WHO Medicines Safety Programme: Pharmacovigilance and risk minimization programs

for biological products

Dr Shanthi PalMedicines Safety Programme Manager

Essential Medicines and Health Products, WHOpals@who.int

pvsupport@who.int

Birth of modern pharmacovigilanceThalidomide – Phocomelia 1961

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.

WHO Programme for International Drug Monitoring

WHO-HQGeneva

WHO-HQGeneva

UMCWHO-CC Uppsala

UMCWHO-CC Uppsala

National Centres

UMC-A WHO-CC

Accra

UMC-A WHO-CC

AccraWHO-CC

RabatWHO-CC

Rabat

WHO-CCOsloATC DDD

WHO-CCOsloATC DDD

Pharmacovigilance in WHO

1. Exchange of Information2. Policies, guidelines, normative activities3. Country support4. Collaborations5. Resource mobilisation

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

What defines it

The WHO PV strategy

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

Challenges to Pharmacovigilance

Type of assistance needed

WHO International Drug Monitoring ProgrammeSituation 1990

WHO International Drug Monitoring ProgrammeSituation 2012

WHO strategy

Concept of genericsPatent expiry of medicines enables

GenericsCost savings because no need to invest in

further human trials for safety and efficacyCan use data from investigations with

innovator productsMore patients receive treatmentFurther investment in new medicines

Global Fund HIV/AIDS CoverageAfter 9 Rounds of proposals

0 5,0002,500

Kilometers ´

Traditional chemical medicinesrelatively smallStable moleculesNo need to repeat large-scale human trials

Safety monitoring is needed neverthelessUsed in 'other' environments & populations:

LMIC Comorbidities, nutritional effects, genetic

differencesLong-term effects

Pharmacovigilance in Global Fund grants

A 2010 analysis of Grant applications in the Global Fund A 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 Proposals31% had “acceptable reference to PV''Interviews: even if mentioned, PV not implemented in

practice

(Ref: Unpublished data, Pal, Xueref et al; 2010)

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

BiotherapeuticsGenerally large, complex moleculesproduced from living cells using

biotechnologycan pose rare but serious risks of unwanted

immune responsesRequire extensive testing and risk

management planning

Similar biotherapeutic products (SBPs)Copies or 'generic' versions of biotherapeutic

products (SBP)Are not exact copies of innovator products

Due to manufacturing processUnlike other generics, can't rely on data for /

from innovator productsNeed sufficient proof of similarity to

innovator product (both preclinical laboratory testing and clinical trials

Risk management plans are also essential

Guidance from WHODeveloped in 2009Published in 2010Based on EMA guidelines of 2006

Pharmacovigilance of SBPsManufacturer 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

Post approval activities for SBPsDue to potential of SBPs to provoke immune reactions

manufacturers to undertake post marketing surveillance to the same standards as RBP MAH

Pharmacovigilance plan should includeSafety monitoring as required of corresponding RBPSafety monitoring for additional risks identified

SBP manufacturers required to have PV systems in place at approvalQualified PV personnelmeans to report to NRAs where the reactions occur

in place

Traceability of Adverse eventsAEs may be product specificCritical information to assign AEs with

specific BPsADR report for any BP to include

INNProprietary or brand nameManufacturer's nameLot numberCountry of origin

Number of reports/million inhabitants/yearReporting last 5 years

Reports on Monoclonal antibodies (MABs) in WHO database (out of 8 million Individual Case Safety Reports, ICSRs)

TotalICSR 356787ICSRs with INN, trade names, indications

285327

Reports by country (top 10)

Top 5 ADRs with MAB in WHO databaseMedDRA_PT_name Number_of_ReportsFatigue 18208Drug ineffective 15879Headache 13543Dyspnoea 13100Pyrexia 13031

CountryMAB

reportsUkraine 1Latvia 9Estonia 21Russian Federation 23Lithuania 55Serbia 73Slovenia 187

SBPs provideAn opportunity to engage in PPP for PV in LMICMAH of generic and innovator biotherapeutics are

obliged to invest in PVGenerics are often used in LMICThrough PV of SBPs, possible to create PV systems

in LMICThat will be used also for other medicines (not only

SBP)Governments and Pvt industry should work out a

modelData on products (MAH & Regulator)PV System and PV capacity in country

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

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