The document outlines the structure and importance of pharmacovigilance, emphasizing the need for monitoring drug safety and the organization of associated processes at both national and European levels. It details the definitions of adverse drug events and serious side effects, historical cases influencing drug safety practices, and the role of various stakeholders in reporting and evaluating drug-related risks. Additionally, it discusses the regulatory framework, including requirements for periodic safety update reports and actions to be taken based on findings.

2. • Introduction of pharmacovigilance
• Drug safety in practice
• Need for monitoring the safety of drugs
• Organisation of pharmacovigilance

3. • Have knowledge of the definition of
pharmacovigilance
• What is a “serious” side effect, according to
the formal definition.
• Peruse the history of pharmacovigilance and
a number of side effects that have played a
role.
• Knowledge on how safety of medicines in the
Netherlands and Europe are organised

4.  The science and activities relating to the
detection, assessment, understanding and
prevention of adverse drug effects or any
other drug related problem

5.  A response to a drug which is noxious and
unintended, and which occurs at doses
normally used in man for prophylaxis,
diagnosis, therapy or for the modifications of
physiological function

7.  ADE: Adverse Drug Event
› Medical occurrence temporally associated with the use of a medicinal
product, but not necessarily causally related
› Not consistent with applicable product information or characteristics of
drug
 AE: Adverse Event
› Medical occurence which is not necessarily causally related to the use of a
drug, and might rely on coincidence
 Definition WHO
› Response of drug action in a person, resulting in experienced harm

8.  A medical event that gives rise to one or more of the
following
› Death
› Life-threatening situations
› Hospitalization or prolongation thereof
› Permanent incapacity or disability
› Birth defects
› Other medically important conditions

11.  Five years between first victim and the
withdrawal of thalidomide from the market
 Establishment of Medicines Evaluation Boards
worldwide
 Establishment of spontaneous reporting
centers to identify potential adverse drug
reaction in an early stage

12.  Drug is back on the market and is now used
for the treatment of, for example
- Leprosy
- HIV / AIDS complications
- Multiple myeloma (multiple myeloma)
 New cases of congenital malformations,
despite precautionary measures

13.  Synthetic oestrogen for the prevention of
miscarriages
- On the Dutch market from 1947-1976
- Warning NTvG 1972
- Ministry of Health issued warning not to use
DES anymore in 1974
 In children of mothers who used DES there
is an increasred risk of
- cervical cancer (Clear Cell Adenocarcinoma)
- deviations in the shape of the uterus

16.  No children
 No elderly
 Not pregnant
 Little or no comorbidity
 Little or no use concomitant medications
 Limited numbers
 ADRs with long time onset hard to detect

18.  Extensive research before drug reaches the
market
 At the time of market authorization has
balance safety / efficacy good
 In post-marketing (Phase IV) more knowledge
open approach: spontaneous reporting
when needed additional studies
 Combination of knowledge is used to monitor
balance safety / efficacy

19.  Medicines Evaluation Board
 Netherlands Pharmacovigilance centre
 Healthcare professionals and patients
 Marketing Authorization Holders
 Inspectorate of health
 EMA
 WHO

20.  Healthcare professionals should immediately
report any suspected serious adverse
reactions to a body of professionals and
patient organizations as referred to in Article
76, paragraph three, and any suspected
transmission via a medicinal product of
infectious agents

21.  Signalling and Analysing as yet unknown
adverse events
- Identifying adverse events (partially from
Lareb)
- Evaluation of PSURs
 Final risk/benefit assessment
 Determine actions to be taken i.e. by
- Amendment of SmPC
- Dear Health Care Professional letter
- Suspension of withdrawal of drug

22.  Amendment Summary of product characteristics
- New update
- Warning
- Contraindication
- Mitigate indication of use
 Temporary suspension of drug
 Withdraw drug from market
 Informing medical professionals by a “Dear
Healthcare Professional Communication” (DHPC)
 Initiate additional reasearch into the safety of a
drug

23.  Monitoring safety of own products on a
continuous basis
- Spontaneous reports
- Evaluation of studies
- Literature
 Periodic Safety Update Reports
 If applicable, apply for an update in the
product information in between

24.  Overview of serious and non-serious adverse reactions
worldwide
 Frequency
- a PSUR every six months for the first two years after
being placed on the market
- during the following two years a PSUR every year
- thereafter at three-yearly intervals
- If needed more often…
 Is change in SmPC needed?

25.  Reports are forwarded to the Eudravigilance
database of the European Medicines Agency
 Registration
- National (National Authorised products)
- Central (Central Authorised products)
 Signal Detection via member states
- National level
- Central level

26.  Provide advise on safety medicinal products
authorised in the EU
 Investigation of ADRs to enable effective
assessment and management of risk during
any phase in product life cycle

27. • Evaluation of potential signals
• Provision of advice on confirmation and
quantification of risk and on regulatory
options;
• Risk management
• Monitoring regulatory action and the
outcomes
• Setting standards for procedures and
methodologies

29.  Receipt, analysis and recording of worldwide
adverse event data
 Maintenance and screening of the
international database
 Studies on WHO database
 Training courses and meetings on
pharmacovigilance

30. 1. Website EMA: central registered products
2. Website national MEB (CBG): all other products
3. KNMP - Informatorium Medicamentorum (for
pharmacists)
4. Farmacotherapeutisch Kompas (free access)
5. Website Netherlands PV centre Lareb: spontaneous
reports; not always a causal relationship!
 1 and 2 official information
 Other sources additional and interpreted information