RISK MANAGEMENT PLAN

By: Turacoz Healthcare Solutions

WHAT IS RMP?
Risk management plan (RMP) is a regulatory document
required for submission to health authorities

Includes information on:

a medicine's safety profile
how its risks will be prevented or minimised in patients

plans for studies and other activities to gain more

knowledge about the safety and efficacy of the
medicine
risk factors for developing adverse reactions
measuring the effectiveness of risk-minimisation measures

NEED FOR RMP?

At time of drug authorisation:
Information on safety of medicinal product is very limited
Not all actual or potential risks are known
Many of the risks are discovered after authorisation
RMP is needed for:
Characterisation of safety profile of the medicinal product
Planning of pharmacovigilance activities to characterise
risks and identify new risks

Planning and implementation of risk minimisation and

mitigation, and assessing the effectiveness of these activities

IMPORTANT DEFINITIONS
Identified risk
An untoward occurrence for which there is adequate evidence
of an association with the medicinal product of interest
Potential risk
An untoward occurrence for which there is some basis for
suspicion of an association with the medicinal product of
interest but where this association has not been confirmed
Missing information
Gaps in knowledge about a medicinal product, related to
safety or use in particular patient populations, which could be
clinically significant.

CURRENT GUIDELINES & OVERVIEW

In European Union (EU), RMPs are prepared as per Guideline on
good pharmacovigilance practices (GVP), Module V Risk
management systems
Overview of the parts of the RMP:
Part I

Product(s) overview

Part II

Safety specification

Part III

Pharmacovigilance plan

Part IV

Plans for post-authorisation efficacy studies

Part V

Risk minimisation measures (including evaluation of

the effectiveness of risk minimisation measures)

Part VI

Summary of the risk management plan

Part VII

Annexes

PART I PRODUCT OVERVIEW

Administrative information on RMP
Data lock point of RMP
Date of submission and version number
List of all parts and modules of RMP
Active substance information
Active substance and its pharmacotherapeutic group
Marketing authorization details
Description of the medicinal product like class, mechanism etc.
Indications
Dosage

Pharmaceutical forms and strengths

PART II SAFETY SPECIFICATION

Synopsis of the safety profile of medicinal product(s)
Summary of important identified risks of a medicinal product,
important potential risks, and missing information
Consists of eight RMP modules
SI-SV, SVII and SVIII correspond to safety specifications
SVI includes additional elements required to be submitted in the
European Union (EU)

PART II SAFETY SPECIFICATION (contd.)

Module SI

Epidemiology of the indication(s) and target

population(s)

Module SII

Non-clinical part of the safety specification

Module SIII

Clinical trial exposure

Module SIV

Populations not studied in clinical trials

Module SV

Post-authorisation experience

Module SVI

Additional EU requirements for the safety

specification

Module SVII

Identified and potential risks

Module SVIII

Summary of the safety concerns

PART III PHARMACOVIGILANCE PLAN

Structured plan for:
identification of new safety concerns
further characterisation of known safety concerns
investigation of whether a potential safety concern is real or not
how missing information will be sought
Includes following sections:

1. Routine pharmacovigilance activities

2. Additional pharmacovigilance activities (may include any nonclinical studies, clinical trials or non- interventional studies)
3. Action plans for safety concerns with additional
pharmacovigilance requirements
4. Summary table of additional pharmacovigilance activities

PART IV PLANS FOR POSTAUTHORISATION EFFICACY STUDIES

Required for products:

Where efficacy may vary over time

Where there are concerns about efficacy which can only be
resolved after the product has been marketed, or
When knowledge about the disease or the clinical methodology
used to investigate efficacy indicate that previous efficacy
evaluations may need significant revision
Includes following sections:
1. Summary of existing efficacy data
2. Tables of post-authorisation efficacy studies

PART V RISK MINIMISATION MEASURES

Details of the risk minimisation measures which will be taken to
reduce the risks associated with individual safety concerns

Includes following sections:

1. Routine risk minimization
Example: labelling, legal status, pack size etc.
2. Additional risk minimisation activities
Example: educational material
3. Evaluation of the effectiveness of risk minimisation activities
4. Summary of risk minimisation measures

PART VI SUMMARY OF ACTIVITIES IN THE RISK

MANAGEMENT PLAN BY MEDICINAL PRODUCT
Includes a summary of the RMP which shall be made publically available
[REG Art 23(3), Art 26(c), DIR Art 106(c) IR Art 31(2)]

Includes key elements of the RMP with a specific focus on risk minimisation
activities
Includes following sections:
1. Format and content of the summary of the RMP

2. Overview of disease epidemiology

3. Summary of treatment benefits
4. Unknowns relating to treatment benefits
5. Summary of safety concerns
6. Summary of risk minimisation activities by safety concern
7. Planned post-authorisation development plan
8. Summary of changes to the risk management plan over time

PART VII ANNEXES TO THE RISK

MANAGEMENT
1. Interface between RMP and Eudravigilance/EPITT (electronic only)
2. Current (or proposed if product is not authorised) local
(centralised/mutual recognition/decentralised/national) summary
of product characteristics (SmPC) and package leaflet
3. Worldwide marketing authorisation status by country (including EEA)
4. Synopsis of on-going and completed clinical trial programme
5. Synopsis of on-going and completed pharmacoepidemiological
study programme
6. Protocols for proposed and on-going studies in categories 1-3 of the
section Summary table of additional pharmacovigilance activities
in RMP part III

PART VII ANNEXES TO THE RISK

MANAGEMENT (contd.)
7. Specific adverse event follow-up forms
8. Protocols for proposed and on-going studies in RMP part IV
9. Synopsis of newly available study reports for RMP parts III-IV
10. Details of proposed additional risk minimisation activities (if
applicable)
11. Mock up examples in English (or the National language if the
product is only authorised in a single Member State) of the material
provided to healthcare professionals and patients as a requirement
of Annex II of the Commission Decision or as a requirement of
national authorisations including those using the mutual recognition
or decentralised procedure as applicable
12. Other supporting data (including referenced material)

SOURCE DOCUMENTS FOR RMP?

Summary of products characteristics (SmPC/SPC)
Patient information leaflet (PIL)

Clinical overview
Non-clinical overview
Literature evidence

WHEN IS RMP REQUIRED?

While applying for marketing authorization
At the time of significant change to the marketing
authorization.
Whenever there is a concern about a risk affecting the
benefit-risk balance of a medicine
Any changes in periodic safety update report (PSUR)
RMPs are continually modified and updated throughout
the lifetime of the medicine

THANKS

Life is more risk management, rather than exclusion of risks

-Walter Wriston