Pharmacovigilance forum Risk Management Plans (RMP) - a TGA update - - PowerPoint PPT Presentation

Pharmacovigilance forum

Risk Management Plans (RMP) - a TGA update

Dr Jane Cook Branch Head Post-market Surveillance Branch Monitoring and Compliance Division, TGA ARCS Scientific Congress 2015 6 May 2015

Why have RMPs been required?

• Limited information from clinical trials (CTs)
• Not always representative of real world usage due to inclusion and exclusion

criteria in CTs

• Potential risks identified but not fully characterised during CTs
• Missing information in certain population groups – children, pregnant women and

the elderly

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What is a risk management plan for?

Outlines the risk management system for a medicine once it is available for use in Australia Comprises:

• Known safety profile
• Identified and potential safety concerns and where appropriate how they will be mitigated
• Missing safety information where this is known or can be predicted and how this will be managed

Focuses on:

• Monitoring – Pharmacovigilance Plan
• Minimising risks associated with the use of the product – Risk Minimisation Activities

Provides:

• Coverage of the life cycle of the product
• Assurance that all risks related to the use of a medicine have been considered and acted upon

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Risk minimisation activities

• Routine risk minimisation activities include:

– Product Information – Consumer Medicines Information – directions for use document – the labelling – the pack size and design – the legal (prescription) status of the product

• Additional risk minimisation activities include:

– education programs for patients – health care professional education programs – Dear Health Care Professional letters – controlled access programme

 For each safety concern a risk minimisation activity is assigned in the RMP

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Pharmacovigilance Plan

• Routine pharmacovigilance includes:

– collection, follow-up and reporting of adverse events – analysis of data and reporting in Periodic Safety Update Reports (PSURs)

• Additional pharmacovigilance includes:

– clinical trials – post-authorisation safety studies – drug utilisation studies – patient registries – physician surveys – prescription event monitoring

 For each safety concern a pharmacovigilance activity is assigned in the RMP

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Workflow of a RMP evaluation

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Guidance

• RMP Questions and Answers
• Australian-specific Annex Template
• Mandatory requirements for an effective application
• EMA Guideline on good pharmacovigilance practices: Module V – Risk

management systems

• RMP co-ordinator (rmp.coordinator@tga.gov.au)

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ARCS-TGA RMP workshop

• At the workshop in March, we discussed:

– The new Q&As – When an RMP is required – The purpose and format of the Australian-specific Annex (ASA) – When to submit post-market RMP updates – How to evaluate the effectiveness of risk minimisation activities

• There’s no ‘one-size-fits-all’ approach to RMPs

– Refer to guidance – Use judgement – Ask us if uncertain about requirements and process

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Revised RMP Q&As

• Proposed updated Q&As and ASA template sent to Medicines Australia and GMIA for members’

comment (Nov 2014)

• Main themes of feedback: reduce duplication, clarify process
• Final revised Q&As and ASA template provided to workshop attendees in March

– No substantive changes to requirements – ASA template better described – Clearer explanation of process and requirements – Ability to add further questions and answers as they arise

• Will soon be available on the TGA website

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When is an RMP required?

An RMP is always required for:

• A New Chemical/Biological Entity
• Higher risk (Class 3 and 4) biologicals
• Biosimilars
• Vaccines
• Generic medicines where innovator product has additional risk-minimisation

activities (check AusPAR, list in Q&As, ask if uncertain)

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When is an RMP required?

An RMP is usually required (but case-by-case consideration):

• Where the change to indication includes the following:

– significantly different population – paediatric patients – significant change in prescriber profile – Identification of a new safety concern

• New route of administration, dosage form or strength has inherently higher risk e.g. oral tablets vs

iv injection)

• Significant safety issue with one or both active ingredients in combination products

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Not sure if an RMP is required?

• Contact RMP coordinator well ahead of PPF lodgement – it’s never too early!
• Provide:

– trade name/generic name – indication (for generics: identical to innovator?) – strength, dose form and route of administration (for generics: identical to innovator?)

• We will respond in writing

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RMP format

• EU RMP + ASA
• If there is no current EU RMP, then a global or core RMP + ASA
• RMP version most recently accepted in EU, or one under consideration in the

EU? – Will depend on the specific circumstances – Let us know that there is a different version under consideration – Contact the RMP co-ordinator for advice if uncertain

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Australian-specific annex

Adapts the EU (or core/global) RMP to the Australian context Why is Australia different?

• Indigenous population
• Large Asian population
• Rurality/lack of access to specialist services
• State vs federal control over some aspects of how medicines are used
• Additional activities may require adaption to Australian systems
• Australian PI vs EU SmPC

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Australian-specific annex

• Required whenever an RMP is submitted (including updates) unless there is no

EU RMP and an Australian RMP is submitted

• ASA template sets out preferred format

− Other formats are acceptable if they contain the same information − Flexibility to change/add information to address different situations, e.g:

• additional safety concerns for Australia
• additional indications in Australia

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When to submit an updated RMP

Do submit an update

• On TGA’s request
• If significant changes to the RMP:

– new information that may change risk/benefit profile – changes to safety concerns – pharmacovigilance and/or risk minimisation activities added, terminated, or substantially altered

Don’t submit an update

• Routine document updates (EU guideline)
• Updates unrelated to product’s safety profile

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When to submit an updated RMP

We’ve completed a commitment in the ASA (e.g. a mail out of educational material to patients and prescribers). Should we update the ASA and resubmit to TGA?

• Conducting one step (e.g. a mail out) of a multi-step process as part of an ongoing risk-

minimisation commitment would not appear to create a material change to the RMP, therefore no requirement to submit an updated RMP to the TGA

• If evaluation of effectiveness of a risk minimisation activity has been completed, can submit the

results and conclusion of the evaluation

• TGA will need to accept any proposal to amend the RMP/ASA

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Top RMP tips

• Provide the EU RMP (if there is one) and an ASA
• Make sure all the information asked for in the ASA template is provided
• Provide all documents referred to in the RMP and ASA
• Address all RMP evaluator recommendations
• Whenever there’s an update, state clearly what has changed and why
• Ask us if you’re uncertain – rmp.coordinator@tga.gov.au

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