7th International Executive Director Rotavirus Symposium Medical - - PowerPoint PPT Presentation

Pentavalent Rotavirus Vaccine European Risk Management Plan Pentavalent Rotavirus Vaccine European Risk Management Plan

Luc HESSEL Executive Director Medical and Public Affairs Sanofi Pasteur MSD

7th International Rotavirus Symposium

Lisbon, June 12-13, 2006

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The concept of Risk Management

• A strategic approach to ensure optimal use of a medicinal

product by individual patients and populations

• A global approach

Identification and detection of risks linked to the use of the vaccine Assessment , validation, quantification Management through appropriate strategies to minimise risk

• A paradigm change

From benefit-risk assessment to prevention of risk From passive surveillance to active anticipation From product safety to patient safety

From From Post Post-

• Marketing surveillance to

Marketing surveillance to Risk Risk Management Management

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European Risk Management System European Risk Management System

• 2001: introduction of the concept of risk management plans in the EU

legislation (Dir. 2001/83 EC)

• June 2005: enforcement of the regulation on pharmacovigilance plans

(CPMP/ICH/5716/03)

• December 2005: Guideline on risk management systems for medicinal

products for human use

Definition of ERMS

A set of pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risk relating to medicinal products, and the assessment of the effectiveness of those interventions

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Risk Management Strategy: objectives and actions Risk Management Strategy: objectives and actions

Detection Quantification Validation Minimisation Communication Identify Monitor Assess Update Prioritise Resolve / control Assess

RMS

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Key elements of Risk Management Plans (RMP) Key elements of Risk Management Plans (RMP)

• 1. Pharmacovigilance plan: a plan proposing

collection of data relevant to the safety profile of a medical product once it is marketed and aiming to demonstrate safety as well as identifying harm

• 2. Risk minimization strategies to reduce risk to

individual patients and populations

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Characteristics of rotavirus vaccines Characteristics of rotavirus vaccines Characteristics of rotavirus vaccines

• Live attenuated vaccines

Infectivity (immunosuppression), reassortment, reversion …

• Oral administration

Intestinal replication and shedding

• Target population: young infants from 6 weeks of age

Safety first

• Co-administered with other childhood vaccines

Interferences

• Prevention of infections due to several serotypes

Coverage and cross-protection Strain replacement

… and the Rotashield experience !

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Pentavalent RV vaccine RMP: Specifications Pentavalent RV vaccine RMP: Specifications

• Identified risks

No safety signal identified in clinical trials (> 36,000 vaccinees and > 100,000 doses)

• Potential risks

Extra-intestinal events reported to occur with wild-type RV Events not previously anticipated Intussusception (due to the history of Rotashield) Potential for strain replacement and emergence of new reassortants Transmission of vaccine virus from vaccinees to close contacts

• Important missing information

Use in immunocompromised infants (study planned) Safety and efficacy of PRV in developing world (studies planned)

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Pentavalent RV vaccine RMP : action plan Pentavalent RV vaccine RMP : action plan

• 1. Global routine pharmacovigilance, spontaneous reporting +

PSURs

unanticipated safety signals all other adverse events

• 2. Post-marketing safety surveillance trial (observational study in

44,000 children - USA)

Intussusception (rule out a RR of 2.5 with a 80% power) General short term tolerance (not pre-specified) Potential extra-intestinal manifestations

• Central nervous system : meningitis, encephalitis, paralysis, seizure
• Hepatotoxic events

Significant gastro-intestinal events Gastro-oesophageal reflux disease …

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3.Incidence of intussusception (IT): Prospective evaluation of the annual incidence of IT in children <2 years:

ESPED system: « German surveillance system for rare paediatric diseases » Birth cohort of 700,000 children will be monitored Start January 2006 Duration: min 2 years (6 monthly reports)

4.Transmissibility of the vaccine virus strain from vaccinees to close contacts, including immunocompromised

Study in infants born to HIV-infected mothers Inclusion of HIV-infected and HIV-exposed infants

Pentavalent RV vaccine RMP : Action plan Pentavalent RV vaccine RMP : Action plan Pentavalent RV vaccine RMP : Action plan

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Pentavalent RV vaccine RMP: action plan Pentavalent RV vaccine RMP: action plan 5.Rotavirus strain surveillance:evaluation of the potential for strain replacement or emergence of novel reassortants

G and P genotyping of RV positive stools samples Through European Foodborne Virus Network (11 EU countries)

6.Post-license effectiveness study

Will begin as soon as the vaccine is used with sufficient uptake to have enough power to assess its effectiveness

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Pentavalent RV vaccine: Risk Minimisation Plan

• Ready-to use liquid packaged in

single dose user-friendly tubes: no admixture or misuse expected

• Currently identified risks

associated with PRV few and minor

• Risk minimisation plan not

required

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• Rotavirus vaccines are the first vaccines with such a

large pre-licensure experience (since polio)

• They will be the first vaccines to follow the new EU

regulations on risk management

• This should contribute to support the implementation of

RV vaccination programmes and their acceptability by health care professionals and parents CONCLUSION