0. 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

1. 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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2. 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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3. 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
Activities commonly misclassified as risk min or PV – be clear about what is what.
 For each safety concern a risk minimisation activity is assigned in the RMP
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4. 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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6. Workflow of a RMP evaluation
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7. 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
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8. 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
Workshop presentations now available on TGA website
We found the workshop a valuable opportunity to meet people working on RMPs in industry so we could:
Better understand some of the challenges you face
Break down the barriers to communication
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9. 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
The RMP Questions and Answers provide guidance to industry about how the TGA treats RMPs
We provided you with the revised RMP Q&As to workshop attendees in March. To recap:
Before this, the last time the Q&As were updated was in 2012
In late 2014, the TGA sent out a proposed revised Q&A for members of Medicines Australia and GMIA to comment on.
We also provided a more detailed template for the ASA than we had previously provided, as this was something that sponsors had consistently asked us for. The revised ASA template was started by an ARCS working group – who we thanks for their work – and we built on what they had done
We had a good number of responses to the consultation, and these were constructive and comprehensive – thanks
The key themes of the responses were:
Reduce duplication in the ASA template: sponsors felt they were being asked to extract info from the EU RMP and reproduce it verbatim in the RMP – the value of this was questioned
Clarify processes, especially around:
When an RMP is required or not required and what to do if you’re unsure
When to submit an updated RMP to the TGA
We revised the Q&As and ASA in response to this feedback, and the final version of the doc was provided to attendees at the workshop in March.
The revised Q&As document will soon be up on the TGA website – we have been doing some further work on it to make it simpler and clearer. The document that goes up onto the TGA website will look a little different from the one you received at the workshop, but there are no changes to our requirements or the overall substance of the document.
If you would like a copy of the Q&A document in the meantime, please contact the RMP co-ordinator – but the document should be up on the website in the coming days.
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10. When is an RMP required? A New Chemical/Biological Entity
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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11. 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
Requirement to submit a RMP will be reviewed at the PPF stage by the RMP team
- Decrease in RMPs and consequently PSURs to be submitted
- Routine pharmacovigilance activities maintained
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12. 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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13. 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
If there is a new version of the EU RMP under consideration please let us know – if you can tell us when it is likely to be available this will help us to plan our effort. We don’t like surprises!
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14. 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
ASA is not a complete RMP but supplements the EU RMP (or core or global RMP)
ASA should always be provided with RMP, including unsolicited submission of RMPs and RMP updates
Updated template in Q&As was developed with stakeholder input, and in response to requests from industry – is more detailed than previous version and aims to minimise duplication for industry
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15. 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
At workshop, a few questions were about how to identify differences between EU and Australia where there were additional safety concerns applicable for Australia that didn’t appear in the EU RMP, or where an indication was being sought in the EU that had not yet been sought/approved in the EU – the ASA is the appropriate place to highlight these differences
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16. 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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17. 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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18. 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 –
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