EN    EN EN 
EN    EN  COMMISSION OF THE E UROPEAN COMMUNITIES 
Brussels, 10.12.2008 
SEC(2008) 2671 
COMMISSION STAFF WORKING DOCUMENT 
Accompanying document to the 
 
Proposal for a 
 
REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL  
 
amending, as regards pharmacovigilance of  medicinal products for human use, 
Regulation (EC) No 726/2004 laying down Co mmunity procedures for the authorisation 
and supervision of medicinal products for hu man and veterinary use and establishing a 
European Medicines Agency 
 
and the 
 
Proposal for a 
 
DIRECTIVE OF THE EUROPEAN PA RLIAMENT AND OF THE COUNCIL  
amending, as regards pharmacovigilance, Di rective 2001/83/EC on the Community code 
relating to medicinal products for human use 
   
SUMMARY OF THE IMPACT ASSESSMENT  
{COM(2008) 664 final} {COM(2008) 665 final} 
{SEC(2008) 2670} 
EN    EN 1. INTRODUCTION  
Medicines contribute considerably to the health of EU citizens. The discovery, 
development and effective use of drugs have improved many people's quality of life, reduced the length of time sp ent in hospital and saved many lives. Consumption of drugs 
is increasing, with pharmaceutical mark et value reaching €141 billion in 2006. 
Medicines can, however, also have adverse (n egative) effects. Adverse drug reactions 
(ADRs – a response to a medicine which is  noxious and unintended) present a major 
public health burden in the EU. It is estimated that 5% of all hospital admissions are due 
to an ADR, 5% of all hos pital patients suffer an ADR and ADRs are the 5
th most 
common cause of hospital death. It is estima ted that 197,000 deaths per year in the EU 
are caused by ADRs and that th e total societal cost of ADR s in the EU is €79 billion. 
Medicines regulation and particularly the system  of authorising medici nes are critical for 
ensuring that only high quality, efficacious me dicines of acceptable sa fety are allowed on 
the EU market. However, the established lim itations of drug devel opment, particularly 
the limitations of clinical trials in terms of their size, duration and controlled conditions means that some side effects will only be de tected after a medicine has been authorised 
and entered the market.  
Pharmacovigilance is the scie nce and activities relating to  the detection, assessment, 
understanding and prevention of adverse effect s of drugs and comprises: collecting and 
managing data on the safety of medicines, scrutinising at the data to detect ‘signals’ (any 
new or changing safety issues), evaluating th e data and making decisions with regard to 
safety issues, acting to protect public he alth (including regulatory action), and, 
communicating with stakeholders ab out the safety of medicines.  
Key stakeholders involved in  pharmacovigilance are:  
• patients as the users of medicines and families and carers as advisers and carers of 
patients,  
• all healthcare profession als but particularly: 
– doctors (to advise patients, pres cribe medicines and report ADRs) 
– pharmacists (to advise patients, disp ense medicines and report ADRs) 
– nurses (to advise patients, admini ster medicines and report ADRs) 
– academia (to conduct studies into the safety of medicines) 
• medicines regulators includi ng Member States National Competent Authorities 
(including regional centres),  the European Medicines Agency (EMEA) and the 
European Commission,  
• Healthcare service providers and governm ents and social insurance schemes, 
EN    EN • Pharmaceutical industry, including Mark eting Authorisation Holders (innovative, 
generic and over-the-counter medicines sect ors), manufacturers and distributers of 
medicines (comprising a wide range of co mpany sizes including a high proportion of 
small and medium-sized enterprises -SMEs). 
Of these stakeholders the cu rrent EU regulatory framework, made up principally of 
provisions in Regulation (EC) No 726/ 2004 and Directive 2001/83/EC (supported by 
implementing guidelines), place direct oblig ations on medicines regulators and the 
industry only. However, the impact of these provisions can affect indirectly all those 
listed above, particularly in terms of  the public health burden of ADRs. 
2. PROBLEM DEFINITION  
Significant weaknesses of the current EU sy stem of pharmacovigilance have been 
identified through an independent Comm ission sponsored study, extensive public 
consultation (in 2006 and ag ain in 2007) and through detailed analysis by the 
Commission services. These weaknesses include: 
• A lack of clear roles and responsibilities fo r the key responsible parties and a lack of 
clear obligations against which they pe rform their roles (re sulting in poor 
compliance); 
• Slow EU decision-making on drug safety issu es particularly for nationally authorised 
products and frequent disharmony in action taken by the Member States; 
• Low levels of transparency relating to  pharmacovigilance and relatively limited EU 
