicing 
of  the  procedure-based  fee  component  cannot  be  fully  automated.  Moreover,  the  number  of 

18 as per information registered by the EMA in the database set up by Art 57 of the Regulation 

EN 

22 

   EN 

 
 
 
 
                                                 
invoiced parties will be higher but this will largely depend on the number of EU procedures 
and the number of MAHs and products involved in the procedures.   

This option would ensure the funding of the procedure-related activities in a timely manner.  

The  EMA  would  have  to  apply  the  fee  reductions  for  authorised  generics,  homeopathic, 
herbal and medicinal products authorised under well-established use in respect of the annual 
flat fee component. 

The additional number of invoiced parties may be estimated as follows: 

•  3.275 additional invoiced parties for the procedure-based activities, i.e.: 

o  for PSUR assessments: (approximately 600  per year), 1.800 additional invoiced 

o 

parties with amounts itemized per MAH  
 for PASS assessments (approximately 35  per year), 35 additional invoiced 
parties (if several MAHs conduct the study jointly, they may share the fee 
amongst themselves) 

o  for pharmacovigilance referrals (approximately 40  per year), 1.440 additional 

invoiced parties19  

6.4.  Option 4: Only procedure-based fees 

Impacts on marketing authorisation holders (MAH) 

In  this  option,  the  ‘insurance’  principle  would  be  completely  eliminated  in  favour  of  an 
approach  that  is  entirely  based  on  an  ‘incident’  principle.  Only  MAHs  whose  product(s)  is 
(are) concerned by a pharmacovigilance procedure would be charged a fee at the time when 
the procedure is launched. The fee levels per procedure would be higher than the procedural 
fee-levels in option 3 where procedure-based fees are combined with an annual flat fee. 

The  same  advantages  and  drawbacks  apply  as  explained  under  option  3  with  respect  to  the 
procedural fee component, with the difference that under this option, the general EMA costs 
(i.e. those which are not linked to any procedures) would be distributed only amongst those 
MAHs that are included in the procedures. If there is a proportionate distribution of the non-
procedure related costs in a transparent way this approach might be acceptable for the MAHs. 
On  the  other  hand,  those  MAHs  that  are  not  subject  to  any  EU  procedures  would  not 
contribute to the financing of the system whilst indirectly and potentially (i.e. should they be 
subject to EU procedures in the future) benefiting from it. In this respect, option 4 is likely to 
be less transparent, and less fair and proportionate than option 3. 

Impacts on Member States 

As  under  options  2  and  3,  MS  would  be  remunerated  according  to  a  fixed  scale  based  on 
average estimated costs for each type of procedure. However, the exact yearly amounts that 
would  be  paid  to  the  MS  are  not  predictable  given  that  the  number  of  procedures  is  more 
difficult to predict (except for PSURs). Remuneration is  linked to the actual work carried out.  

19 The EMA's forecast is an average number of 36 MAHs involved in a pharmacovigilance referral 

EN 

23 

   EN 

 
 
 
 
 
 
                                                 
Impacts on the EMA and European Commission 

As opposed to option 2 (a single pharmacovigilance fee) and option 3 (with respect to the flat 
fee component), the EMA would only charge a fee when an EU procedure is launched. 

The same advantages and drawbacks apply as explained under option 3 with respect to the 
procedural fee component. As regards the administrative work, the main difference is that the 
number of transactions and invoiced parties is significantly lower compared to both options 2 
and 3. Also, there is no need for EMA to apply any fee reductions for authorised generics, 
homeopathic, herbal and medicinal products authorised under well-established use (which 
they would do in respect of the flat-fee component under option 3). The regularity of PSUR 
assessments (as opposed to the other procedures which are less predictable) would have a 
positive effect on the funding of non-procedure related activities of EMA.  

Under  this  option,  the  fees  are  proportionate  to  the  workload  and  the  costs,  but  cannot  be 
predictable due to the inherent nature of the pharmacovigilance activities at EU level. 

6.5. 

Comparison of the options 

The  criteria  for  evaluating  the  options  follow  the  principles  of  effectiveness,  efficiency  and 
coherence. As already explained, the specific criteria against which the options are compared 
include  (1)  transparency  of  the  fee  levels  and  structure,  (2)  stability  and  financial 
predictability  of  fees,  (3)  the  simplicity  of  the  fee  structure  and  (4)  fairness  and 
proportionality of fees.  

Table 2 below summarises the analysis of individual options from chapters 6.1-6.4 and Annex 
7 and assigns the scores of how well each option meets the criteria as compared to baseline 
scenario. The  assessment of  the way the different options meet the four criteria /  objectives 
has  been  performed  by  attributing  scores  as  per  a  scale  from  1  to  3.  Scores  are  relative 
compared to the baseline scenario and are defined as follows:  

1  
2  
3 

Slightly more positive effect as regards meeting the criterion / objective 
More positive effect as regards meeting the criterion / objective 
Very much more positive effect as regards meeting the criterion / objective 

Table 2: Comparison of options and how they meet objectives relative to baseline 

Options  /  Objectives 

transparency 

stability / 
predictability 

simplicity 

fairness / 
proportionality 

1. Baseline 
2. Flat Fee 
3. Combination of an 
annual flat fee and 
procedure-based fees 
4. Procedure-based fees 
only 

0 
1 

3 

2 

EN 

0 
3 

1 

2 

0 
1 

3 

2 

0 
3 

2 

1 

24 

   EN 

 
 
 
 
 
 
 
 
Analytical hierarchy process technique was used in order to assign weights to each criterion to 
reflect  and  formalize  its  relative  importance.  The  individual  steps  of  that  analysis  are 
described in  detail  in Annex  9. The results suggest the following relative weights: 45 % on 
fairness and proportionality, 32 % on transparency, 14 % on stability and predictability and 9 
% on simplicity. This hierarchy of relative importance of all four criteria was applied to the 
analysis of individual options summarised in Table 2 above. The result of this final step of the 
comparison  between  the  options  is  outlined  in  Table  5.  The  final  absolute  scores  determine 
the ranking of the options in terms of achieving objectives. 

Table 5: Final comparison of options 

Options  /  Objectives 

transparency 

stability / 
predictability 

simplicity 

fairness / 
proportionality 

Total     
Score 

Option 1 
Option 2 
Option 3 
Option 4 

0 
3 

10 

6 

0 
4 

3 

1 

0 
3 

1 

2 

0 
5 

14 

9 

0 
15 

27 

19 

Based on that analysis, option 3, i.e. the combination of procedure-based fees and an annual 
flat fee, is the preferred option. 

A combination of procedure-based fees and an annual flat fee has been considered to be the 
most transparent, cost-based, activity-based and proportionate way of setting the new fees, in 
order  to  cover  the  EMA’s  costs.  In  this  way,  the  medicinal  products  being  part  of  a 
pharmacovigilance  procedure  at  EU  level  will  contribute  to  the  financing  of  the  cost  of  the 
procedure. At the same time, the costs of general pharmacovigilance activities of the EMA, 
and  only  that  part  of  the  cost,  would  be  covered  through  an  annual  flat  fee  charged  for  all 
authorised products in the EU, which benefit from the EU pharmacovigilance system.  

7.  MONITORING AND EVALUATION 
The  monitoring  will  be  linked  to  the  implementation  of  annual  budget  of  the  EMA.  The 
annual activity report on the performance of the EMA will provide reliable information and 
key indicators such as  

•  Number of EMA staff involved in pharmacovigilance activities as per the legislation 

applicable during the reference period. 

•  Number  of  hours  outsourced  to  third  parties  with  specification  of  the  activities 

concerned. 

•  Overall  pharmacovigilance  costs  and  a  breakdown  of  costs  relating  to  each  of  the 
procedures referred to in Articles 4-6 of this Regulation as well as the costs relating to 
the activities referred to in Article 7 of this Regulation. 

•  Number  of  procedures  relating  to  the  single  assessment  of  periodic  safety  update 

EN 

25 

   EN 

 
 
 
 
 
 
reports,  as  well  as  number  of  marketing  authorisation  holders  and  number  of 
chargeable  units  per  procedure;  number  of  reports  submitted  per  procedure  and 
number of marketing authorisation holders that have submitted a joint periodic safety 
study report. 

•  Number of procedures relating to the assessment of post-authorisation safety studies; 
number of marketing authorisation holders having carried out such studies and number 
of marketing authorisation holders that have submitted a joint study. 

•  Number  of  procedures  relating 

the  basis  of 
pharmacovigilance  data  as  well  as  number  of  marketing  authorisation  holders  and 
number  of  chargeable  units  involved  per  marketing  authorisation  holder  and  per 
procedure. 

the  referrals 

initiated  on 

to 

•  Number  of  marketing  authorisation  holders  that  have  claimed  a  small  and  medium-
sized enterprise status involved in each procedure; number of marketing authorisation 
holders whose claim has been denied. 

•  Number  of  marketing  authorisation  holders  that  have  claimed  a  micro  enterprise 
status; number of marketing authorisation holders whose claim for fee exemption has 
been denied.  

•  Number of marketing authorisation holders of medicinal products referred to in Article 
10(1) of Article 10a of Directive 2001/83/EC that have benefitted from reduced annual 
flat fees; number of chargeable units per marketing authorisation holders concerned.  

•  Number of invoices sent out in respect of the annual flat fee and average and overall 

amount invoiced to marketing authorisation holders.  

•  Number  of  marketing  authorisation  holders  that  have  claimed  a  small  and  medium-
sized enterprise or a micro enterprise status for each annual application of the annual 
flat fee; number of marketing authorisation holders whose claim has been denied. 

These indicators will allow assessing the sustainability of EMA financial resources in the area 
of  pharmacovigilance  over  a  period  of  time.  The  overall  effectiveness  and  efficiency  of  the 
pharmacovigilance  services  offered  to  industry  by  the  EMA  including  work  of  rapporteur 
NCAs will be measured by the EMA using indicators such as timeliness and quantity of the 
services provided.  

All  this  should  be  sufficient  to  ensure  an  effective  monitoring  of  the  functioning  of  the 
proposed action. On the basis of the data submitted by EMA, the Commission will consider 
whether there is a need to revise the level of the fees.  

EN 

26 

   EN 

 
 
 
 
ANNEX 1 - LIST OF ABBREVIATIONS 

ADR:  

Adverse Drug Reaction 

Article 57(2) database  A database based on the list of all medicinal products for human use 
authorised in the EU which is set up and maintained by the EMA in 
accordance  with  Article  57(1)(l)  and  Article  57(2)  of  Directive 
2001/83/EC. 
Centrally Authorised Product 

CAP:  

CMDh:  

CHMP: 

Coordination Group for Human Medicinal Products 

Committee for Medicinal Products for Human Use 

Chargeable unit 

Unit used for the charging of the annual flat fee and for dividing the 

EMA:  

EURD list 

EV:  

EV-code: 

fees per procedure among MAHs. 

European Medicines Agency 

European  Union  Reference  Data 
active 
substances/combination  of  substances  with  dates  and  frequency  for 
submission  to  EMA  of  PSURs  for  substances  that  are  authorised  in 
more than one MS) 

(list 

list 

of 

The EURD list, which became applicable in April 2013, is intended to 
optimise the management of PSURs assessment within the EU while 
supporting  transparency.  It  aims  to  provide  predictability  to  the 
various  stakeholders  in  terms  of  workload  related  to  PSURs,  taking 
into  account  the  currently  known  safety  profile  of  the  active 
substances  and  combinations  of  active  substances.  The  knowledge 
about  the  safety  profile  has  been  considered  when  determining  the 
frequency of the submission of PSURs, i.e. for substances with well-
known  safety  profiles  that  have  been  on  the  market  for  a  longer 
period,  PSURs  will  be  required  less  frequently  compared  to  newer 
substances. 

EudraVigilance database (of ADRs) 

An individual entry in the Article 57(2) database intended to describe 
with maximum precision a medicinal product in the EU, taking into 
account the different ways in the EU of assigning authorisation 
numbers to and counting medicinal products. The medicinal product is 
described as sold or supplied to a consumer or patient.  This is a 
harmonised way of registering medicinal products authorised 
throughout the EU, according to methodology developed by the EMA, 
in accordance with ISO standards of product definition. EV code is 
the most harmonised common denominator used across the EU. 

FTE: 
MA:  
MAH:  

Full Time Equivalent 
Marketing Authorisation 
Marketing Authorisation Holder 

EN 

27 

   EN 

 
 
 
 
 
MRP / DP:  
MS:  
NAP:  
NCA:  
PASS:  
PRAC:  
PSUR:  

Mutual Recognition Procedure / Decentralised Procedure 
Member State 
Nationally Authorised Product (including MRP/DP) 
National Competent Authority 
Post-Authorisation Safety Study 
Pharmacovigilance Risk Assessment Committee 
Periodic Safety Update Report 

EN 

28 

   EN 

 
ANNEX 2 – SUMMARY OF THE PUBLIC CONSULTATION 

On 18 June 2012 the European Commission published a Concept Paper20 on the introduction 
of  fees  to  be  charged  by  the  European  Medicines  Agency  for  pharmacovigilance.  The 
consultation period ended on 15 September 2012. 

The Commission received 85 replies (9 requesting confidentiality): 

•  66 from industry, associations and individual companies 

o 

including 30 from SMEs 

•  12 from national competent authorities (NCA), 

o  AT, DE, DK, EL, ES, IRL, MT, NL, NO, SE, and UK 

o  HMA,  

•  4 from civil societies and other associations, 

•  3 from individual persons. 

This document summarises the responses to the public consultation on the concept paper. It is 
in  no  way  to  be  understood  as  an  endorsement  of  any  comment.  For  the  sake  of  brevity, 
consultation items are not reproduced. Therefore, this summary should be read in conjunction 
with the consultation items set out in the concept paper. 

The public consultation is part of the on-going impact assessment exercise. The information 
and views gathered in this public consultation will be taken into consideration in the impact 
assessment process. 

GENERAL REMARKS 

The  public  consultation  was  appreciated  by  stakeholders.  However,  the  vast  majority  of 
respondents did not support or fully support the proposed fees, notably as regards the amounts 
proposed.  There  was  generally  a  view  that  the  concept  paper  did  not  present  sufficient 
information  about  the  basis  for  the  estimations  (in  terms  of  workload  and  costs)  of  the 
proposed fees.  

Many  respondents  question  the  benchmarks  that  have  been  used  and  consider  as  a  more 
appropriate approach the time used and the associated costs for the work. The majority of the 
respondents consider the proposed fees as being too high and without sufficient justification 
and transparency.  
The  vast  majority  of  the  respondents  made  reference  to  the  financial  statement  of  200821 
questioning  the  significant  increase  in  the  proposed  fee  levels  compared  with  this  financial 
statement  and  the  lack  of  sufficient  explanation  or  justification  for  such  an  increase.  It  is 
argued that the amendments made to the initial legal proposal during the legislative process 
were  not  of  such  type  or  magnitude  to  justify  such  a  sharp  increase  in  the  amount  of  fees. 

20 http://ec.europa.eu/health/files/pharmacovigilance/2012-06_concept_paper_en.pdf 
21 http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=COM:2008:0664:FIN:en:PDF 

EN 

29 

   EN 

 
 
 
                                                 
Also, some argue that the fees in the financial statement of 2008 are more closely aligned with 
those of the NCAs which charge separately for pharmacovigilance activities.  

