The WHO Medicines Safety Programme focuses on pharmacovigilance and risk minimization for biological products, responding to the historical context of drug safety challenges like thalidomide. It emphasizes the need for systematic monitoring of adverse drug reactions, particularly for biotherapeutics and biosimilars, and outlines strategies for strengthening national pharmacovigilance systems. The document further highlights the importance of collaboration, training, and the engagement of both governments and private industries in creating effective pharmacovigilance frameworks.

1. WHO Medicines Safety Programme:
Pharmacovigilance and risk minimization programs
for biological products
Dr Shanthi Pal
Medicines Safety Programme Manager
Essential Medicines and Health Products, WHO
pals@who.int
pvsupport@who.int

2. Birth of modern pharmacovigilance
Thalidomide – Phocomelia 1961

3. 16th World Health Assembly 1963
Assembly Resolution 16.36 - Clinical and
Pharmacological Evaluation of Drugs
INVITES Member States to arrange for a systematic
collection of information on serious adverse drug
reactions observed during the development of a drug
and, in particular, after its release for general use.

4. WHO Programme for International
Drug Monitoring
WHO-HQ
Geneva
WHO-HQ
Geneva
UMC
WHO-CC
Uppsala
UMC
WHO-CC
Uppsala
National
Centres
UMC-A
WHO-CC
Accra
UMC-A
WHO-CC
Accra
WHO-CC
Rabat
WHO-CC
Rabat
WHO-CC
Oslo
ATC DDD
WHO-CC
Oslo
ATC DDD

5. Pharmacovigilance in WHO
1. Exchange of Information
2. Policies, guidelines, normative activities
3. Country support
4. Collaborations
5. Resource mobilisation

6. Advisory Committee on Safety of Medicinal
Products (ACSoMP)
The Advisory Committee on Safety of Medicinal Products shall
provide advice on pharmacovigilance policy and issues
related to the safety and effectiveness of medicinal products
to the relevant Assistant Director-General in WHO and
through him / her
to the Collaborating Centres for the Medicines Safety
Programme, and
to the Member States of WHO

7. What defines it
The WHO PV strategy

8. Understanding what's available and
what's needed in countries

9. Challenges to Pharmacovigilance

10. Type of assistance needed

11. WHO International Drug Monitoring Programme
Situation 1990

12. WHO International Drug Monitoring Programme
Situation 2012

13. WHO strategy

14. Concept of generics
Patent expiry of medicines enables
Generics
Cost savings because no need to invest in further
human trials for safety and efficacy
Can use data from investigations with innovator
products
More patients receive treatment
Further investment in new medicines

15. Global Fund HIV/AIDS Coverage
After 9 Rounds of proposals
0 5,0002,500
Kilometers
´

16. Traditional chemical medicines
relatively small
Stable molecules
No need to repeat large-scale human trials
Safety monitoring is needed nevertheless
Used in 'other' environments & populations: LMIC
 Comorbidities, nutritional effects, genetic differences
Long-term effects

17. Pharmacovigilance in Global Fund grants
A 2010 analysis of Grant applications in the Global FundA 2010 analysis of Grant applications in the Global Fund
database (R4 to R9)database (R4 to R9)
Is PV mentioned?
Does it set out to establish min PV requirements?
 431 individual Global Fund Proposals
31% had “acceptable reference to PV''
Interviews: even if mentioned, PV not implemented in
practice
(Ref: Unpublished data, Pal, Xueref et al; 2010)

18. Joint WHO/Global Fund
pharmacovigilance strategy
Establish basic functions and minimum requirements of
national pharmacovigilance system
Minimum PV requirements
pharmacovigilance toolkit to support training and
development
www.PVToolkit.org
Strong wording in Round 10 requesting countries to include
PV

19. Biotherapeutics
Generally large, complex molecules
produced from living cells using biotechnology
can pose rare but serious risks of unwanted immune
responses
Require extensive testing and risk management
planning

20. Similar biotherapeutic products (SBPs)
Copies or 'generic' versions of biotherapeutic
products (SBP)
Are not exact copies of innovator products
Due to manufacturing process
Unlike other generics, can't rely on data for / from
innovator products
Need sufficient proof of similarity to innovator
product (both preclinical laboratory testing and
clinical trials
Risk management plans are also essential

21. Guidance from WHO
Developed in 2009
Published in 2010
Based on EMA guidelines of 2006

22. Pharmacovigilance of SBPs
Manufacturer required to submit
Safety specification and PV plan at the time of
submission for approval
Safety specification should describe important
identified or potential safety risks for RBP, the
substance class and / or any that are specifc for the SBP
 Risk minimization activities may be needed : education
material for patients / HCP etc

23. Post approval activities for SBPs
Due to potential of SBPs to provoke immune
reactions
manufacturers to undertake post marketing
surveillance to the same standards as RBP MAH
Pharmacovigilance plan should include
Safety monitoring as required of corresponding RBP
Safety monitoring for additional risks identified
SBP manufacturers required to have
PV systems in place at approval
Qualified PV personnel
means to report to NRAs where the reactions occur

24. Traceability of Adverse events
AEs may be product specific
Critical information to assign AEs with specific BPs
ADR report for any BP to include
INN
Proprietary or brand name
Manufacturer's name
Lot number
Country of origin

25. Number of reports/million inhabitants/year
Reporting last 5 years

26. Reports on Monoclonal antibodies (MABs) in
WHO database (out of 8 million Individual Case
Safety Reports, ICSRs)
Total
ICSR 356787
ICSRs with INN, trade
names, indications
285327

27. Reports by country (top 10)

28. Top 5 ADRs with MAB in WHO
database
MedDRA_PT_name Number_of_Reports
Fatigue 18208
Drug ineffective 15879
Headache 13543
Dyspnoea 13100
Pyrexia 13031

29. Country
MAB
reports
Ukraine
1
Latvia
9
Estonia
21
Russian Federation
23
Lithuania
55
Serbia
73
Slovenia

30. SBPs provide
An opportunity to engage in PPP for PV in LMIC
MAH of generic and innovator biotherapeutics are
obliged to invest in PV
Generics are often used in LMIC
Through PV of SBPs, possible to create PV systems in
LMIC
That will be used also for other medicines (not only SBP)
Governments and Pvt industry should work out a
model
Data on products (MAH & Regulator)
PV System and PV capacity in country

31. www.who.int/medicines/areas/quality_safety/safety_efficacy/en

32. But we do need to build structures and best
practices because…
Dying from a disease is sometimes unavoidable. But
dying from an adverse drug event is unacceptable
Dr Vladimir Lepakhin, ex Assistant Director General, World
Health Organization