coordination of communication about the safe ty of medicines, pl us complex product 
information with poor penetration of key warnings; 
• Cumbersome oversight of co mpanies' pharmacovigilance systems by the authorities; 
• A lack of proactive and proportionate monito ring including a lack of risk management 
and structured data collecti on in the form of post auth orisation safety studies and 
duplicative reporting rules for the industry and authorities rela ting to both 15-day, 
literature and periodic ( PSUR) reporting of ADRs;  
• Lack of inclusiveness of stakeholders incl uding a lack of direct patient reporting of 
ADRs and their virtual absence from decision-making. 
Overall these weaknesses mean that limited re sources are diverted to meet complex and 
duplicative administrative requirements, ther e is an over-reliance on poor quality reactive 
data, decision-making is slow and measures to reduce risk to patients are not only 
sometimes late but frequently of limited effectiveness. Taken together these problems mean that the safety of EU citizens is not  optimally protected so that there is an 
opportunity to reduce the public he alth burden ADRs by improving EU 
pharmacovigilance. In addition, the divers ity of Member Stat e pharmacovigilance 
requirements and the disparate Member Stat e action on safety issues for nationally 
authorised products means th at the single market in pharmaceuticals is not fully 
achieved. 
EN    EN 3. OBJECTIVES  
The specific objective of the proposals is to  improve the health of EU citizens by 
strengthening and rationa lising pharmacovigilance.  
The operational objectives of the proposals can be summarised as:  
(1) Providing for clear roles and responsibilities fo r the key responsible 
parties and clear obligations agains t which they perform their roles; 
(2) Rationalising EU decision-making on drug safety issues in order to deliver 
measures that are equally and fully implemented for all relevant products 
and across the community with a view  of preventing unnecessary patient 
exposure to risks; 
(3) Strengthening medicines safety tr ansparency and communication to 
increase the understanding and trust of  patients and health professionals 
in the safety of medicines and impr ove the penetration of key warnings; 
(4) Strengthen companies' pharmacovigila nce systems, allowing companies to 
improve their systems constantly wh ile reducing administrative burden; 
(5) Ensure the proactive and proportionate  collection of high quality data 
relevant to the safety of medici nes through risk management and 
structured data collection in the form  of post authorisation safety studies, 
together with rationalised single case and periodic reporting of suspected 
adverse reactions; 
(6) Involve stakeholders in pharmacovi gilance including through direct 
patient reporting of suspected advers e reactions and inclusion of patients 
and heath-care professi onals in decision-making. 
4. POLICY OPTIONS  
Four basic policy-options were developed for the impact assessment:  
(1) No policy-change;  
(2) Deregulation;  
(3) Self-regulation, and;  
(4) Amendment to the existing Eur opean Community legislation.  
Enhanced implementation and enforcement work  within the current legal framework (i.e. 
option 1) will improve pharmacovigilance and EU public health protection and it is for 
this reason that work to improve implemen tation of the current EU pharmacovigilance 
system is an integral part of the Commission "Strategy to Better Protect Public Health by Strengthening and Rationalising EU Pharm acovigilance" announced in February 2007. 
However, the impact overall of improvement s of the current EU system will be limited 
and the step change improvement in public heal th protection can only be realised with a 
EN    EN change to EU legislation. On this basis on ly option 4 proved a rea listic way of meeting 
the objectives proposed. 
A large number of potential policy options we re highlighted by the independent study 
and by stakeholders during the first public c onsultation. The specific policy options were 
selected and modified based on an iterative  process of problem investigation, process 
understanding, expert dialogue and stakeholder consultation with options being fine-
tuned while others were exclude d during the process.  Fifteen specific policy options were 
selected on the basis that they provided th e best sum of the impacts and an overall 
coherence of the EU regulatory system. These fi fteen were included in the legal proposal.  
These are:  
• Clarification and codification of the tasks and responsibilities of involved parties and 
establish standards; 
• Establishment of a clear EMEA committee st ructure for pharmacovigilance scientific 
assessment and decision making coordinati ng activities and making recommendations 
on the safety of medici nes at the EU level; 
• Rationalising the EU pharmacovi gilance referral procedures; 
• Increasing drug safety transparency; 