Many respondents from industry argue that the proposed fees are contrary to the objective of 
the  legislation  to  reduce  the  costs  and  the  unnecessary  administrative  burden  for  the 
pharmaceutical  industry.  Some  have  estimated  that  the  proposed  fees  would  lead  to  an 
increase by more than 50% of their budget for fees and, for some pharmaceutical companies, 
even double this budget. The need for transparency is emphasised, as well as the importance 
that  marketing  authorisation  holders  are  not  charged  twice  for  the  same  assessment  work. 
Industry, in particular, flags the risk of possible duplicative fees charged by EMA and NCAs 
and expects a reduction of national fees whenever work is shifted to the EMA. 

The  Concept  Paper  has  put  forward  the  possibility  of  grouping  of  MAHs  for  many  of  the 
proposed  fee  types  (for  the  purposes  of  paying  one  single  fee),  as  a  result  of  which  MAHs 
would  in  many  cases  not  need  to  pay  the  maximum  or  full  fee.  However,  the  grouping  to 
share  the  fee  for  PSUR  and  PASS  assessments  was  not  supported  by  the  vast  majority  of 
respondents who argued that this would not work in practice as it would require the sharing of 
confidential  information  between  MAHs  not  belonging  to  the  same  legal  entity  (see  2.3. 
Concept  of  grouping  applied  to  PSURs,  PASSes  and  Pharmacovigilance  Referrals 
[Consultation items 2, 4 and 6]). 

Many  respondents  consider  that  proposed  fees  would  unfairly  affect  MAHs  with  a  large 
portfolio  of  products  with  well-established  safety  profiles  and  many  MAs.  Such  comments 
come  mainly  from  industry  stakeholders  representing  generics,  homeopathics,  well-
established-use and over-the-counter medicinal products, including allergen manufacturers.  

Almost  all  SMEs  express  concern  about  the  proposed  fee  levels,  stating  that  even  with  the 
proposed fee reductions, the availability of their products would be under threat. 

Many NCAs express criticism that the concept paper lacks information about the distribution 
of  fees  to  the  NCAs  acting  as  rapporteurs  and  co-rapporteurs  during  the  assessment 
procedures. On this point, especially industry advocates an analysis of the actual tasks carried 
out by the EMA secretariat and the NCAs in each instance.  

There  are  also  calls  for  further  clarity  on  how  the  proposed  fees  have  been  established  and 
questions on whether the benchmarks correspond to the scope and volume of documents to be 
reviewed,  activities  to  be  undertaken  and  number  of  staff  involved;  they  call  for 
proportionality  between  the  fees  and  the  nature  of  the  work  actually  carried  out.  Some 
respondents  acknowledge  the  difficulty  of  having  a  fee  adjusted  to  each  individual 
procedure/product, and rather advocate setting up a single fee or a simple range of fees based 
on  well-defined  and  justified  criteria  for  each  procedure  corresponding  to  the  associated 
workload. 

A  number  of  respondents,  especially  from  industry,  consider  that  some  pharmacovigilance 
activities, e.g. referrals and literature monitoring, should be at least partly covered by the EU 
budget as these activities are linked to the protection of public health.  

EN 

30 

   EN 

 
SUMMARY OF COMMENTS 

Fee for assessments of Periodic Safety Update Reports (PSUR)  

In general, the principle of charging a fee for the assessment of a PSUR has not been objected 
to,  except  when  there  is  a  risk  of  a  possible  double  charging  for  essentially  the  same  work 
(e.g.  when  a  PSUR  submission  would  coincide  with  a  renewal  assessment).  However,  the 
proposed  levels  of  the  fee,  benchmarked  against  a  Type  II  Variation  procedure,  have  been 
criticised, mainly by industry, but also by some National Competent Authorities.  

The  main  criticism  to  the  proposed  fee  stems  from  the  feeling  that  benchmarking  against  a 
Type II Variation is not fully justified, in order to reflect the real workload associated with the 
assessment  of  PSURs.  Some  replies  from  industry  suggest  that  the  workload  of  a  PSUR 
assessment  is  lower  than  a  type  II  Variation,  whereas  others  from  NCAs  suggest  that  the 
workload could be higher. 

Some respondents refer to the need for more precise and transparent cost calculations in order 
to  arrive  at  the  cost  of  an  ‘average’  assessment.  Others  would  prefer  a  greater  number  of 
levels of fees, based on criteria related to the assessment effort, e.g. the number of ADRs or 
literature cases (or a reduction for products whose safety profile is well established). 

It is also pointed out that the expected number of PSUR assessments should be estimated in 
relation to the possible effect on the budget of the EMA.  

The  relevance  of  using  the  two-year  period  following  the  authorisation  as  a  method  of 
approximation  of  the  assessment  workload  (and  the  related  fee)  is  questioned,  notably  for 
products where the benefit/risk profile has been well established.  In this respect, comments 
both from industry and NCAs point out that the frequency of PSUR submission, as defined by 
the  EU  reference  date  list,  could  be  taken  into  account.  Many  comments  argue  that  the 
workload  in  the  first  two  years  could  actually  be  higher  than  afterwards.  It  is  however 
generally recognised that the administrative complexity of the pharmacovigilance fee system 
should be minimal.  

Some respondents point out that the ‘cascade effect’ on overall amounts charged to industry 
for  subsequent  procedures  should  be  taken  into  account  (e.g.  a  PSUR  leading  to  a  referral 
leading to a variation). 

As  an  alternative  benchmark,  the  existing  renewal  fee  for  a  centrally  authorised  product  is 
often proposed, because considered to require similar workload. Possible duplication of PSUR 
assessment  and  renewal  assessment  for  newer  products  is  signalled  in  this  repect. 
Alternatively,  national  fee  levels  are  quoted  as  a  potential  benchmark,  namely  fees  paid  by 
industry for MRP and DCP products. 

Also, as non-CAPs are subject to subsequent national variation fees, concerns are expressed 
over a possible violation of the principle of equal treatment (of CAPs and non-CAPs). 

Fee for assessments of Post Authorisation Safety Studies (PASS)  

Overall, the benchmark (Type II Variation) has been questioned and it is argued that the data 
to be assessed is not comparable, in that a PASS assessment concerns a single report whereas 
a Type II variation may include several studies and may be more complex, as it may require a 
revision  of  several  sections  of  the  product  information.  Where  the  PASS  results  lead  to  an 
update  of  the  MA  of  a  non-CAP  through  a  variation,  for  which  fees  are  normally  charged, 
there is concern that MAHs would be charged two separate fees for these activities which are 
related. 

EN 

31 

   EN 

 
 
It is proposed that the fee for PASSes should be based on several criteria, such as the methods 
used for the PASS and the amount and type of data collected; however, to avoid complexity, 
comments  suggest  setting  a  fee  or  a  simple  fee  range  closer  to  the  PASS  assessment  fee 
included in the financial statement of 2008.  

Especially some respondents from industry express concerns about the discrepancy where no 
separate variation (and, consequently, no variation fee) will be required in the case of PASS 
leading to a change in the MA for CAPs, whereas for non-CAPs, a subsequent variation will 
still be required and charged for.  

Concept of grouping applied to PSURs, PASSes and Pharmacovigilance Referrals  

While a number of respondents support the concept in general, as a means to reduce the actual 
amounts  to  be  paid,  most  of  the  comments  refer  to  the  need  to  clarify  whether  MAHs 
belonging to the same mother company or group of companies (and MAHs having concluded 
agreements  or  exercising  concerted  practices  concerning  the  placing  on  the  market  of  the 
medicinal  product(s)  concerned),  should  to  be  taken  as  ‘the  same  marketing  authorisation 
holder’  (as  per  Commission  Communication  OJ  C  229,  22  July1998).  They  argue  that  they 
should  be  considered  as  a  single  legal  entity  and  that  this  should  not  be  considered  as 
grouping.  In  addition,  comments  state  they  should  not  be  charged  additional  administrative 
fees.  

Grouping for submitting PSURs is generally considered very difficult in practice (sharing of 
commercial data, different standard operating procedures, difficulty to divide the work and to 
coordinate  between  different  QPPVs,  ...),  except  for  entities  belonging  to  the  same  mother 
company.  In  this  respect,  it  is  pointed  out  that  producing  a  single  PSUR  with  all  the 
information,  data  and  analysis  coming  from  independent  companies  seems  unrealistic. 
Consequently, comments from industry express concern that the anticipated savings through 
grouping would not materialise in practice.  

Some respondents consider grouping for PASSes as an option but draw the attention to some 
practical/legal  constraints.  While  grouping  for  the  PASSes  may  facilitate  the  collaboration 
between independent MAHs to conduct PASS jointly (as foreseen in the pharmacovigilance 
legislation), it would require a model-based system for the fee assignment that complies with 
the principles of proportionality, equal treatment of MAHs and with competition laws. Where 
PASSes  are  conducted  jointly  by  different  MAHs,  it  is  proposed  that  the  total  PASS  fee 
(including  any  administrative  fees)  is  equally  divided  amongst  all  concerned  MAHs  for  the 
same PASS.  

The  concept  of  grouping  is  considered  more  relevant  in  the  case  of  referrals,  (where  it  is 
already  now  possible  to  pay  one  single  referral  fee),  but  several  respondents,  notably  the 
generics industry, request clarification about how the fee would be divided. 

Several  respondents  consider  the  administrative  fee  of  500€  as  being  too  high.  Most  NCAs 
consider that the administrative fee should not be retained in full by the EMA. 

In  some  replies  it  is  pointed  out  that  the  concept  of  grouping  is  not  applicable  for  some 
specific products, e.g. for allergen extracts. 

EN 

32 

   EN 

 
 
 
 
 
 
Pharmacovigilance referrals  

The  benchmark  used,  i.e.  assessment  of  initial  MA  application,  is  heavily  criticised.  The 
proposed  fee  for  pharmacovigilance  referrals  involving  full  benefit-risk  assessment  is 
considered by many as too high and the work is not considered to be comparable to assessing 
an  initial  marketing  authorisation  application.  This  is  especially  underlined  by  the  generics 
industry. Also, it is pointed out that the assessment of an initial MA is much broader including 
also  non-clinical  data  and  data  on  chemistry,  manufacturing  and  controls,  whereas  in  the 
referral, the focus is on the new information that triggered the referral. Recognising that the 
workload for each referral will vary, some respondents express preference to have one single 
fee.  In  any  event,  there  is  a  general  call  for  better  explanation  and  justification  of  the 
workload involved. 

Many respondents from the generic industry argue that they are more likely to be subject to 
several  referrals  due  to  their  broad  portfolio  compared  to  innovator  companies,  which  is 
claimed to be disproportionate considering the comparative turnovers. 

Some  respondents  suggest  a  fee  reduction  for  referrals  initiated  by  PRAC  within  the  same 
class of medicinal products (referring to the same ATC code).  

Others consider that if a referral fee will be charged, the amount should be within the range of 
what is already in place for referrals initiated by MAHs.  

Also,  some  respondents  point  out  that  the  fact  that  in  addition  a  Type  II  variation  may  be 
requested, which is also subject to a fee, should also be considered in the referral fee. 

As regards payments to the PRAC rapporteurs and co-rapporteurs for their assessments, some 
respondents refer to the appointment principles laid down in EMA document of 28 June 2012 
whereby  the  co-rapporteurship  is  automatically  granted  to  the  Member  State  triggering  the 
referrals  involving  non-CAPs  or  CAPs/non-CAPs.  In  view  of  this,  attention  is  drawn  to  the 
risk that referrals could be initiated as a revenue generating exercise, rather than in response 
to a genuine safety concern. 

Some respondents consider that the referrals should be supported at least partly through the 
EU contribution to EMA. 

Pharmacovigilance service fee  

Some respondents, notably those representing the larger companies in the innovative sector, 
argue  that  the  concept  of  an  annual  fee  might  be  acceptable  for  certain  well-specified 
pharmacovigilance activities which constitute a service to the MAHs. However, there is call 
for  more  transparency  in  respect  of  the  tasks  which  are  covered  by  an  annual 
pharmacovigilance  service  fee.  The  fee  should  also  be  proportionate  to  the  costs  of  these 
activities. At the same time, many respondents from the industry point to the risk of double-
charging, as many NCAs already charge annual fees for pharmacovigilance. 

Particular concern is expressed by the generic industry, as many of its companies may have a 
large  portfolio  (e.g.  around  1000  active  substances)  which  would  lead  to  extremely  high 
charges for the proposed pharmacovigilance service fee alone. Similar concerns are expressed 
by other companies having products with a well-known safety profile which does not change 
much and generating very few ADR reports) and for companies with low-volume/low sales. 
They consider that MAHs belonging to the same group of companies (as one legal entity) and 
acting  under  one  pharmacovigilance  system  master  file  should  only  be  required  to  pay  one 
annual  fee  per  active  substance.  Some  representatives  of  the  generic  industry  argue  for  a 

EN 

33 

   EN 

 
 
reduced fee for generics, as they would not generate the same amount of work as innovator 
products. 

Several  respondents  consider  that  the  proposed  fee  unduly  favours  MAHs  with  only  one 
medicinal product with several strengths in several Member States, as opposed to MAHs with 
a  broad  product  portfolio  with  different  active  substances  but  only  marketed  in  a  small 
number  of  Member  States.  Some  SMEs  note  that  if  such  a  fee  is  charged,  it  should  be  per 
substance  and  MAH,  without  adding  charges  for  additional  strengths,  formulations  or  pack 
sizes. 

However, concern is expressed that annual fees are already charged by most Member States 
for non-CAPs and that there is a risk of multiple charging, if an annual fee is also charged by 
EMA for the same activities (charging twice for the same work). Assurances are being sought 
by  the  industry  that  the  Member  States  will  not  charge  such  a  fee  if  EMA  introduces  an 
annual pharmacovigilance service fee. 

Some NCAs are questioning the proposed pharmacovigilance service fee. Assuming that there 
are  some  3,500  active  substances  in  the  EU  in  addition  to  a  number  of  combinations  of 
substances, it is unknown how many MAHs per substance/combination of substances would 
have  to  pay  the  fee.  It  is  claimed  that  it  is  therefore  not  possible  to  assess  if  the  fee  is 
excessive  or  appropriate.  While  several  NCAs  express  support  for  an  annual  fee,  they 
consider  that  the  proposed  annual  pharmacovigilance  service  fee  level  is  disproportionally 
high. They also request clarification about what proportion of the fee would be transmitted to 
the NCAs for the work they carry out. 

In  addition,  some  respondents  point  out  that  CAPs  are  currently  paying  an  annual  fee  of 
which  30%  (ca.  28.770  €)  is  fore seen  for  pharmacovigilance  and  inspection  costs.  As  it  is 
proposed to continue to charge this fee, it is argued that there should be an analysis of the use 
of the revenue from this fee to ensure that a new annual fee would cover only new activities, 
which are not covered by the current annual fee.  

Many respondents argue that these general pharmacovigilance activities should be at least co-
financed by the EU and the Member States. 

Some civil society organisations express their disagreement with the proposed service fee as 
the  general  activities  that  are  proposed  to  be  covered  by  this  fee  do  not  include  support  to 
PRAC  members  (financial  compensation  for  their  participation).  They  consider  that 
pharmacovigilance  fees  could  also  be  used  to  cover  the  costs  of  measures  that  NCAs  and 
patients  and  healthcare  professionals'  organisation  are  taking  to  encourage  patients  and 
healthcare professionals to report suspected ADRs. To cover the costs for these activities, they 
propose to increase the proposed service fee to 1.250€, to be partially redistributed to NCAs, 
or to increase the current annual fee proportionally. 

