14.45 S Blackburn · • Systems for collecting adrs – SOPs – Co-licensing agreements • Systems for reporting adrs – Expedited reports – PSURs A Pharmacovigilance System

1

Risk Management PlansRisk Management Plans

Dr Stella BlackburnDr Stella Blackburn Phase I – III development

What am I supposed to do?

The Past ? The Reality

Risk Management!Risk Management!

The Legislation

Article 8 (3)(ia) of Directive 2001/83/EC requires the MAA to submit:

“a detailed description of the pharmacovigilance and, where appropriate, of the risk management system which the applicant will introduce.”

2

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This is company specific NOT product specific.This is company specific NOT product specific.Description of how the company will implement the PhV requirements in Regulation (EC) No 726/2004, and Directive 2001/83/EC as amended

Details found in the Chapter “Requirements for Pharmacovigilance Systems, Monitoring of Compliance and Pharmacovigilance Inspections” in Volume 9A of The Rules Governing Medicinal Products in the European Union

• PhV QP

• PhV Databases

• Systems for collecting adrs– SOPs

– Co-licensing agreements

• Systems for reporting adrs

– Expedited reports

– PSURs

A Pharmacovigilance System is different from a Risk Management System!

The Pharmacovigilance System

The Risk management System

Requirement for a RM System can be fulfilledby the submission of an EU RMP

Definition:a set of pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risksrelating to medicinal products, includingthe assessment of the effectiveness of those interventions

The EU Risk Management PlanThe EU Risk Management Plan

Part I• Safety Specification• Pharmacovigilance Plan

} ICH E2E

Part II• Evaluation of the need for risk minimisation activities,

if a need for additional risk minimisation activities

• Risk minimisation plan

Safety SpecificationSafety Specification(According to ICH Topic E2E)(According to ICH Topic E2E)

Non-clinical

• Toxicity

• General pharmacology

• Drug interactions

Safety SpecificationSafety SpecificationClinical• Limitation of human safety database

– Clinical trial population– Post-marketing exposure (if any)

• Populations not studied• Post-marketing experience (actual use vs SPC)• Adverse reactions

– Risks (identified or potential)• Identified and potential interactions• Epidemiology• Pharmacological class effects

3

Safety SpecificationSafety Specification

• EU Specific

� Potential for misuse for illegal purposes

� Potential for off-label paediatric use

� Potential for off-label use

� Potential for transmission of infectious agents

� Potential for overdose

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WhatWhat’’s the minimum s the minimum I can get away with?I can get away with?

Writing the Pharmacovigilance PlanWriting the Pharmacovigilance Plan

4

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Pharmacovigilance PlanPharmacovigilance Plan(According to ICH Topic E2E)(According to ICH Topic E2E)

• Actions proposed

�� AdditionalAdditional pharmacovigilance pharmacovigilance activitiesactivities (e.g. (e.g. active surveillance, intensive monitoring, active surveillance, intensive monitoring, PhEpiPhEpi studiesstudies))

� Routine pharmacovigilance (e.g. signal detection, adverse reaction reporting, PSURs )

Evaluation of the need for risk minimisation activities

Look at each important safety issue•• Discuss whether risk minimisation actions Discuss whether risk minimisation actions

neededneeded

•• Is the product literature sufficient for this Is the product literature sufficient for this purpose?purpose?

•• If not then risk minimisation plan neededIf not then risk minimisation plan needed

•• PotentialPotential for for medicationmedication errorerror

Doctor admits drug blunder killing

Wayne Jowett died a month after the mistake

A doctor has admitted the manslaughter of a teenage cancer patient who died after a hospital drug blunder.

Wayne Jowett, 18, died after a toxic cancer drug was wrongly injected into his spine rather than a vein.

Risk minimisation Plan

• Only needed if additional risk minimisation activities needed

• Should list safety concerns for which risk minimisation activities needed

• Should include both routine and additional risk minimisation activities

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Summary of activities in EU-RMP

Safety concern PhV Plan Risk Min Activities

1.

2.

3.

etc

Hepatitis• Study to

investigate the incidence and risk factors for hepatitis in Wonderdrug and other immuno-suppressant drugs using GPRD database

• Routine PhV. • Contraindication for patients with active viral hepatitis in section 4.3 of the SPC• Warning in section 4.4 of the SPC that LFTsshould be monitored monthly• Listed as ADR in section 4.8

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Situations when EU-RMP submitted II

• Situations where EU-RMP might be required when new authorisation via centralised procedure

�� ““fixed combinationfixed combination”” applicationsapplications

�� bibliographical applicationsbibliographical applications

�� hybrid medicinal product where the changes hybrid medicinal product where the changes compared with ref product suggest different riskscompared with ref product suggest different risks

�� ““known active substancesknown active substances””

• Significant changes to MA

� New pharmaceutical form

� New route of administration

� Significant change in an

� indication/patient population

Situations when EU-RMP submitted III

Unless agreed not needed}

• On request from the Competent Authority

• On company initiative e.g. safety issue with a marketed medicine

• Update to previous EU-RMP

Update to the EU-RMP

��

• updated throughout the lifecycle of the product

• safety specification will change over time

� results from other clinical trials� results from studies in PhV Plan� spontaneous reports and literature

• PhV Plan and Risk Min Plan will also change over time

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Documents

14.45 S Blackburn · • Systems for collecting adrs – SOPs – Co-licensing agreements • Systems for reporting adrs – Expedited reports – PSURs A Pharmacovigilance System