• Improved EU coordination of communicati on about major new or changing safety 
issues and establishment of an EU po rtal on the safety of medicines;  
• Introduction of a new section in the Summar y of Product Characteristics and Patient 
Information Leaflet on ‘key information' with a transitional implementation period; 
• Introduction of a "Pharmacovigilance System Master File" to ensure robust but un-
bureaucratic oversight of compan ies pharmacovigilance systems; 
• Provision of a clearer legal basis for risk management plans for new and authorised 
products with safety concerns, includ ing post-authorisation safety studies; 
• Codification of guiding principles and overs ight for the conduct of non-interventional 
post-authorisation safety studies;  
• Simplification of ADR reporti ng using the EU Eudravigilance database as a central 
tool; 
• Scanning of the scientific literature by th e EMEA with a clearly defined in scope;  
• Exchange of data on medica tion errors that result in an adverse reaction including 
between the competent authorities for me dicines and those for patient safety;  
• Removal of the current rou tine requirement for industry periodic reports (PSURs) for 
low risk, old and established products; 
EN    EN • Provision of the legal basis for the new EMEA pharmacovigilance committee 
structure to require submission and coor dinate assessment of PSURs and make 
consequent recommendations  for product labelling; 
• Provision of the legal basis for patients to report suspected adverse drug reactions. 
5. ANALYSIS OF IMPACTS  
The chosen policy options were found to be  coherent with exis ting international 
harmonisation in pharmacovigilance and will  lead to further convergence with the 
systems in place or being introduced in the United States, Canada and Japan.  
The chosen policy options were  not found to have a signif icant environmental impact. 
However, the increased use of informati on technology will reduce the need for duplicate 
paper reporting and the increase in tr ansparency will allow pharmacovigilance 
assessments to be widely available though the internet. 
With regard to impact on public  health (the key social imp act) none of the chosen policy 
options have a negative impact and those with  the greatest positive impact were found to 
be: codified roles, responsibilities and st andards; fast robust EU decision-making; 
transparency and EU coordination of dr ug safety communications; improved product 
information; improved risk management incl uding high quality post- authorisation safety 
studies, data sharing on medication erro rs and work-sharing on the assessment of 
periodic reports (PSURs).  
Overall the most conservative estimate of the saving to society of the proposals is €237 
Million per year across the EU with a maximum estimate  of €2.4 Billion per year. The 
most conservative estimate of the public hea lth impact of the proposals suggested 591 
lives saved across the EU per year with a maximum estimate of 5910 lives saved per 
year. 
Currently the EU pharmaceutical industry se ctor spends an estimated €833 Million 
annually on meeting the EU regulatory re quirements for pharmacovigilance and the 
policy options proposed would redirect th e industry spend from  duplicative ADR, 
periodic, literature and system reporting to pr oactive monitoring, with higher quality data 
collection through risk management planning an d post-authorisation st udies. Overall, and 
including this redirection of spending, the p ackage of proposals will save the EU industry 
sector an estimated €145 Million per year representing 17.4% of their current EU 
spending on pharmacovigilance. 
In 2004 the EU medicines regulators employe d 317 staff in pharmacovigilance activities 
and staff numbers have increased slightly over time. The proposals will lead to costs 
incurred by the regulators w ith estimated one-off implemen tation costs of €3,9 Million 
for the EMEA and €3.0 Million across the EEA National Competent Authorities and 
ongoing annual running costs of  €10.1 Million for the EMEA and €4.6 Million across the 
EEA National Competent Authorities. The propos als explicitly foresee industry fees to 
cover these pharmacovigilance costs and these fees are included in the calculations of 
industry costs which revealed 17.4% overall i ndustry savings. It should be noted that 
these figures will not necessarily result in direct fee increases as, at least for the EMEA, fee income is currently in surplus. 
EN    EN 6. CONCLUSION  
This impact assessment has shown that increasing the clarity, efficiency and quality of 
the EU system of pharmacovigilance, thr ough amendments to the existing EU legal 
framework, presents a win win situation with major public health improvements of at 
least 591 lives and €237 Million of public health burden saved per year across the EU and overall cost savings of €145 Million per year to the EU industry sector.