ICT tools and services 

Some  of  the  respondents  support  the  concept  that  MAHs  should  contribute  to  the  general 
maintenance  of  EudraVigilance  and  the  PSUR  repository.  Many  industry  respondents  point 
out,  however,  that  they  have  already  had  to  invest  heavily  in  ICT  tools  and  databases  to 
comply  with  the  new  pharmacovigilance  requirements,  thus  questioning  the  need  to  include 
ICT  services  in  the  annual  fee.  Also  the  submission  of  information  (and  maintaining  the 
information  up  to  date)  on  medicinal  products  by  the  MAHs  to  the  Article  57(2)  database 
reportedly entails a heavy workload with considerable costs and it is not perceived acceptable 
to be charged a fee in this context. 

EN 

34 

   EN 

 
 
Many  manufacturers  of  non-prescription  medicines  argue  against  the  annual  service  fee  as 
they consider that companies, which have products with a well-established safety profile and 
few  ADR  reports,  will  hardly  benefit  from  the  signal  detection  of  EMA  on  the  basis  of 
EudraVigilance data.  

Literature monitoring 

Several industry respondents emphasize that they are already required to carry out literature 
monitoring of their products and that they will not be relieved from this responsibility, despite 
the  fact  that  EMA  will  monitor  certain  substances  in  selected  literature.  Therefore,  the 
charging of a fee for this activity is highly questioned as it cannot be regarded as a service to 
the industry. Moreover, as the EMA literature monitoring will not benefit all companies and 
products,  some  respondents  argue  that  it  would  be  unfair  to  charge  all  companies  for  this 
activity.  

Many respondents also argue that the same is true for signal detection in that the MAHs will 
continue to bear the responsibility for signal detection and evaluation for their products. 

Fee incentives for SMEs  

In general, the proposal for fee reductions for SMEs and full exemption for microenterprises 
is welcomed. 

Some industry representatives argue that, in addition to the proposed reduced fees for SMEs, 
there  should  also  be  reductions  for  orphan  medicinal  products  as  well  as  for  other  low 
volume/low sales products (to avoid that they may be withdrawn from the market due to the 
additional pharmacovigilance costs). 
Some suggest using a similar methodology as for the MedDRA22 subscriptions, whereby the 
companies are charged on the basis of their turnover. 

Several respondents request clarification on how SMEs with non-CAPs should apply for SME 
status at EMA in case a reduced annual fee for SMEs is charged. 

Some SMEs consider that further distinction should be introduced between the different types 
of  SMEs,  e.g.  suggesting  that  medium-sized  SMEs  be  granted  50%  reductions  and  small 
SMEs 75%. 

Many  respondents,  particularly  from  the  generic  industry,  point  out  that  the  number  of 
substances or combination of substances of a MAH is not necessarily related to the size of the 
company, especially when comparing the innovative and generic industry. 

Most NCAs argue that they should receive the non-reduced share  of the fee, irrespective of 
the reduction granted to SMEs (or any other reduction). 

Other comments  

Whilst the 2008 estimations accompanying the legislative proposal are currently outdated, and 
recognising that the final adopted legislation is not identical to the 2008 proposal, a number of 
respondents consider that the proposed new amounts should not be completely out of proportion 
with the 2008 figures. 

22 Medical Dictionary for Regulatory Activities - internatonal medical terminology used to classify adverse event information  

EN 

35 

   EN 

 
 
 
 
                                                 
There  are  requests  for  information  about  the  anticipated  revenues  for  EMA,  based  on  the 
proposed  fees,  and  how  this  links  with  their  costs,  in  order  to  be  able  to  assess  whether  the 
proposed fees are reasonable.  

Respondents  expect  a  fair  treatment:  e.g.  an  increase  in  companies'  fees  budgets  which  is  in 
proportion with their size; or taking into account the specificity of some products that generate 
very limited revenues, as argued for instance in the case of diagnostic products or products with 
a very limited availability. 

Whilst the 2008 Financial Statement and Impact Assessment indicated that all costs associated 
with  activities  from  the  proposal  should  be  recouped  through  fees,  a  number  of  respondents, 
mainly  from  industry,  argue  that  pharmacovigilance  activities  should  be  partially  publicly 
funded. Also, they expect an analysis of the possible effect on EMA's budget. 

Most  NCAs  (national  competent  authorities)  underline  the  importance  of  introducing  a 
transparent method for distribution of the fees between the EMA and the NCAs. A significant 
number  of  NCAs  state  that  NCA's  share  should  not  be  affected  by  any  reduction  of  the  fee. 
Many  NCAs  request  a  separate  pharmacovigilance  inspection  fee,  in  order  to  pay  directly  the 
inspectors  from  the  NCAs  that  have  participated  in  the  inspection.  Another  suggestion  is  to 
introduce  fees  for  (assessing  amendments  to)  risk  management  plans  ('RMPs'),  as  PRAC  will 
also be involved. 

Some  respondents  also  call  for  an  independent  arbitration  service  where  there  are  disputes 
concerning the fees. 

Some organisations representing civil society call for redistribution of pharmacovigilance fees 
to  NCAs,  which  could  give  grants  to  civil  society  organisations  for  their  participation  in 
pharmacovigilance  activities,  and  to  use  pharmacovigilance  fees  to  support  financially  civil 
society PRAC members. 

In  addition,  there  are  suggestions  to  charge  fees  to  cover  the  development  of  guidelines  and 
organising public hearings. 

EN 

36 

   EN 

 
ANNEX  3  –  PHARMACOVIGILANCE  ACTIVITIES  AT  EU  LEVEL: 

SHORT DESCRIPTION AND ESTIMATED COSTS  

The  revised  pharmacovigilance  legislation23  introduced  a  wide  range  of  changes  to  the  EU 
system of pharmacovigilance with implications both for the pharmaceutical industry as well 
as  for  the  competent  authorities.  This  Annex  outlines  the  activities  which  imply  the 
involvement of EMA, including rapporteurs from the MS.24 

The  costs  of  the  pharmacovigilance  activities  at  EU  level  and,  where  applicable,  of  the  MS 
acting as rapporteurs are estimated in Table 6. They are divided into four categories, (1) costs 
for assessment of PSURs25, (2) costs for assessment of PASSs26, (3) costs for assessment in 
the framework of Pharmacovigilance Referrals and (4) other costs of the EMA which cannot 
be directly linked to any of the three above procedures.  

The overall estimated cost for these activities is € 38.5 mil. Of this figure, € 28 mil. (ca. 73 %) 
amount  for  the  direct  cost  to  the  EMA  and  €  10.5  mil.  (ca.  27  %)  represent  the  cost  of  the 
NCA with respect to their responsibilities of conducting the scientific work as rapporteurs.  

The  cost  of  procedure-based  activities  (PSURs,  PASS  and  Pharmacovigilance  Referrals) 
amounts  to  €  11.3  mil,  €  1.5  mil.  and  €  6.7  mil.
  respectively.  In  overall  amounts,  this 
corresponds to: 

• 
• 

€ 9.2 mil costs of the EMA 
€10.3 mil costs of the MS rapporteurs 

The cost for other pharmacovigilance activities of the EMA not directly linked to any of the 
above procedures is estimated at € 19.1 mil.  

These figures, as well as estimations of the number of chargeable units in terms of MAH, MA 
and  EVcodes27  serve  as  a  basis  for  calculating  the  fees  to  be  charged  by  the  EMA  for  the 
pharmacovigilance activities as well as for the purposes of assessment of different options to 
collect the fees. This is dealt with in Annex 4. 

With  regard  to  the  administrative  costs  for  the  actual  collection  of  the  fees,  Table  7  below 
outlines  the  number  of  envisaged  transactions  per  EV-code,  number  of  envisaged  invoiced 
parties  as  well  as  estimated  costs  for  such  activities.  EMA  has  not  yet  implemented  the 
registration of entitlements outside the financial system with monthly reconciliation. Option 2 
would  require  this  level  of  web-based  automation  and  is  envisaged  to  be  introduced  in 
2014/2015.  Thus,  no  additional  cost  to  include  an  annual  pharmacovigilance  flat  fee  is 
expected.  The  same  automation  would  also  be  attractive  for  option  3  despite  the  fact  that 

23 Regulation (EU) No 1235/2010 amending Regulation (EC) No 726/2004 and Directive 2010/84/EU amending 
Directive 2001/83/EC 
24 The pharmacovigilance activities introduced by the revised legislation on pharmacovigilance are undertaken 
by  the  EMA  and  scientific  evaluation  within  these  EU  procedures  is  performed  by  the  rapporteurs  and  co-
rapporteurs from the NCAs appointed for the individual procedures. Rapporteurs should be remunerated by the 
EMA for the work that they provide.   

25 Periodic Safety Update Reports 
26 Post-Authorisation Safety Studies 
27 See Annex 1 

EN 

37 

   EN 

 
 
 
 
 
 
 
 
                                                 
options  3  might  be  administratively  more  complicated.  The  additional  fee  processing  for 
multiple MAH per procedure is estimated at € 450 000. The estimated administrative costs are 
added  to  figures  on  pharmacovigilance  activities  and  are  calculated  in  under  each  option  in 
Annex 4.   

Pharmacovigilance activities et EU level – some basic explanations 

Database of medicinal products for human use authorised in the EU ('Article 57(2) database') 

Marketing-authorisation  holders  were  required  to  submit  electronically  to  the  EMA 
information  on  all  human  medicines  authorised  in  the  EU  by  2  July  2012.  Current  non-
validated  data  from  the  database  suggests  that  there  are  in  total  some  9000  active 
substances/combination of substances in the EU (approximately 50% of these are authorised 
only in one MS and 50% in more than one MS). Information included in this database is used 
for  the  purposes  of  calculating  the  fees  and  it  is  proposed  that  the  EMA  use  records  in  the 
same database to underpin its invoicing activities. 

Reporting of Adverse Drug Reaction (ADRs) 

Under  the  previous  system,  marketing  authorisation  holders  submitted  adverse  reaction 
reports to the NCAs and in some cases also to the Eudravigilance (EV) database held by the 
EMA, depending on the route of authorisation, the seriousness of the reaction and the type of 
reporter.  With  the  revised  pharmacovigilance  legislation,  this  system  has  been  streamlined 
and it is foreseen that once the EV database has achieved its full functionality, all reports will 
be  sent  by  marketing  authorisation  holders  to  the  EV  database  only  (during  the  current 
transitional phase, the reports are also sent to the MS).  

The MAHs previously had the responsibility to monitor the literature for reports of ADRs and 
subsequently submit the reports. In future, the EMA will monitor selected active substances in 
selected medical literature and will also enter the ADRs found in this literature into the EV 
database. It is thus expected to reduce the number of duplicate entries. 

Periodic Safety Update Report (PSUR) requirements 

Previously  a  PSUR  would  be  submitted  on  regular  intervals  to  all  the  national  competent 
authorities where the same medicinal product was authorised, followed by an outcome of the 
assessment from each of the NCAs involved. Those PSURs and the related assessment reports 
were  to  a  large  extent  repetitive.  Some  NCAs  charge  a  specific  fee  for  the  submission  of 
PSURs whilst others include it in their national annual fee (see Table 1 in the main part of this 
impact assessment report for some indicative information). 

With the revision of the legislation, this has changed as the PRAC has established reference 
dates and submission frequencies for products with the same active substance or combination 
of  active  substances,  where  this  substance  (or  combination  of  substances)  is  authorised  in 
more than one MS. The European Reference Date list ('EURD" list, see Annex 1 for a brief 
explanation) that has been published by the EMA in October 2012 will take partially effect on 
1  April  2013  and  is  expected  to  be  fully  applicable  by  the  time  when  fees  for 
pharmacovigilance will be introduced. It currently contains some 3350 entries corresponding 
to active substances and combination of substances, as a result of which approximately 600 
substances (or combinations) are subject to PSUR submission annually (on average). An EU-

EN 

38 

   EN 

 
 
 
 
 
 
 
 
 
wide single assessment procedure will apply to PSURs submitted by the MAHs according to 
the  EURD  list  (one  submission)  and  will  result  in  a  single  outcome  of  such  an  assessment. 
Generic, well established use, homeopathic and traditional use herbal products use are, under 
the 2010 pharmacovigilance legislation, exempted from submitting PSURs (as these products 
are considered to have a well-established safety profile), unless obligations to the contrary are 
specified  as  conditions  to  the  marketing  authorisation,  the  submission  is  requested  by  the 
competent  authority  and  the  products  are  specifically  included  on  the  EURD  list  of 
harmonised 
active 
substances/combination  of  substances  included  in  the  current  EURD  list,  require  PSUR 
submissions  also  for  generics.  Overall,  this  new  EU-wide  procedure  for  the  assessment  of 
PSURs will greatly decrease the workload for the MAHs as well as the administrative burden 
of supplying PSURs to different MSs and paying the corresponding fees. 

submissions.  Currently, 

approximately 

10% 

the 

all 

of 

Oversight and submission of Post-Authorisation Safety Studies (PASS) 

The EMA will be involved in approval of protocols, amendments to the protocols and in the 
assessment  of  the  study  reports  conducted  in  the  post-authorisation  phase.  The  requirement 
relates  to  non-interventional  studies  involving  safety  data  from  patients  or  healthcare 
professionals where the studies have been requested as an obligation to the initial marketing 
authorisation  or  as  an  obligation  to  the  marketing  authorisation  in  the  post-authorisation 
phase, where the study will be conducted in more than one MS. In respect of obligations to 
conduct  studies  imposed  after  the  granting  of  the  marketing  authorisation,  the  2010 
pharmacovigilance legislation encourages MAHs to submit joint studies if the same concern 
about the risk of an authorised medicinal product relates to more than one medicinal product. 

Pharmacovigilance referrals 

A  pharmacovigilance  referral  is  a  centralised  procedure  used  to  resolve  concerns  over  the 
safety  of  a  medicine  or  a  class  of  medicines.  A  referral  resulting  from  the  evaluation  of 
pharmacovigilance data will always involve the PRAC and can be triggered either when 'EU 
interest' is considered to be involved or under the new 'Urgent EU procedure'. It is proposed 
that a pharmacovigilance referral fee is charged in any of these cases as the procedure will be 
the same. 

Estimation of the costs for pharmacovigilance activities at EU level 

The costs of the pharmacovigilance activities within the responsibilities of the EMA are 
estimated in Table 6.  

The administrative costs of invoicing the pharmacovigilance activities for the various options 
considered are estimated in Table 7. 

Table 8 provides details of the background data on which the estimates are based.

