An agency of the European Union

Post-approval benefit risk monitoring of vaccines: EMA perspective ESCAIDE, Stockholm, 30 November 2016

Presented by Dr. Marco Cavaleri Head of Office, Anti-infectives and Vaccines, EMA

EMA legislative mandate Explicit legal mandate to: • authorise vaccines • Risk management of vaccines (post-authorisation data collection and

risk minimisation) • Collection of safety data through e.g. Adverse Drug Reactions (60,000

per month) • Post-authorisation safety studies - impose on companies • Post-authorisation safety studies – protocols and results • Post-authorisation efficacy studies – impose on companies • Post-authorisation efficacy studies – protocols and results • Benefit risk monitoring of vaccines • Action if benefit risk changes: Variation; Suspension; Revocation

• Obligation to maintain database of all products on EU market (Art 57)

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•As part of the pharmacovigilance system, the marketing authorisation holder shall operate a risk management system for each medicinal product [DIR Article 104]

•Holders of MA granted before 2 July 2012 shall not be required to operate a risk management system for each medicinal product [REG Article 21]

•However: ‘The Agency may impose the obligation to operate risk management system...’ [REG Article 21 (2)]

RMP Requirements for MAH

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Information Flow in the RMP

I Product Overview

Safety Efficacy

IV Plans for Post-authorisation Efficacy studies

V Risk Minimisation Measures

III Pharmacovigilance Plan

II Safety Specification

VI Summary of RMP

Part II Safety Specification Information Flow

Identify: What is known! What is not known?

Drug Disease Target population

•Pharmacodynamics •Pharmacokinetics

•How will it be used? •Adverse event profile

•Class effects? •Interactions?

•Level of confidence?

•Who was studied? •Who wasn’t studied?

•Risk factors? •Which events can we

expect in this population?

•Natural history •Epidemiology

•What events occur as part of disease?

Important identified risks Important potential risks

Missing information

Safety Specification

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Safety concerns

Part III Safety concerns

Pharmacovigilance Plan

Safety concerns

Identify and characterise!

Routine activities •Collection of ADRs

•Case report follow-up (questionnaires)

•Signal Detection •PSURs

•Annual Reports •Literature review

Additional activities •Active surveillance

•Registry •Record linkage (eHR) •Case-control studies

•Cohort studies •Drug utilisation studies

•Clinical trials

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Additional activities

•Assessment of the effectiveness of

risk minimisation measures (e.g.

DUS)

Routine Risk Minimisation •Legal status

•Pack size •SmPC

•Package leaflet •Labelling

Additional Risk Minimisation •HCP educational program

•Patient educational program •Prescribing algorithm/checklist •Controlled access programme

•Other (e.g. DHPC, PPP)

Risk Minimisation Measures

Safety concerns

Prevent or Minimise!

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Part V Risk Minimisation Measures

Collaboration

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Collaboration – added value

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Collaboration - constraints

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PPPs - Collaboration with Contributing Funder(s)

10 Draft proposal

PPPs - Partnership with shared responsibility and funding

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2015-2016 LAIV/IIV VE estimates for H1N1 in 2-17 years

In US ACIP withdrew recommendation for LAIV for 2016-2017

Influenza Vaccine Effectiveness (IVE) studies(I)

• Rationale: continuous VE monitoring due to change in vaccine composition:

from a regulatory perspective, need to generate brand-specific data to contribute with important information to the overall clinical evidence available for each influenza vaccines, especially new vaccines

Studies to be conducted in line with Good Epidemiological Practice (GEP) guidelines and with ENCePP guidelines. Companies should liaise with organisations/institutions/public health authorities who have experience in IVE and who have implemented a functioning infrastructure to conduct multicentre studies

Studies currently included in RMP Pharmacovigilance plan to make them enforceable, but not related to safety concern

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• Data to be gathered yearly and brand-specific • difficulties to reach this objective are acknowledged and to be considered

at the time of assessment • time lag for setting up efficient system providing consistent results • Interpretation of the data not always straight forward • results of IVE studies may yield potential signals that require further

investigation to determine the drivers of estimated IVE • results from different seasons would have to be collected before any

conclusion could be drawn • regulatory actions may be considered if a specific concern (e.g. of a

manufacturing nature with a specific vaccine) is identified or strongly suspected by the deviation of the results from the expected pattern

Influenza Vaccine Effectiveness (VE) studies (II)

Look ahead

It is time to think about building a sustainable

infrastructure at EU level based on PPP for

monitoring Benefits and Risks of vaccines in

the post-authorisation phase in the interest of

public health

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Conclusion

• Need for EU level studies: safety, efficacy, effectiveness, benefit-risk. • Key role of public health authorities in the collection of these data • Need to establish governance • Need to clarify roles and responsibilities of different stakeholders • Funding models (complementarity between industry and public

funding) • ADVANCE has explored governance models which will be discussed in a

workshop at EMA in 2017 • EMA is committed to collaborative approach (technical and

governance)

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