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 Pharmacovigilance forum 1

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 Pharmacovigilance forum 2

Risk minimisation activities • Routine risk minimisation activities include: • Additional risk minimisation activities include: – Product Information – education programs for patients – Consumer Medicines Information – health care professional education programs – directions for use document – Dear Health Care Professional letters – the labelling – controlled access programme – the pack size and design – the legal (prescription) status of the product  For each safety concern a risk minimisation activity is assigned in the RMP Pharmacovigilance forum 3

Pharmacovigilance Plan • Routine pharmacovigilance includes: • Additional pharmacovigilance includes: – collection, follow-up and reporting of – clinical trials adverse events – post-authorisation safety studies – analysis of data and reporting in – drug utilisation studies Periodic Safety Update Reports – patient registries (PSURs) – physician surveys – prescription event monitoring  For each safety concern a pharmacovigilance activity is assigned in the RMP Pharmacovigilance forum 4

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Workflow of a RMP evaluation Pharmacovigilance forum 6

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) Pharmacovigilance forum 7

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 Pharmacovigilance forum 8

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 Pharmacovigilance forum 9

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) Pharmacovigilance forum 10

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 Pharmacovigilance forum 11

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 Pharmacovigilance forum 12

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 Pharmacovigilance forum 13

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 Pharmacovigilance forum 14

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 Pharmacovigilance forum 15

When to submit an updated RMP Do submit an update Don’t submit an update • On TGA’s request • Routine document updates (EU guideline) • If significant changes to the RMP: • Updates unrelated to product’s safety profile – new information that may change risk/benefit profile – changes to safety concerns – pharmacovigilance and/or risk minimisation activities added, terminated, or substantially altered Pharmacovigilance forum 16

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 Pharmacovigilance forum 17

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 Pharmacovigilance forum 18