EN 

39 

   EN 

 
 
 
 
 
 
 
 
 
Table 6: Estimation of costs for Union-wide pharmacovigilance activities (in EUR) 

Activities 

EMA staff 

No. of 
hours 
required 

Tarrif per 
hour / 
hourly 
wage 

Estimated 
Frequency 
per year 

Overall cost 

NCA staff 

No. of 
hours 
required

Tarrif 
per hour 
/ hourly 
wage 

Estimated 
Frequency 
per year 

Total costs 
EMA + 
NCAs 

Overall cost 

R
U
S
P

S
S
A
P

1 

2 

3 

4 

5 

6 

6a 

7 

8 

9 

10 

11 

Preparation of list of harmonised submission dates 
for selected active substances 

Preparation of PRAC advice and updated EURD list 
following request for changes from MAH3 

Validation of PSUR, preparation of data for 
Rapporteur from Eudravigilance database and other 
sources4 

Preparation of PRAC, CHMP/CMDh outcome 

PRAC Staff time related to PSUR 

CHMP/CMDh Staff time related to PSUR 

Actual evaluation/assessment of PSUR applications 
by NCAs -  activity of raporteurs  

53,75

124,1

2 

€13 341   

21,5

11,9

5,1
21,2
9,1
81
81
27
40,5

124,1

124,1

79,5
124,1
79,5
124,1
79,5
124,1
79,5

10 

€26 682   

600 

€886 074   

600 
600 
600 
11 
11 
11 
11 

€243 270   
€1 578 552   
€434 070   
€110 573

€70 835   
€36 858
€35 417   

194

32

109

109

11

11

€232 606   

€38 368   

116

109

600

€7 586 400   

€3 435 671   

€7 857 374 €11 293 045 

l

o
c
o
t
o
r
P
S
S
A
P

Preparation of request including scientific questions 
and pre-submission meeting 

Summary outcome of protocol and outcome 
documents for PRAC 
Summary outcome of protocol amendments and 
outcome documents for PRAC3 
Summary of study report and outcome of report 
documents for PRAC and CHMP/CMDh4 

PRAC Staff time related to PASS 

25

124,1

35 

€108 588   

42,5

124,1

35 

€184 599   

27,5

124,1

35 

€119 446   

60
54
54

124,1
124,1
79,5

35 
11 
11 

€260 610   
€73 715
€47 223   

130

109

11

€155 870   

EN 

40 

EN 

 
  
  
  
  
  
  
  
 
  
  
  
  
  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
 
 
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
 
 
  
  
  
  
  
  
  
  
  
  
  
 
 
  
  
  
  
  
 
  
  
  
  
 
  
  
  
  
  
  
n
o
i
t
a
i
t
i
n

I

t
n
e
m

s
s
e
s
s
A

-

t
s
o
p

t
n
e
m

s
s
e
s
s
a

12 

12a 

13 

14 

15 

16 

17 

17a 

s
l
a
r
e
f
f
e
R
e
c
n
a

l
i

g
i
v
o
c
a
m
r
a
h
P

CHMP/CMDh Staff time related to PASS 

Actual evaluation/assessment of PASS applications by 
NCAs - activity of raporteurs  

27
40,5

124,1
79,5

11 
11 

€36 858
€35 417   

32

109

11

€38 368   

116

109

35

€442 540   

€866 456   

€636 778

€1 503 234 

 Preparation of procedure including scope of 
procedure, identification of products involved, List of 
Questions, analyses of in-house data1 

73,8

73,8

124,1

79,5

40 

40 

€366 343   

€234 684   

Preparation of outcome documents for PRAC and 
CHMP/CMDh (temporary measures, list of 
outstanding issues, recommendations, opinions), 
analyses of in-house data, organisation of oral 
explanations, scientific advisory groups/expert 
meetings and public hearin 

Preparation and publication of information on 
webportal, communication, translations, access to 
document requests and re-examinations as 
applicable3 

PRAC Staff time related to referrals 

CHMP/CMDh Staff time related to referrals 

Actual evaluation/assessment of Refferals 
applications by NCAs - activity of raporteurs  

300

124,1

40 

€1 489 200   

300

79,5

40 

€954 000   

193,75

124,1

40 

€961 775   

193,75

54
54
54
81

79,5

124,1
79,5
124,1
79,5

40 

11 
11 
11 
11 

€616 125   

€73 715
€47 223   
€73 715
€70 835   

130

65

109

109

11

11

€155 870   

€77 935   

360

109

40

€1 569 600   

€4 887 616   

€1 803 405

€6 691 021 

e
r
u
t
a
r
e
t
i
L

g
n
i
r
o
t
i
n
o
m

  18 

  19 

Outsourced literature monitoring and entering of 
data in EudraVigilance 

Quality control of the outsourced activities and 
entered data 

8153

124,1

1 

€1 011 787   

4455

124,1

1 

€552 866   

EN 

41 

EN 

 
  
  
  
  
  
  
  
 
 
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
  
 
 
 
 
  
  
  
  
  
  
  
  
  
  
 
 
  
  
  
  
  
  
 
 
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
 
 
 
  
  
  
  
 
 
 
  
  
  
  
ICT 

t
n
e
m
e
g
a
n
a
m
k
s
i
r
+
g
n

i
l

d
n
a
h
s
R
D
A
+
n
o
i
t
c
e
t
e
d

l

a
n
g
S

i

  22 

23 

24 

25 

26 

27 

s
r
e
h
t
O

IT development and software maintanace 

IT infrastructure maintanace  

Scientific validation of product and substance data 
submitted by the MAHs (outsorced) 

Clinical validation of signals, signal management by 
scientific staff and provision of analysis from 
EudraVigilance database and other data sources at 
the request from MS  
Management of RMPs including procedural support 
through PRAC, monitoring the outcome of risk 
minimisation measures and preparation of 
documents for publication for CAPs and for NAPs at 
the request of a member state. 

Monitoring the effectiveness of public health 
measures (e.g. risk management systems, through 
outsources studies of their outcomes using 
longitudinal patient databases). 

Pharmacovigilance inspections, information 
gathering on non-compliance and follow-up 

Translations of communication related material and 
of data received from the public in relation to 
referrals 

28   
29   
30   

  PRAC Staff time (remaining) 

  PRAC meeting costs 
  CHMP meeting costs 

  Total costs for Pharmacovigilance 

€4 882 643   

€2 061 636   

22390

124,1

1 

€2 778 599   

10 197 

124,1

1 

 € 1 265 455 

2 499 

79,5

1 

 €    198 670 

17820

124,1

1 

€2 211 462   

6534

79,5

1 

€519 453   

7643

6534
3861

3370
891
891

124,1

124,1
79,5

124,1
124,1
79,5

1 

1 
1 

1 
1 
1 

€948 496   

€810 869   
€306 950   

€418 217   
€110 573   
€70 835   

€564 503
€112 901   
€18 825 914   

€28 015 657   

194

109

11

€232 606   

€232 606 €19 058 520 

€10 530 163 €38 545 820 

Source: SANCO/EMA  
* EMA hours required for a given activity are weighted averages of min/max workload as estimated by the EMA based on the likelihood of procedures being minimum or maximum 
labour intensive; average EMA staff costs are calculated on the basis of EMA basic data sheet (Table 8 of this Annex) 
**  Cost  estimations  of  the  rapporteurs  from  NCAs  are  based  on  a  pilot  costing  exercise  of  NCAs  from  2009  attempting  to  assess  the  real  costs  of  MS  rapporteur’s  scientific 
evaluations;  in the current costing, it was assumed that time spent on PSURs / PASS assessment will on average be equal to the average time spent by NCA rapporteurs on Renewals 

EN 

42 

EN 

 
  
 
 
  
 
 
  
  
  
  
  
  
  
 
 
  
 
 
  
  
  
  
  
  
  
 
 
 
  
  
  
  
 
 
  
  
  
  
  
 
 
  
  
  
  
  
 
 
  
  
  
  
 
 
  
  
  
  
 
 
  
  
  
  
 
 
  
  
  
  
 
 
  
  
  
  
 
 
 
 
 
 
 
 
 
 
  
  
  
  
 
 
 
 
  
  
  
  
 
 
  
  
  
  
 
  
  
  
 
 
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
in  the  centralised  procedure    and  the  average  time  spent  on  Pharmacovigilance  Referrals  will  be  equivalent  to  the  average  of  time  spent  on  "abridged  application"  and  "full 
application"  for a centralised MA as declared in the 2009 exercise. Average personnel cost per hour reported by the participating NCAs (i.e. € 100.5 ) was adjusted taking into 
account the inflation as reported by Eurostat for 2010 -2012 (i.e. 2.1 %, 3.1 % and 3 % respectively). 
*** PRAC/CHMP meeting costs are calculated assuming that one MS representative per meeting is sufficient 
1 Includes: preparation of list of substances and sending it to NCAs, consolidation of comments and timeframes and sending consolidated list to NCAs, finalisation of list including 
identified issues, PRAC review, sending list to CHMP and CG and publication of list. 
2 Includes: preparation of outcome i.e. PRAC advice and updated list, following CHMP/CMDh discussion and publication of revised list if applicable. 
3  Includes:  technical  validation  (depending  on  number  of  PSURs  per  assessment),  preparation  of  data  for  rapporteurs  in  the  form  of  analyses  of  EU  data-sources,  notably 
EudraVigilance ADR data, liaison with MAH(s). 
4 Check of assessment report for confidential information and redaction if necessary, arranging oral explanation for the PRAC if necessary, preparation of PRAC recommendation 
(depending on number of PSURs per assessment), arrange oral explanation for the CHMP if necessary, preparation of CHMP opinion, preparation of web portal documents and 
preparation of translations. 
10 Includes: preparation of summary report, preparation of PRAC LoQs if applicable and outcome documents and attending PRAC plus preparing outcome documents CHMP/CMDh 
if applicable and attending CHMP/CMDh discussion on report if applicable. 
14 Includes: preparation of temporary measures, SAG/expert meetings , arranging oral explanation for the PRAC if necessary, preparation of PRAC recommendation, analyses of in-
house  data,  public  hearings  if  necessary,  arrange  oral  explanation  for  the  CHMP  if  necessary,  preparation  of  CHMP/CMDh  opinion  if  applicable,  document  management  of 
submissions  from  various  stakeholders  including  the  public  following  announcement  of  the  referral  and  if  applicable  following  the  public  hearing,  interaction  with  stakeholders 
(MAHs, patients, HCP, investigators). 
20,21  Estimate  of  IT  costs  includes both  the  IT  projects  and  IT  Infrastructure  (Eudravigilance,  PSUR, signal  detection,  transparency,  technical  aspects  and  others)  as projected  by 
SANCO IT unit; the costs are calculated as average IT annual costs from the projected period of 2012-2016 

EN 

43 

EN 

 
  
 
 
 
 
Table 7: Estimation of administrative cost of invoicing the pharmacovigilance activities per EV-code 

Option 1 - no 
PhV fees 

Option 2 - flat fee 

Option 3 - procedure based 
fee and flat fee 

Option 4 - only procedure 
based fee 

Assumptions 

Flat fee 

PSUR 

PASS 

Referral 

Total 

Transactions 
Invoiced parties 
Transactions  
Invoiced parties 
Transactions 
Invoiced parties 
Transactions 
Invoiced parties 
Transactions 
Invoiced parties 

AD staff 
AST staff 
Total 

Costs 

0 
0 
0 
0 
0 
0 
0 
0 
12952* 
5828 

€67 150 
€86 059 
€153 209 
Covers  all  EMA 
fee  transactions 
in 2012 

ICT requirements 

359883 
10826 
0 
0 
0 
0 
0 
0 
359883 
10826 

€0 
€0 

€0 

is 
Web-based  automation 
envisaged  for  EMA  flat  fee 
transactions 
in  2014/15, 
with  negligible  additional 
include  the  new 
cost  to 
pharmacovigilance flat-fee 
Web-based  automation  for 
invoicing/pre-payment  

financial 

1 
transaction 
(manual  per  month)  as  per 
FFR 

359883 
10826 
33600 
1800 
35 
35 
4280 
1440 
397798 
14101 

€196 570 
€251 926 

€448 496 
fee 

processing 

for 
Additional 
multiple MAH per procedure require 
estimated  1  AD  and  2  AST  staff.  
Average 
fee 
transaction on an invoice is 8 min. 

time  needed  per 

 based on EV-CODE  

 600 PSURs * 56 EV-CODEs  

 600 PSURs * 3 MAHs  

 35 PASS  

 35 PASS * 1 MAH  

 40 Referrals * 107 EV Codes  

 40 Referrals * 36 MAH  

0 
0 
33600 
1800 
35 
35 
4280 
1440 
37915* 
3275 

€196 570 
€251 926 

€448 496 
Fee  processing  for  multiple  MAH 
per  procedure  require  estimated 
1  AD  and  2  AST  staff.    Average 
time  needed  per  fee  transaction 
on an invoice is 8 min. 

Web-based 
invoicing/pre-payment  

automation 

for 

Adaption of SAP interface and/or use 
of automation above 

Adaption  of  SAP  interface  and/or 
use of automation above 

EN 

44 

EN 

 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
based 

Development  in  SAP  to  allow  for 
transactions. 
procedure 
Current  system  is  set  up  for  1:1 
procedure:MAH, 
option  would 
assume 1:many procedure:MAH 

Development  in  SAP  to  allow  for 
transactions. 
procedure  based 
Current  system  is  set  up  for  1:1 
procedure:MAH,  option  would 
assume 1:many procedure:MAH 

Development  in  SAP  to  allow  for 
different  fee  per  invoiced  party  per 
procedure + increased administraive 
burden  for  processing  and  changing 
thereof. 

Development  in  SAP  to  allow  for 
different  fee  per  invoiced  party 
increased 
per 
administraive 
for 
processing and changing thereof. 

procedure 

burden 

+ 

Source: EMA 
* Estimated 37,915 fee transactions for the procedure-based pharmacovigilance fees. This represents approximately  a three-fold increase to the current volume of all EMA fee 
transactions of 12,952 (2012) 

EN 

45 

EN 

 
  
  
  
  
  
  
  
 
 
2012 
366 
-105 
-18 
-29 
-9 
-7 
198 
2012 
8 * 
198  
1,584  
2012 
138,579  
38,304  

2016 
365 
-104 
-17 
-29 
-9 
-7 
199 
2016 
8 * 
199  
1,592  
2016 
142,655  
32,415  

Table 8: EMA basic data sheet used for calculations of the costs for Pharmacovigilance 
activities 
1. Productive working days/year 
Number of days/year 
- less weekends 
- less bank holidays 
- less average leave days 
- less average sick leave days 
- less average training days 
Total number of productive days/year 
2. Standard working hours/year 
Standard working hours/day 
x number of productive days/year 
Total number of productive hours/year 
3. Average staff cost 
Average salary items AD (~ AD8) 
Overhead non-salary cost, building, 
equipment etc. 
Overhead for support and management  
(as per ABB)  
Total staff cost AD 
Average salary items AST (~ AST3) 
Overhead non-salary cost, building, 
equipment etc. 
Overhead for support and management  
(as per ABB)  
Total staff cost AST 
Average salary items Contract Agent (~ 
FG III) 
Overhead non-salary cost, building, 
equipment etc. 
Overhead for support and management  
(as per ABB)  
Total staff cost Contract Agent 

19,687 
(11.13%) 
196,570  
75,043  
38,304  

19,223 
(10.98%) 
194,293  
77,250  
32,415  

12,616 
(11.13%) 
125,963  
48,538  

 12,041 
(10.98%) 
121,706  
53,360  

9,666 
(11.13%) 
96,508  

 9,418  
(10.98%) 
95,193  

38,304  

32,415  

Notes: 
Weighting on salary items assumed 
(including exchange rate) 
Employers pension contribution included 
Source: EMA  
* A working week of 40 hours is applied to all calculations which already corresponds to the current reality and 
workload. 

2012 
148 

2016 
130 

yes 

no 

EN 

46 

   EN 

 
 
 
 
 
 
 
ANNEX  4  –  CALCULATION  OF  THE  AMOUNT  OF  FEES  FOR 

CONSIDERED OPTIONS   

This Annex outlines the calculations of the amount of the fees for each considered option. The 
calculations are based on the estimated costs of the pharmacovigilance activities outlined in 
Annex 3 and on the basic data estimations in Table 9 below.  

When  a  fee  taking  into  account  SMEs  reduction  is  calculated,  it  is  assumed  that  the  micro-
enterprises  will  be  entirely  exempted  from  the  obligation  to  pay  any  pharmacovigilance  fee 
whereas  the  small  and  medium-sized  enterprises  will  pay  60%  of  the  standard  fee.  Further 
detailed information on the numbers and breakdown of SMEs, how they would be impacted 
and justification for their potential exemption is provided in Annex 5. 

When  a  fee  taking  into  account  the  reductions  foreseen  for  certain  categories  of  medicinal 
products28 is calculated, it is assumed that the reduction of 20 % from the standard fee will 
apply to generics. The reduction for generics is applicable only to calculations related to any 
flat fee.   

8 869 

3 357 

10 826 
9727 

Table 9: Basic data 
Total number of MAH in EU 
Number  of  MAH  of  a  medicinal  product  with  active  substance 
authorised in more than 1 MS* 
Total number of active substances in corresponding to authorised 
products in the EU 
Number  of  active  substances  for  which  PSURs  are  required 
(EURD list) 
Total number of EV-codes in the EU 
Number of EV-codes for active substances on the EURD list  
    - EV-codes corresponding to generic products 
    - EV-codes corresponding to originator products 
Number  of  EV  codes  for  active  substances  on  EURD  list  for 
which PSUR is required29  
Total number of MA in EU 
Number of MA for active substances on the EURD list 
SMEs out of the total number of MAH 
Micro-enterprises out of SMEs 
EV-codes / MA held by SMEs 
EV-codes / MA held by micro-enterprise (out of SMEs)  
Source:  Art  57  database  as  of  February  2013  (data  under  validation);  EMA  SMEs  register;  EMA  database  of 
centrally registered products 
*Estimate based on cross-reference data extracts. 

288 133 
267 780 
90 % 
33 % 
10% 
25% 

383 395 
359 883 
49% 
51% 
189124 

28  Includes  authorised  generic,  homeopathic  and  herbal  medicinal  products  as  well  as  medicinal  products 

authorised on grounds of well-established medical use. 

29 EV codes of generic medicinal products are included for 10% of the substances. 

EN 

47 

   EN 

 
 
 
 
      
 
 
 
 
                                                 
Option 2: One flat fee covering all pharmacovigilance activities 

The costs of all Union-wide pharmacovigilance activities carried out in one are estimated at € 
38.5  mil.  In  order  to  cover  these  costs  through  a  single  annual  flat  fee,  three  scenarios  are 
considered.  

(A) Fee charged per Marketing authorisation holder (MAH) 

(B) Fee charged per EV-code 

(C) Fee charged per Marketing authorisation (MA) 

Table 10: Calculation of a single annual flat fee  

Chargeable 
unit 
(A) MAH 
(B) EV-CODE 
(C) MA 
Source: own calculations based on data from EMA   

unit no. 
9727 
359883 
267780 

standard 
fee (no 
reductions)
€3 963 
€107 
€144 

fee taking 
into 
account 
SMEs 
reduction 
€8 581 
€113 
€152 

fee taking 
into 
account 
generics 
reduction 
n.a. 
€122 
€165 

cost of SME 
reduction 
€20 745 360 
€2 126 498 
€2 120 020 

cost of generics 
reduction 
n.a. 
€5 559 233
€5 542 298

The most favourable scenario for this option is considered to be the fee paid on the basis of 
EV-codes  and  taking  into  account  the  reduction  of  40  %  for  SMEs  as  well  as  the  20  % 
reduction for generics which are not held by SMEs. The micro-enterprises would be exempted 
from paying the fee.  

Despite  the  fact  that  fee  determination  when  charging  per  MAH  would  be  simple  and 
straightforward,  it  would  not  respect  the  fairness  principle,  as  the  differences  between  the 
MAH and the number of products and presentations would not be taken into account. It would 
therefore not capture (even indirectly) the market share of the companies. Moreover, the  

calculations  show  that  the  fees  charged  by  MAHs  would  stay  beyond  any  reasonable 
proportions, i.e. in the case when reductions apply, the SMEs would have to pay more than if 
a standard fee without the reduction would be applied.   

Option 3: A combination of separate fees for procedure based activities and a flat fee for all 

other activities 

Periodic safety update reports (PSUR) 

The overall annual cost of pharmacovigilance activities related to the assessment of PSURs is 
estimated at € 11.3 mil. The average cost of a  PSUR assessment is estimated at € 18 822. In 
order to cover these costs through a fee, three scenarios per PSUR assessment are considered.   

(A) Fee charged per Marketing authorisation holder (MAH)  

(B) Fee charged per EV-CODE 

(C) Fee charged per Marketing authorisation (MA) 

EN 

48 

   EN 

 
 
 
 
 
 
 
 
Table 11: Calculation of PSUR fee 

Chargeable 
unit 
(A) MAH 
(B) EV-CODE 
(C) MA 
Source: own calculations based on data from EMA   

average 
no. / PSUR 
3 
56 
42 

standard 
fee  
€6.496 
€334 
€449 

fee taking 
into 
account 
SMEs 
€14.066 
€354 
€476 

fee taking 
into 
account 
generics 
reduction 
n.a. 
€390 
€524 

cost of 
SME 
reduction 
€12.400 
€1.035 
€1.035 

cost of 
generics 
reduction 
n.a. 
€2.711 
€2.711 

The most favourable scenario for this option appears to be the fee paid on the basis of EV-
codes  and  taking  into  account  the  reduction  for  SMEs.  The  reductions  for  generics  is 
questionable as in principle all companies should bear the costs of potential safety concerns 
usually  associated  with  PSUR  procedure,  once  it  has  been  decided  to  require  PSURs  for 
generics through the EURD substances list.  

In  practice  however,  charging  per  EV-code  might  lead  to  a  very  high  variability  in  the  fee 
revenue  per  procedure30  causing  disproportionality  and  unpredictability  of  revenues.  That  is 
why  the  most  reasonable  scenario  is  to  charge  a  fixed  overall  amount  of  €  18 822  per 
procedure increased for the administrative costs of actual fee collection of € 662 and to use 
EV-codes for the distribution of the fee among the MAHs. Given that the PSURs submission 
is specified in the EURD list, the MAHs will have sufficient information well in advance as to 
when they will be subject to the procedure.   

Post-authorisation safety studies (PASS) 

The overall annual costs of pharmacovigilance activities related to the assessment of PASSs 
are estimated at € 1.5 mil. The average cost of  a single PASS assessment thus amounts to € 42 
950. These estimations are based on 35 PASS per year. In order to cover these costs through a 
fee, it is reasonable to charge the fee per procedure, increased by the administrative cost for 
actual  collection  in  the  amount  of  €  12  per  PASS  and  divide  this  figure  by  the  number  of 
entities  taking  part  in  the  conduct  of  the  study.  The  number  of  entities  will  depend  on  the 
arrangements among the marketing authorisation holders for each case.  

Pharmacovigilance Referrals 

The overall costs of activities related to the assessment in case a pharmacovigilance referral 
are  estimated  annually  at  €  6.7  mil.  The  av erage  cost  of  a  pharmacovigilance  referral 
assessment  is  estimated  at  €  167  276.  This  is  based  on  40  estimated  Referrals  per  year.  In 
order to cover these costs through a fee, three scenarios are considered.  

(A) Fee charged per Marketing authorisation holder (MAH)  

30  Certain  substances  with  a  large  number  of  EV-codes  associated  (e.g  valsartan,  simvastatin,  among  others) 
could    lead  to  collecting  a  revenue  of  ca.  €  1.5  m  per  single  PSUR  assessment.  Other  substances  (e.g. 
triclosan, heparin among others) could  amount to a revenue of only € 668 per single PSUR assessment. 

EN 

49 

   EN 

 
 
 
 
 
 
 
 
                                                 
(B) Fee charged per EV-CODE 

(C) Fee charged per Marketing authorisation (MA) 

Table 12: Calculation of pharmacovigilance referral fee 

Chargeable 
unit 
(A) MAH 
(B) EV-CODE 
(C) MA 
Calculations based on data from EMA   

Av No. / 
active 
substance 
3 
56 
42 

standard 
fee  
€57 730 
€2 969 
€3 995 

fee taking 
into account 
SMEs 
€125 012 
€3 142 
€4 227 

fee taking 
into account 
generics 
reduction 
n.a 
€3 464 
€4 660 

cost of SME 
reduction 
€100 114 
€10 455 
€10 455 

cost of generics 
reduction 
n.a. 
€25 352 
€25 352 

The most favourable scenario for this option seems to be a fee paid on the basis of EV-codes 
and taking into account the reduction for SMEs. The reductions for generics is questionable as 
in principle all companies should bear the costs of potential safety concerns usually associated 
with a pharmacovigilance referral. 

In practice, however, this might lead to a very high variability in the fee revenue per single 
procedure  due  to  impossibility  to  estimate  the  real  number  of  MAHs  involved  in  it.  As  a 
consequence,  charging  an  amount  per  EV-code  would  lead  to  disproportionality  and 
unpredictability of revenues. 

That is why the most reasonable scenario is to charge a fixed overall amount of € 167 276 per 
procedure,  increased  by  €  1266  of  administrati ve  costs,  and  to  divide  the  fee  among  the 
MAHs based on the actual number of MAH taking into account the number of EV-codes that 
they hold.  

Non-procedure based activities 

The  costs  of  the  pharmacovigilance  activities  not  directly  related  to  any  of  the  three 
procedures above are estimated annually at € 18.8 mil. In orde r to cover these costs through 
an annual flat fee, three scenarios are plausible. 

Table 13: Calculation of a flat fee for a non-procedure based activities 

standard 
Chargeable 
fee (no 
unit 
reductions)
€1 935 
(A) MAH 
€52 
(B) EV-CODE 
(C) MA 
€70 
Calculations based on data from EMA   

unit no. 
9727 
359883 
267780 

fee taking 
into 
account 
SMEs 
reduction 
€4 191 
€55 
€74 

fee taking 
into 
account 
generics 
reduction 
n.a. 
€60 
€80 

cost of 
generics 
reduction 
n.a. 

cost of SME 
reduction 
€12 402 513 
€1 038 589  €2 715 149 
€1 035 425  €2 706 878 

The most favourable scenario for this option is considered to be the fee paid on the basis of 
EV-codes  and  taking  into  account  the  reduction  of  40  %  for  SMEs  as  well  as  the  20  % 
reduction for products with well-established safety profile such as generics which are not held 
by SMEs. The micro-business would be exempted from paying that fee.  

EN 

50 

   EN 

 
 
 
 
 
 
 
Despite  the  fact  that  fee  determination  when  charging  per  MAH  would  be  simple  and 
straightforward,  it  would  not  respect  the  fairness  principle,  as  the  differences  between  the 
MAH and the number of products and presentations would not be taken into account. It would 
therefore not capture (even indirectly) the market share of the companies.  

Option 4: Procedure based fees only 

The  overall  cost  of  Union-wide  pharmacovigilance  activities  carried  out  in  one  year, 
estimated  at    €  38.5  mil  (i.e.  €  19.5  mil  proce dural  related  costs  +  €  19  mil.  other  costs), 
would  be  covered  entirely  through  the  fees  collected  from  the  three  procedures,  i.e.  PSUR, 
PASS and Pharmacovigilance Referral. In common with the previous options, there are three 
scenarios for collecting the fees. Moreover, two different possibilities of attributing the non-
procedure related costs to the procedures are considered. 

(1)  Non-procedure  related  costs  equally  distributed  among  the  three  types  of 

procedures   

(2)  Non-procedure  related  costs  proportionally  distributed  among  the  three  types  of 
procedures, based on the workload involved within each type of procedures 

Periodic safety update reports (PSUR) 

The  overall  cost  of  pharmacovigilance  activities  related  to  the  assessment  of  PSURs  is 
estimated annually at € 11.3 mil. In case of a ttributing the proportion of non-procedure related 
costs  in  addition,  the  cost  for  assessment  of  PSURs  would  increase  to  €  16.2  mil.  when 
distributing equally or to € 19.9 mil. when dist ributing proportionally. The average cost of a 
single  PSUR  assessment  would  thus  amount  to  €  27 053  or  €  33  132  respectively.  This  is 
based  on  estimated  600  PSURs  per  year.  In  order  to  cover  these  costs  through  a  fee,  three 
scenarios per PSUR assessment are considered.   

Table 14: Calculation of a PSUR fee increased by costs of non-procedure based activities 

Chargeable unit 
(A) MAH 

(1) equal 
distribution 

(B) EV-CODE 

(C) MA 

average 
no. / 
PSUR 
3 

56 

42 

(A) MAH 
(2) 
proportional 
(B) EV-CODE 
distribution 
(C) MA 
Calculations based on data from EMA   

3 
56 
42 

fee taking 
into 
account 
SMEs 
€19 486 

€557 

€749 

€24 667 
€705 
€948 

standard 
fee  
€9 120 

€522 

€702 

€11 544
€661 
€889 

fee taking 
into 
account 
generics 
reduction 
n.a 

€614 

€827 

n.a. 
€778 
€1 046 

cost of SME 
reduction 
€15 646 

€1 838 

€1 838 

€19 806 
€2 327 
€2 327 

cost of 
generics 
reduction 
n.a. 

€4 457 

€4 457 

n.a. 
€5 642 
€5 642 

The proportional distribution of the non-procedure related costs within the fee is considered as 
the most suitable and fair option. The most favourable scenario for this option seems to be a 

EN 

51 

   EN 

 
 
 
    
 
 
 
 
fee  paid  on  the  basis  of  EV-codes  and  taking  into  account  the  reduction  for  SMEs.  The 
reduction for generics is  questionable as in principle all companies  should bear  the  costs of 
potential safety concerns usually associated with PSUR procedure, once it has been decided to 
require PSURs for generics through the EURD substance list.  

In  practice,  however,  this  might  lead  to  a  very  high  variability  in  the  fee  revenue  per 
procedure31 causing disproportionality and unpredictability of revenues. That is why the most 
reasonable scenario is to charge a fixed overall amount of € 33 132 pe r procedure increased 
by  the  administrative  costs  of  fee  collection  of  €  662  and  di vide  the  fee  among  the  MAHs 
based  on  the  proportion  of  EV-codes  for  each  MAH.  Given  that  the  PSURs  submission  is 
specified in EURD list, the MAHs will have sufficient information well in advance as to when 
they will be subject to the procedure.   

Post-authorisation safety studies (PASS) 

The  overall  cost  of  pharmacovigilance  activities  related  to  the  assessment  of  PASSs  is 
estimated annually at € 1.5 mil. In case of a ttributing the proportion of non-procedure related 
costs in addition, the cost for assessment of PASS would increase to € 7.8m when distributing 
equally  or  to  €  3m  when  distributing  propor tionally.  The  average  cost  of  a  single  PASS 
assessment  would  thus  amount  to  €  224 459  or 
estimated  PASS  per  year.  In  order  to  cover  these  costs  through  a  fee,  considering  the 
proportional distribution of the non-procedure related costs within the fee as the most suitable 
and  fair  option,  the  fee  per  procedure  would  amount  to  €  84954,  adding  the  €12  for 
administrative  costs  and  dividing  this  figure  by  the  number  of  entities  taking  part  in  the 
conduct  of  the  study.  The  number  of  entities  will  depend  on  the  arrangements  among  the 
marketing authorisation holders for each case.  

€  84954  respectively.  This  is  based  on  35 

Pharmacovigilance referrals 

The  overall  costs  of  pharmacovigilance  activities  related  to  the  assessment  in  case  of  a 
pharmacovigilance  referral  are  estimated  annually  at  €  6.7  mil.  In  case  of  attributing  the 
proportion  of  non-procedure  related  costs  in  addition  to  this,  the  costs  for  referrals  would 
increase to € 13m when distri buting equally or to € 13.2m wh en distributing proportionally. 
The average cost of a referral would thus amount to € 326 097 or € 330870 respectively. This 
is based on estimated 40 pharmacovigilance  referrals per year. In order to cover these costs 
through a fee, three scenarios are considered.   

31 Certain substances (e.g. valsartan, simvastatin) could lead to a revenue of € 3.4m per PSUR assessment. Other 

substances (e.g. triclosan, heparin) could cause the fee revenue to drop to only € 1400. 

EN 

52 

   EN 

 
 
 
 
 
                                                 
Table  15:  Calculation  of  a  Pharmacovigilance  referral  fee  increased  by  cost  of  non-
procedure based activities 

Av No. / 
active 
substance
3 

standard 
fee  
€112 543

fee taking 
into 
account 
SMEs 
€243 705 

Chargeable unit 
(A) MAH 

(1) equal 
distribution 

(B) EV-CODE 

(C) MA 

56 

42 

€5 788 

€6 125 

€7 787 

€8 240 

(A) MAH 
(2) 
proportional 
(B) EV-CODE 
distribution 
(C) MA 
Calculations based on data from EMA   

3 
56 
42 

€114 191
€5 873 
€7 901 

€247 273 
€6 215 
€8 361 

fee taking 
into 
account 
generics 
reduction 
n.a. 

€6 752 

€9 084 

n.a. 
€6 851 
€9 217 

cost of SME 
reduction 
€195 169 

€20 381 

€20 381 

€198 026 
€20 679 
€20 679 

cost of 
generics 
reduction 
n.a. 

€49 422 

€49 422 

n.a. 
€50 145 
€50 145 

The proportional distribution of the non-procedure related costs within the fee is considered as 
the most suitable and fair option. The most favourable scenario for this option would be a fee 
paid on the basis of EV-codes and taking into account the reduction for SMEs. The reduction 
for  generics  is  questionable  as  in  principle  all  companies  should  bear  the  costs  of  potential 
safety concerns usually associated with a pharmacovigilance referral procedure. 

In  practice  however,  this  might  lead  to  a  very  high  variability  in  the  fee  revenue  per  actual 
procedure  due  to  impossibility  to  estimate  the  real  number  of  MAHs  involved  in  it.  As  a 
consequence,  charging  an  amount  per  EV-code  would  lead  to  disproportionality  and 
unpredictability of revenues. 

That is why the most reasonable scenario is to charge a fixed overall amount of € 330 870 per 
procedure and active substance, increased by € 1266 of administra tive costs, and  to divide the 
fee among the MAHs based on the real number of MAH taking into account the proportion of 
EV-codes that they hold .  

GROUPING FOR THE PURPOSES OF PHARMACOVIGILANCE FEES   

The  public  consultation  paper  had  put  forward  for  discussion  the  assumption  that  MAHs 
concerned  by  one  assessment  would  form  a  group  and  that  the  fee  would  be  shared  among 
members of the group. 

While  a  number  of  respondents  supported  the  concept  in  general,  as  a  means  to  reduce  the 
actual amounts to be paid, most of the comments considered the concept to be very difficult to 
apply in practice. It was referred to the need to clarify whether MAHs belonging to the same 
mother company or group of companies, MAHs having concluded agreements or exercising 
concerted practices as regards the placing on the market of the medicinal product(s), should 
be taken as ‘the same marketing authorisation holder’ (as per Commission Communication OJ 
C 229, 22 July1998).  

On the other hand, it should be noted that the EMA has experience with grouping only for the 
purpose  of  active  participation  in  referral  procedures  as  such  and  it  is  unclear  whether  the 
possible grouping for the payment of a fee would follow the same pattern. Moreover, there is 
currently  no  available  structured  information  on  the  ownership  relationship  amongst  MAH 

EN 

53 

   EN 

 
 
 
 
 
 
 
throughout the EU, which could have been used as a possible indicator to estimate the degree 
of  grouping  for  the  payment  of  a  given  type  of  fee.  This  uncertainty  makes  it  virtually 
impossible to predict with  any  degree of precision how MAH would possibly group  for  the 
payment of fees.  

These consideration lead to the following orientations per procedure, which are relevant to the 
estimation of the fee levels and to the way fees would be charged. 

PSUR assessment 

Following feedback that was received during the public consultation, grouping for submitting 
PSURs is considered very unlikely in practice (sharing of commercial data, different standard 
operating  procedures,  difficulty  to  divide  the  work  and  to  coordinate  between  different 
QPPVs,  etc.),  except  for  entities  belonging  to  the  same  mother  company.  In  this  respect, 
producing a single PSUR with all the information, data and analysis coming from independent 
companies  seems  unrealistic.  This  leads  to  an  uncertainty  over  the  number  of  products  and 
MAH  concerned  by  one  PSUR,  as  well  as  an  uncertainty  over  the  number  of  individual 
PSURs submitted in the framework of a single PSUR assessment of a given substance. It is 
therefore reasonable to lower the level of the chargeable unit (and, respectively, the unit for 
the  calculation  of  the  applicable  fee)  from  the  entire  procedure  to  MAHs  or  authorisations. 
For the sake of predictability and proportionality, a minimum and a maximum total amount 
that  the  EMA  should  collect  per  PSUR  assessment  could  be  foreseen  in  order  to  avoid 
extremes. This approach was explored in the different options, however the results of it would 
not  be  in  line  with  the  objective  of  a  cost-based  fee  and  practical  difficulties  of  setting  the 
minimum  and  maximum  levels  arise.  This  would  ultimately  increase  the  uncertainty  of 
funding the pharmacovigilance activities, as the distribution of active substances, the number 
of  EV-codes  involved,  the  number  of  MAHs  involved  and  the  relationship  between  these 
variables  can  not  be  established  with  a  sufficient  degree  of  precision.  Consequently,  the 
preferred  approach  is  to  distribute  the  amount  of  the  fee  among  the  MAHs  involved 
proportionately to the respective number of chargeable units.  

PASS assessment 

Respondents to the public consultation considered grouping for PASS as an option but draw 
the attention to some practical/legal constraints (e.g. a PASS is imposed on one MAH but the 
study is conducted by several MAH jointly). Therefore, where PASS are conducted jointly by 
different  MAHs,  it  is  reasonable  to  keep  the  charging  at  the  level  of  the  procedure,  i.e.  the 
assessment of the study, as the number of MAH or the number of MA in their portfolio would 
not  have  a  significant  impact  on  the  assessment  effort.  In  case  of  a  joint  submission,  the 
amount could be divided by charging equally MAHs that have the obligation to conduct the 
PASS assuming that any further division between all MAHs that have taken part in the PASS 
could be arranged for by the MAHs themselves. 

EN 

54 

   EN 

 
 
 
 
 
 
Pharmacovigilance referral 

The concept of grouping was considered by respondents to the consultation more relevant in 
the  case  of  pharmacovigilance  referrals,    but  several  respondents,  notably  the  generics 
industry, request clarification about how the fee would be divided. In order to be connected to 
the  assessment  effort  and  bearing  in  mind  the  need  of  predictability  and  proportionality,  a 
similar approach to the assessment of PSURs was taken, i.e. using the chargeable unit at the 
level of MAs (EV-codes) for a proportionate division among the MAHs involved..  

EN 

55 

   EN 

 
 
 
 
ANNEX 5 – SMES ASPECTS OF THE ASSESSMENT   

In the European Union overall, there are some 10 82632 MAHs having at least one marketing 
authorisation of a medicinal product.  The estimate on the proportion of SMEs is 90 %33. The 
micro-enterprises represent 33 % of the MAHs within the SMEs category34.   

As  regards  EV-codes  and  marketing  authorisations  (MA),  the  estimated  values  used  in  this 
impact assessment are given in Table 16 below. For the purposes of fee calculations in Annex 
4, the percentages of EV codes (1.44 %) and MAs (1.67 %) held by SMEs were adjusted to 
10 % due to the probable residual non-compliance in Article 57(2) database.  

Table 16: Estimates of chargeable units - EV codes and MA, per category of MAH 
Non-SMEs 

EV codes 

MAHs 

MAs 

CAP 

Non-CAP 

Total 

29951 

353444 

383395 

9339 

278794 

288133 

3293 

30% 
EV codes 

MAHs 

SMEs 
CAP 
Non-CAP 
Total 
-  of which micro 
 Source: EMA, Art 57 database, situation as of February 2013  
*adjusted figure 

EV codes 
1034 
4500 
5534 
1399 

MAs 
823 
3992 
4815 
1231 

247 
82 

held by SME  MA held by SMEs 

1,44%  (10%)* 
25% 

1,67%  (10%)* 
26% 

The proposed SME reductions are based on the comparisons of added values per employee as 
a possible measure of profitability of companies. Using this measure, the small and medium 
enterprises in the pharmaceutical sector are on average 40 % less profitable than non-SMEs, 
as indicated in Table 17 below. The micro-enterprises are 60 % less profitable per employee 
than the big pharmaceutical companies. Accordingly, it is assumed that the small and medium 
enterprises  should  be  charged  60  %  of  the  standard  fee,  whereas  the  micro-enterprises  are 
assumed  to  be  entirely  exempted  from  the  obligation  to  pay  pharmacovigilance  fees.  The 
underlying  reason  for  exempting  the  micro-enterprises  is  the  fact  that  the  already  small 
number  of  EV-codes  held  by  SMEs  is  further  decreased  by  a  factor  of  4  in  case  of  micro 
enterprises , which implies that the administration burden of collecting the fee would exceed 
the  benefits  from  its  collection.  Furthermore,  this  is  in  line  with  the  general  EU  policy  to 
specifically  exempt  wherever  possible  micro-enterprises  from  EU  legislation  or  introduce 
special regimes so as to minimise the regulatory burden on them35.   

32  This  figure  represents  an  estimation  of  the  number  of  individual  MAHs  in  the  EU  as  of  February  2013  as 
registered in the EMA database (Art 57). A certain degree of non-compliance is posisble.   
33  The  estimate  is  based on  EMA  figures  as  of  February  2013.  The number  of non-SMEs  in  the  CAP  register 
amounts to 3293 MAHs. Projections of that figure would imply that ca. 70 % of MAHs are SMEs.  However, 
Eurostat data (NACE C21-manufacture of basic pharmaceutical products and pharmaceutical preparations; 2009-
2012) indicate that 90 % of pharmaceutical companies in the EU are SMEs and the latter figure was used in this 
impact assessment.       
34  This  estimation  is based on  the  proportion  of  micro-enterprises  (82) of  the  total number  of    SMEs  (247)  as 
currently registered in the EMA SME Register. 
35 COM(2011) 803 final. 

EN 

56 

   EN 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                 
2008 

2009 

Value added / employee 
2010 

Table 17: Value added per employee and type of company 
 Type of 
enterprise 
micro 
small 
medium 
SMEs 
Non-SMEs 
Calculations based on Eurostat SBS data 

64% 
48% 
60% 
57% 
100% 

40%
43%
62%
57%
100%

40%
44%
63%
58%
100%

40%
45%
66%
61%
100%

2011 

2012 

41%
44%
61%
57%
100%

The  impact  on  SMEs  for  all  the  options  for  fee  collection  is  calculated  in  Annex  4.  The 
calculations  show  that  for  the  preferred  option  the  increase  in  the  standard  flat  fee  due  to 
reductions  to  SMEs  would  be  only  marginal.  Furthermore,  the  administrative  burden  of 
collecting a small flat fee from micro-enterpriss would exceed the actual benefit of collecting 
such a fee. The number of invoices would be disproportionate to the amount charged to these 
companies.  This,  read  in  conjunction  with  the  general  EU  policy  on  SMEs,  leads  to  the 
conclusion  that  the  most  effective  and  efficient  approach  to  SMEs  seems  to  be  the 
to 
exemption/reduction  of 
pharmacovigilance activities through fees would thus be overall proportionate to their share of 
the market.   

companies.  The  SMEs  overall 

contribution 

these 

Further mitigating measures for SMEs 

Incentive measures have been already introduced in the past in order to alleviate the burden 
on  SMEs  and  soften  the  impact  on  smaller  companies.  All  SMEs  in  pharmaceutical  sector 
have  already  access  to  and  can  benefit  from  these  measures.  This  is  also  the  case  for  those 
companies  that  will  be  directly  influenced by  the  pharmacovigilance  activities  of  the  EMA. 
Some measures are outlined below: 

SME office 

The  SME  office  of  the  EMA  provides  information  on  companies  with  SME  status  that  are 
registered with the European Medicines Agency. The office was created in consultation with 
SME stakeholders with the objectives (1) to facilitate and promote interaction, partnering and 
networking  between  SMEs;  (2)  to  increase  information  available  to  SMEs  and  their 
stakeholders;  (3)  to  provide  a  source  of  information  for  European  Union  (EU)  institutions, 
agencies and Member States. 

EVWEB 

The  EudraVigilance  system  provides  a  web  based  tool  to  allow  for  a  manual  safety  and 
acknowledgement message creation as well as generation of medicinal product reports via a 
web  interface,  called  EVWEB.  It  is  specifically  designed  for  SMEs  and  non-commercial 
sponsors,  which do not  have a fully compliant pharmacovigilance system and/or  electronic 
transfer gateway in place. As such it provides the necessary tools to allow SMEs to perform 
secure electronic reporting to the EMA. 

EN 

57 

   EN 

 
 
 
 
 
 
 
The companies are required to undertake and pass EudraVigilance training , which is held at 
the  EMA  every  month  and  at  various  venues  around  the  EEA.  There  is  a  fee  reduction 
available to SMEs participating in these training sessions. Online materials are also available. 
Alternatively, SMEs may subcontract the electronic transmission of ADRs. 

EN 

58 

   EN 

 
 
 
 
ANNEX  6  –  PROVISIONS  OF  THE  2010  PHARMACOVIGILANCE 

LEGISLATION RELATING TO FEES 

Article 67of the Regulation: 

‘The  Agency’s  revenue  shall  consist  of  a  contribution  from  the  Union  and  fees  paid  by 
undertakings  for  obtaining  and  maintaining  Union  marketing  authorisations  and  for  other 
services provided by the Agency, or by the coordination group as regards the fulfilment of its 
tasks in accordance with Articles 107c, 107e, 107g, 107k and 107q of Directive 2001/83/EC.’ 
(new Article 67(3)) 

‘Activities relating to pharmacovigilance, to the operation of  communications networks  and 
to  market  surveillance  shall  be  under  the  permanent  control  of  the  Management  Board  in 
order to guarantee the independence of the Agency. This shall not preclude the Agency from 
charging  fees  to  marketing  authorisation  holders  for  performing  these  activities  by  the 
Agency on the condition that its independence is strictly guaranteed.’ (new Article 67(4)) 

A similar wording to Article 67(2) above is included in the Directive 2010/84: 

Article 105 

"The management of funds intended for activities connected with pharmacovigilance, the 
operation of communication networks and market surveillance shall be under the permanent 
control of the national competent authorities in order to guarantee their independence in the 
performance of those pharmacovigilance activities.  

The first paragraph shall not preclude the national competent authorities from charging fees 
to marketing authorisation holders for performing those activities by the national competent 
authorities  on  the  condition  that  their  independence  in  the  performance  of  those 
pharmacovigilance activities is strictly guaranteed." 

The following recitals of Regulation (EU) No 1235/2010 confirm that the legislator had the 
intention  that  fees  will  now  become  the  major  source  of  revenue  for  financing  the 
pharmacovigilance  activities  of  the  EMA  and  the  scientific  assessment  conducted  by  the 
Pharmacovigilance Risk Assessment Committee (PRAC) or the coordination group for human 
medicinal products (CMDh): 

(13) In order to protect public health, the pharmacovigilance activities of the Agency should 
be  adequately  funded.  It  should  be  ensured  that  adequate  funding  is  possible  for 
pharmacovigilance  activities  by  empowering  the  Agency  to  charge  fees  to  marketing 
authorisation holders. However, the management of those collected funds should be under the 
permanent control of the Management Board in order to guarantee the independence of the 
Agency.  

(14) To ensure the highest levels of expertise and the functioning of the Pharmacovigilance 
Risk Assessment Committee, rapporteurs providing assessments for Union pharmacovigilance 

EN 

59 

   EN 

 
 
 
 
 
procedures, periodic safety update reports, post-authorisation safety study protocols and risk 
management systems should receive payment through the Agency.  

(15) Therefore, the Agency should be empowered to charge fees in return for performing the 
activities  of  the  coordination  group  within  the  Union  system  of  pharmacovigilance,  as 
provided  for  in  Directive  2001/83/EC,  and  the  rapporteurs  within  the  coordination  group 
should, in turn, be paid by the Agency.  

Also  an  equivalent  recital  to  number  (13)  of  the  Regulation  cited  above  is  included  in  the 
Directive 2010/84: 

(30) In order to protect public health, the pharmacovigilance activities of national competent 
authorities  should  be  adequately  funded.  It  should  be  ensured  that  adequate  funding  is 
possible for pharmacovigilance activities  by  empowering  the national competent  authorities 
to  charge  fees  to  marketing  authorisation  holders.  However,  the  management  of  those 
collected funds should be under the permanent control of the national competent authorities 
in  order  to  guarantee  their  independence  in  the  performance  of  those  pharmacovigilance 
activities.  

EN 

60 

   EN 

 
 
 
 
  
ANNEX 7 – ASSESSMENT CRITERIA AND THE IMPACT OF INDIVIDUAL OPTIONS 

Stakeholder / criteria 

Option 1 

Option 2  

Option 3  

Option 4  

Assessment  

EMA / EC 

Balanced 
rapporteurship 

distribution 

of 

Impossible 
achieve 

to 

Neutral  to  positive  (in  all 
options, rapporteurs would 
be  remunerated  according 
to  a  fixed  scale  based  on 
average  estimated  costs 
and 
per 
workload 
procedure)  

Neutral  to  positive  (in  all 
options, rapporteurs would 
be  remunerated  according 
to  a  fixed  scale  based  on 
average  estimated  costs 
and 
per 
workload 
procedure) 

Neutral  to  positive  (in  all 
options, rapporteurs would 
be  remunerated  according 
to  a  fixed  scale  based  on 
average  estimated  costs 
and 
per 
workload 
procedure) 

Image / perception (reputation) 

Perception of failure 
to act 

Loss of credibility  

Although  the  annual  fee 
revenue  would  be  on 
average 
cost-based, 
individual  fees  could  be 
as  non-cost-
perceived 
based in some cases. 

Neutral  with 
possible 
residual risk with regard to 
the flat fee. 

Neutral  with 
possible 
residual risk with regard to 
companies  having  to  pay 
for  activities  that  are  not 
the 
related 
directly 
service provided to them. 

to 

Employment (workload) 

Impossible 
measure 

to 

Depending on the 
mechanism of charging the 
fee, the effect on workload 
for EMA should not be 
significant. This is mainly 
because it is intended that 

on 

the 
Depending 
mechanism of charging the 
flat  fee  component, 
the 
effect  on  workload  for 
EMA  should  be  moderate 
the 
mainly  because  of 

The effect on the workload 
for  EMA  should  be  from 
to  significant, 
moderate 
the 
e.g.  depending  on 
number 
procedures 
of 
occurring each year. 

EN 

61 

EN 

 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Stakeholder / criteria 

Option 1 

Option 2  

Option 3  

Option 4  

Assessment  

Simplification 

Impossible 
achieve 

to 

the invoicing would be 
automated. The EMA 
estimates that 
administrative costs 
involved would be 
negligible. 

The level of simplification 
for EMA would depend on 
the mechanism of charging 
the 
fee.  An  automated 
invoicing  would  be  an 
important simplification. 

intended 
automated 
invoicing  (as  under  option 
2).  However,  the  effect  on 
the  workload  for  charging 
the 
fee 
procedural 
component  could  be  from 
to  significant, 
moderate 
the 
e.g.  depending  on 
number 
procedures 
of 
occurring each year. 

The level of simplification 
for EMA would depend on 
the mechanism of charging 
the flat fee. The automated 
invoicing  for  the  flat  fee 
component  would  be  an 
important 
simplification. 
However,  the  invoicing  of 
the 
fee 
procedural 
component cannot be fully 
automated.  This  option  is 
therefore  less  simple  than 
options 2 and 4 

this 

Yes: fees charged only per 
procedure.  Although  the 
invoicing  of 
fee 
cannot be fully automated, 
are 
significantly 
there 
fewer 
and 
transactions 
invoiced  parties  compared 
to options 2 and 3.  

Clarity  and  transparency  of  the 
system 

Impossible 
achieve 

to 

Such  a  system  could  be 
clear  but  not  entirely 
transparent. 

transparent 

More 
option  2  because 
procedure-based 

than 
the 
fee 

The elimination of the flat 
this 
fee  could 
option  being  perceived  as 

lead 

to 

EN 

62 

EN 

 
  
 
 
 
 
 
 
 
Stakeholder / criteria 

Option 1 

Option 2  

Option 3  

Option 4  

Assessment  

Efficiency 
tasks 

/  proportionality 

to 

Impossible 
achieve 

to 

Efficiency  would  depend 
the  mechanism  of 
on 
fee.  
the 
charging 
invoicing 
Automated 
would 
to 
efficiency.  Proportionality 
would  be  achieved  on  a 
global  level,  but  could  be 
questionable 
an 
individual level. 

contribute 

on 

Manageability of the system 

Impossible 
achieve 

to 

Depends on the 
mechanism of charging the 
fee. Automated invoicing 
would improve the 
manageability but this 
positive effect might be 
undermined by possible 
debt arrears. 

component  is  paid  only 
when 
procedure 
occurs. 

the 

flat 

Efficiency  would  depend 
the  mechanism  of 
on 
fee.  
the 
charging 
Proportionality  would  be 
increased 
to 
option  2  in  respect  of  the 
fee 
procedure-based 
component. 

compared 

on 

fee 

fee. 

Depends 
the 
mechanism of charging the 
flat 
  Automated 
invoicing  would  improve 
the  manageability  of  the 
flat 
component, 
however  the  invoicing  of 
the 
fee 
procedure 
component cannot be fully 
automated.  This  option 
would be more complex to 
to 
manage 

compared 

more 
than 
transparent 
option  3.  This  effect  may 
be  offset  by  the  higher 
level of fees. 

on 

Depending 
the 
mechanism  of  charging 
the flat fee, the elimination 
of  such  a  flat  fee  could 
lead  to  more  efficiency  as 
compared to option 3. 

compared 

This  option  would  be  less 
complex 
to 
option  3.  The  complexity 
will depend largely on the 
number  of  procedures. 
Invoicing  will  not  be 
completely  automated  but 
there  will 
fewer 
transactions  and  invoiced 
parties  annually  compared 
to option 2.  

be 

EN 

63 

EN 

 
  
 
 
 
 
 
 
 
 
 
 
Stakeholder / criteria 

Option 1 

Option 2  

Option 3  

Option 4  

Assessment  

Continuity of operation / service 

Impossible 
achieve 

to 

on 

Depends 
the 
mechanism  of  charging:  
rapporteurs  would  have  to 
be 
irrespective 
whether  invoiced  fees  are 
cashed.  

paid 

Sufficient funding 

Impossible 
achieve 

to 

increase 

Furthermore, 
adjustment 
to  the  actual  cost,  i.e.  for 
in  Referral 
an 
activities, 
be 
would 
difficult  to  achieve  on  an 
yearly basis.  

This  criterion  would  be 
met  on  an  average  annual 
level, but difficulties might 
the  volume  of 
arise 
procedures 
rises 
significantly. 

if 

options 2 and 4.  

to 

Payment 
rapporteurs 
would  be  more  easily 
linked  to  the  procedure-
based  fees,  even  though 
this  payment  does  not 
necessarily  occur  after  the 
fee has been cashed. 

to 

Payment 
rapporteurs 
would  be  more  easily 
linked  to  the  procedure-
based  fees,  even  though 
this  payment  does  not 
necessarily  occur  after  the 
fee has been cashed. 

Both  procedure-based  and 
other  activities  would  be 
funded in a timely manner 
(for  other  activities,  the 
mechanism of charging the 
flat 
fee  could  have  a 
bearing). 

fund 

of 
of 

fees 
the  entire 

Procedure-based 
would 
pharmacovigilance 
EMA.  
activities 
Regularity 
PSUR 
assessment  would  have  a 
positive  effect  on 
the 
funding  of  non-procedure 
activities of EMA, but this 
positive  effect  might  be 
lower 
undermined 
activity  levels  for  PASS 
and PhV Referrals. 

by 

EN 

64 

EN 

 
  
 
 
 
 
 
 
Stakeholder / criteria 

Option 1 

Option 2  

Option 3  

Option 4  

Assessment  

Cost based fees 

Impossible 
achieve 

to 

Yes  on  annual  level,  not 
on individual level. 

Service based fees  

Impossible 
achieve 

to 

the  fee  would  be 
the 
the 

No: 
from 
disconnected 
actual  provision  of 
service. 

Yes  for  procedure-based 
fees.  Flat  fee:  yes  on 
annual 
not 
necessarily  on  individual 
level. 

level, 

Yes  for  procedure-based 
fees.  Flat  fee:  yes  on 
annual 
not 
necessarily  on  individual 
level. 

level, 

Less  than  option  3  due  to 
distribution  of  the  non-
procedure  activities  costs 
to procedure-based fees.  

Less  than  option  3  due  to 
distribution  of  the  non-
procedure activities cost to 
procedure-based fees. 

Administrative 
administrative costs 

burden 

/ 

n.a. 

on 

reduce 

Depends 
the 
mechanism  of  charging. 
invoicing 
Automated 
would 
the 
administrative  burden  and 
costs.  The  EMA  estimates 
that  administrative  costs 
involved 
be 
negligible. 

would 

Fully  automated  invoicing 
is not envisaged, however, 
the  administrative  burden 
will largely depend on the 
number  of  procedures  and 
number  of  MAHs  and 
products  involved  in  each 
Lower 
procedure. 
administrative 
burden 
compared to option 3. 

flat 

reduce 

invoicing 
Automated 
would 
the 
administrative  burden  and 
costs 
fee 
the 
for 
component.  As 
regards 
procedure-based fees, fully 
automated invoicing is not 
envisaged,  however, 
the 
administrative  burden  will 
largely  depend  on 
the 
number  of  procedures  and 
the number of transactions 
parties 
and 
each 
involved 
procedure. 
Therefore, 
administrative 
higher 

invoiced 
in 

EN 

65 

EN 

 
  
 
 
 
 
 
 
 
Stakeholder / criteria 

Option 1 

Option 2  

Option 3  

Option 4  

Assessment  

Pharmaceutical industry (MAH) 

Cost based fees 

Impossible 
achieve 

to 

burden compared to option 
2. 

Yes  for  procedure-based 
fees.  Flat  fee:  yes  on 
annual 
not 
necessarily  on  individual 
level. 

level, 

Less  than  option  3  due  to 
the distribution of the non-
procedure activities cost to 
fees 
procedure-based 
leading  to  a  risk  to  be 
perceived  as  unfair  as 
companies  not  paying  the 
fee  during  a  given  year 
could  nevertheless  benefit 
from the system.  

by 

Individual  fees  might  be 
perceived 
some 
industry  stakeholders  as 
non-cost-based. This is the 
case 
for 
in  particular 
MAHs  that  do  not  expect 
little) 
any 
involvement 
the  EU 
procedures,  even  though 
they  might  benefit  from 
the system. 

very 
in 

(or 

Service based fees  

Impossible 
achieve 

to 

the  fee  would  be 
the 
the 

No: 
disconnected 
from 
actual  provision  of 
service. 

Yes  for  procedure-based 
fees.  Flat  fee:  yes  on 
not 
annual 
necessarily  on  individual 
level. 

level, 

cost 

Yes,  with  distribution  of 
non-procedure 
the 
to 
activities 
procedure-based 
fees. 
However,  the  fees  under 
this 
less 
service-based  than  under 
option 3. 

option 

are 

Proportionality of work / fee 

Impossible 
achieve 

to 

On an individual level, this 
be 
criterion 
perceived as not met in all 

would 

Yes  for  procedure-based 
they  are  cost-
fees,  as 
based.  Flat  fee:  yes  on 

Yes,  with  a  proportionate 
distribution  of  the  cost  of 
related 
non-procedure 

EN 

66 

EN 

 
  
 
 
 
 
 
 
 
 
 
 
 
 
Stakeholder / criteria 

Option 1 

Option 2  

Option 3  

Option 4  

Assessment  

(not 

cases 
all 
substances/products  bear 
the  same  risk  and  /  or 
require the same work). 

level, 

annual 
not 
necessarily  on  individual 
level. Compared to options 
2  and  4,  this  is,  however, 
the  most  proportionate 
option. 

activities. However, this is 
than 
less  proportionate 
option 
but  more 
3, 
proportionate  than  option 
2. 

Transparency 
system 

/  clarity  of 

the 

Impossible 
achieve 

to 

system  would  be 
The 
perceived  as  clear  but  not 
fully transparent. 

for 

transparent 

than 
More 
option  2,  as 
the 
procedure-based  fees,  the 
fee 
the 
is  paid  when 
procedure  occurs.  Because 
of 
fee,  also 
the 
companies 
that  are  not 
involved in the procedures 
would  finance  the  non-
procedure 
related 
pharmacovigilance costs. 

flat 

to 

lead 

The elimination of the flat 
fee  could 
this 
option  being  perceived  as 
more 
than 
transparent 
option  3.  However,  the 
general  EMA  costs  (i.e. 
not  linked  to  procedures) 
would  be  distributed  only 
that 
amongst  MAHs 
participate 
the  EU 
in 
procedures in a given year. 

Fairness 

Impossible 
achieve 

to 

Fairer  than  option  2,  save 
the  flat  fee  that  might  still 
raise the same concern. 

The  system  would  not  be 
perceived  as  fair  by  all 
MAHs,  especially 
those 
whose  products  have  a 
safety 
well-established 
profile  and  would 
thus 
normally  be  less  involved 
in the EU procedures. 

Yes,  with  a  proportionate 
distribution  of  the  cost  of 
non-procedure 
related 
this  could  be 
activities 
considered 
acceptable. 
However, 
those  MAHs 
that  are  not  subject  to  any 
EU  procedures  would  not 
contribute to the financing 

EN 

67 

EN 

 
  
 
 
 
 
 
 
 
Stakeholder / criteria 

Option 1 

Option 2  

Option 3  

Option 4  

Assessment  

Non-duplication  of  fees  at  EU/ 
national level 

n.a. 

Simplification 
administrative burden 

/ 

reduction  of 

Impossible 
achieve 

to 

EN 

This  option  presents  the 
most  detailed  fee  grid, 
facilitate 
which  would 
comparison  with  national 
fees.  The  flat  fee  would 
cover  PhV  activities  that 
are  carried  out  only  at  the 
level of the EMA.. 

MAHs that are involved in 
procedures  would  have  to 
pay both when a procedure 
occurs  and  on  a  yearly 
basis 
fee. 
the 
However,  MAHs  that  are 

flat 

for 

The  activities  for  which 
EMA  is  charging  and  the 
corresponding costs should 
be 
to 
clearly  defined 
enable  the  MAH  to  verify 
that  they  are  not  double-
However, 
charged. 
compared 
to  procedural 
fees,  there  is  a  higher  risk 
of 
of 
perception 
duplicative charging. 

A  single  ‘flat’  fee  would 
be  less  easy  to  take  into 
account  at  national  level 
when  adjusting  national 
fees. 

on 

the 
Depending 
mechanism  of  charging, 
this criterion is likely to be 
fulfilled  for  MAH:  one 
payment per year. 

68 

of  the  system.  Therefore, 
this  option  would  be 
considered 
fair 
compared to option 3. 

less 

The  level  of  procedure-
based 
fees  would  be 
increased  by  the  cost  of 
based 
non-procedure 
the 
activities.  However, 
procedures 
content 
of 
fees 
such 
covered  by 
would  be  known,  which 
would  enable  analysis  in 
avoiding 
duplicative 
charging at national level. 

MAHs would only have to 
pay  when  a  procedure 
occurs. This would thus be 
overall simpler than option 
3. 

EN 

 
  
 
 
 
 
 
 
Stakeholder / criteria 

Option 1 

Option 2  

Option 3  

Option 4  

Assessment  

Predictability  

NCA / MS 

Cost based fees 

Impossible 
achieve 

to 

involved 

not 
any 
procedures would only pay 
the flat fee.  

in 

The  fees  for  PhV  referrals 
and  for  PASSes  would  be 
less predictable (compared 
to the flat fee) because the 
actual  occurrence  and  the 
scope  of  such  procedures 
are not known in advance. 
more 
are 
PSURs 
predictable  due 
the 
EURD list (as explained in 
Annex 1). 

to 

Yes:  the  amount  of  the 
fees 
procedure-based 
would  be  linked  to  the 
average  cost  of  NCA 
rapporteurs. 

Yes,  a  flat-fee  would  be 
predictable for MAHs (and 
EMA)  regardless  of  the 
number  of  procedures  a 
be 
company 
and 
involved 
irrespective 
the 
mechanism of charging.  

would 
in 

of 

include 

The  calculation  of  the  fee 
the 
would 
estimated average costs for 
NCAs  rapporteurs  but  this 
link  would  not  be  visible 
at  individual  level.  NCAs 
would  be  remunerated  for 
their  average  estimated 
evaluation 
costs 
procedure. 

per 

The  fees  for  PhV  referrals 
and  for  PASSes  would  be 
less  predictable  compared 
the 
to  PSURs  because 
actual  occurrence  and  the 
scope  of  such  procedures 
predictable. 
are 
more 
PSURs 
predictable. 

less 

are 

entirely: 

the 
Not 
fees 
procedure-based 
would 
an 
'overhead'  for  the  cost  of 
non-procedure 
related 
activities. 

include 

EN 

69 

EN 

 
  
 
 
 
 
 
 
 
 
 
 
 
 
Stakeholder / criteria 

Option 1 

Option 2  

Option 3  

Option 4  

Assessment  

Coverage  of  the  NCA  work    / 
adequate 
of 
assessment work of rapporteurs 

remuneration 

Impossible 
achieve 

to 

Expertise 
enhancement, sharing 

development, 

n.a. 

Yes: all rapporteurs would 
be  remunerated  according 
to  a  fixed  scale,  based  on 
average estimated cost and 
workload per procedure. 

Yes: all rapporteurs would 
be  remunerated  according 
to  a  fixed  scale,  based  on 
average estimated cost and 
workload per procedure. 

Yes: all rapporteurs would 
be  remunerated  according 
to  a  fixed  scale,  based  on 
average estimated cost and 
workload per procedure. 

Neutral:  all 
rapporteurs 
remunerated 
would  be 
according  to  a  fixed  scale, 
average 
based 
on 
and 
estimated 
workload per procedure. 

cost 

Neutral:  all 
rapporteurs 
remunerated 
would  be 
according  to  a  fixed  scale, 
average 
based 
on 
and 
estimated 
workload per procedure. 

cost 

Neutral:  all 
rapporteurs 
remunerated 
would  be 
according to a fixed scale, 
average 
based 
on 
and 
estimated 
workload per procedure. 

cost 

EN 

70 

EN 

 
  
 
 
 
 
 
 
 
 
 
ANNEX 8 – WIDER CONTEXT OF THE INITIATIVE 

European Medicines Agency (EMA) 

The EMA operates through a network of NCAs and coordinates the scientific resources made 
available by them, thereby ensuring the evaluation and supervision of medicinal products. The 
EMA is an EU body with its own legal personality and is one of the few EU Agencies which are 
fee-earning. The revenue of the EMA consists of an EU contribution (approximately 20%) and 
fees from industry (appr. 80%) charged to MAHs for obtaining and maintaining EU marketing 
authorisations.  

At  the  start  of  year  N-1,  EMA  prepares  a  preliminary  draft  budget  which  is  adopted  by  its 
Management  Board  usually  at  its  March  meeting  of  N-1.    The  final  budget  of  EMA  is 
prepared at the end of year N-1 and it takes account of the budget of the European Union, as 
proposed for adoption by the Budgetary Authority. After the adoption of the budget and the 
establishment plan for year N by the EMA Management Board, a copy is sent to the European 
Parliament.    The  annual  budget  is  published  on  the  external  website  of  the  EMA  and  a 
summary version is published in the Official Journal of the European Union. 

The EMA budget for 2012 was €223,5 million of which €183 million stems from fees and €39 
million from EU contributions. Over the last 10 years the proportion of the revenue from fees 
has increased whereas the proportion from the EU contribution has decreased.  

Marketing Authorisation procedures 

Given that it is proposed that EMA could also charge pharmacovigilance fees for non-centrally 
authorised  medicinal  products,  a  brief  description  of  the  system  of  authorisation  of  medicinal 
products in the EU is given below.  

Medicinal  products  authorised  by  the  Commission  in  accordance  with  the  procedure  under 
Regulation  No  726/200436  (the  so-called  “centralised  procedure”)  are  referred  to  as  'centrally 
authorised products' ('CAPs'). A marketing authorisation (MA) can also be issued by an 'NCA' 
for its own territory (pure national marketing authorisation). As regards MAs in several Member 
States (MSs), two authorisation procedures exist:  
(i) the mutual recognition procedure ('MRP') where a medicinal product is first authorised in one 
MS  under  the  national  procedure,  and  in  the  case  where  subsequent  applications  for  MAs  are 
filed in other MS, the latter agree to recognise the validity of the first MA; and  
(ii) the decentralised procedure ('DCP') where the MA applications are submitted simultaneously 
in  different  MS  and  for  which  one  MS  acts  as  reference  MS  (carrying  out  the  scientific 
evaluation).  
Products  authorised  by  the  NCAs  under  any  of  the  latter  three  procedures  (i.e.  purely  national 
authorisations  and  authorisations  under  the  MRP  or  DRP)  are  hereinafter  referred  to  jointly  as 
'non-centrally  authorised  products'  ('non-CAPs').  After  the  granting  of  the  MA,  the  MAH  will 
benefit from data exclusivity for a period of at least 8 years (during which generics cannot enter 
the market). This data exclusivity applies in parallel with provisions on patents. These rules are 
intended as incentives to originator companies for innovation. 

36 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 Agency, OJ L 136, 30.4.2004 

EN 

71 

   EN 

 
 
 
 
 
 
                                                 
The EMA is responsible for the evaluation, authorisation and supervision of medicinal product 
for  human  and  veterinary  use  in  accordance  with  the  procedures  laid  down  in  the  Regulation. 
The  EMA  currently  also  has  a  role  for  non-CAPs  in  the  context  of  referrals,  however,  such 
referrals are not subject to fees except if the referral is triggered by the MAH (which so far has 
not happened). A referral is a procedure used to resolve issues such as concerns over the safety 
of a medicine or a class of medicines or in cases of disagreements among Member States on the 
use of the medicine. The medicine, or the class of medicines, is ‘referred’ to EMA, so that it can 
make a recommendation for a harmonised position across the European Union which often leads 
to the Commission adopting a decision addressed to the Member States, reflecting the measures 
to  take  to  implement  the  recommendation.  A  referral  can  normally  be  triggered  by  the 
Commission, the Member States or the MAH. While there are different types of referrals, this IA 
(and  any  possible  legal  proposal  that  derives  from  it)  only  deals  with  pharmacovigilance 
referrals and hence fees for pharmacovigilance referrals, as only they are within the scope of the 
2010  pharmacovigilance  legislation.  Pharmacovigilance  referrals  are  typically  triggered  by  the 
MS or the Commission. 

2010 Pharmacovigilance legislation 

A major revision of the EU legislation on pharmacovigilance was introduced in 2010 through 
the adoption of  

•  Regulation  (EU)  No  1235/2010  of  the  European  Parliament  and  of  the  Council 
amending,  as  regards  pharmacovigilance  of  medicinal  products  for  human  use, 
Regulation No 726/2004 and 
 Directive  2010/84/EU  of  the  European  Parliament  and  of  the  Council  amending,  as 
regards pharmacovigilance, Directive 2001/83/EC.  

• 

The new legislation became applicable in July 2012 The changes affect CAPs and non-CAPs. 
Given that the 2010 pharmacovigilance legislation provides a greater role for EMA in the area 
of  pharmacovigilance  in  general,  i.e.  irrespective  of  how  the  medicinal  products  have  been 
authorised (therefore including both nationally and centrally authorised products), EMA will for 
the  first  time  be  able  to  charge  fees  also  for  nationally  authorised  products.  Many  NCAs 
currently charge the MAHs for pharmacovigilance activities, and hence there is also a need to 
ensure that MAHs are not charged twice for the same work. Therefore, the fees of EMA should 
be transparent in order for companies to be able to identify what pharmacovigilance activities 
the  new  fees  would  correspond  to.  It  should  also  be  borne  in  mind  that  while  the  2010 
Pharmacovigilance legislation lays down certain obligations on the MAHs, the activities of the 
regulatory  authorities  in  the  area  of  pharmacovigilance  (i.e.  detection  of  safety  signals, 
assessment of these signals and regulatory follow-up) constitute a service to the MAHs.  

The Commission's proposal of 10 December 2008 to amend the pharmacovigilance legislation 
was  accompanied  by  a  Financial  Statement37  according  to  which  all  costs  related  to  activities 
resulting from the legislative proposal are to be recuperated through fees. 

Fees Regulation and Implementing Rules 

Fees  are  currently  charged  by  the  EMA  in  accordance  with  Council  Regulation  (EC)  No 
297/95  (Fees  Regulation)38.  The  Fees  Regulation  sets  out  fees  for  CAPs  and  in  the  case  of 

37 http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=COM:2008:0664:FIN:en:PDF. 
38 OJ L 35, 15.2.1995 p.1 

EN 

72 

   EN 

 
 
 
 
 
 
 
                                                 
some  referrals  initiated  by  the  MAH  also  for  non-CAPs39.  The  Fees  Regulation  was  last 
amended in 2005. For the application of the Fees Regulation, there are Implementing Rules 
adopted by the Management Board of EMA.  
The  existing  pharmaceutical  legislation  provides  for  various  fee  incentives  for  SMEs  for 
CAPs.  

Remuneration of the MS rapporteurs 

The legislation and the Implementing Rules of the current Fees Regulation provide, inter alia, 
that  the  NCAs  acting  as  rapporteurs  or  co-rapporteurs,  i.e.  carrying  out  the  evaluation  of 
medicinal  products  and  the  subsequent  follow-up,  are  remunerated  by  the  EMA  for  their 
work. It may be noted that there is currently also some work carried out by the rapporteurs/co-
rapporteurs  for  which  they  are  not  remunerated.  For  the  evaluation  of  an  initial  marketing 
authorisation  under  the  centralised  procedure  (for  which  the  current  fee  is  approximately 
270.000€),  the  rapporteurs/co-rapporteurs  receiv e  50%  of  the  fee  charged  by  EMA.  The 
European Court of Auditors, in its annual reports on the EMA, has repeatedly been criticising 
that these payments to the MS are not cost-based. Recently, also the European Parliament has 
raised criticism on this point in the context of the discharge procedure. Hence, the EMA has 
been  requested  to  report  to  the  EP  on  progress  made  in  this  area  by  May  2013.  This  is 
currently in the competence of the Management Board, as the level of remuneration of MS is 
laid down in the Implementing Rules of the existing Fees regulation. 

Legal  base 
Pharmacovigilance legislation 

to  charge 

fees 

for  pharmacovigilance  activities  under 

the  2010 

Whereas  the  previous  (2004)  wording  of  Article  67(4)  of  the  Regulation  provided  that 
pharmacovigilance activities are to be publicly funded, the revised Regulation (as amended by 
the 2010 pharmacovigilance legislation) provides that industry is to be charged fees by EMA 
for  the  conduct  of  pharmacovigilance  activities.  In  order  to  enable  EMA  to  charge  fees  for 
pharmacovigilance, there is a need for a legal instrument. 

39 In practice, however, this fee is never applied. 

EN 

73 

   EN 

 
 
 
 
 
 
 
                                                 
ANNEX 9 – ASSIGNING IMPORTANCE TO THE ASSESSMENT CRITERIA  
Analytical hierarchy process technique was used in order to assign weights to each of the four 
criteria used in the assessment in order to reflect and formalize its relative importance. As a 
first  step,  a  pairwise  comparison  of  the  criteria  was  made  through  a  series  of  judgments  in 
order  to  construct  a  ratio  scale.  The  comparison  values  are  outlined  in  Table  3  and  were 
defined as follows: 

1  
2 
3 
4 
5 

Both criteria are of equal importance 
Criterion A is slightly more important than criterion B 
Criterion A is strongly more important than criterion B 
Criterion A is very strongly more important than criterion B 
Criterion A is absolutely more important than criterion B 

Table 3: Comparison values 
                               B 
               A 

transparency 

stability / 
predictability 

simplicity 

fairness / 
proportionality 

Transparency 

stability / 
predictability 
Simplicity 

fairness / 
proportionality 

1 

1/3 

1/4 

2 

3 

1 

1/2 

3 

4 

2 

1 

4 

1/2 

1/3 

1/4 

1 

A simple calculation was made in Table 4 to determine the overall weight that we assign to 
each criterion and that will be subsequently used for making the decision on preferred option. 
This  weight  is  between  0  and  1  and  the  total  weight  adds  up  to  1.  The  overall  weighting 
column  establishes  priorities  among  the  criteria  used.  The  results  suggest  that  45  %  of  the 
objective weight is on fairness and proportionality, 32 % on transparency, 14 % on stability 
and predictability and 9 % on simplicity.    

Table 4: Relative weighting of criteria 

transparency 

stability / 
predictability 

simplicity 

fairness / 
proportionality 

Overall 
Weighting

transparency 
stability / 
predictability 
simplicity 
fairness / 
proportionality 

0,279 

0,400 

0,364 

0,240 

0,093 
0,070 

0,558 
1 

0,133 
0,067 

0,400 
1 

0,182 
0,091 

0,364 
1 

0,160 
0,120 

0,480 
1 

32% 

14% 
9% 

45% 
100% 

EN 

74 

   EN