Australia explains rules for risk management plans
This article was originally published in SRA
Drug companies in Australia are being advised to discuss with the Therapeutic Goods Administration the need for a risk management plan when they are planning their registration dossiers for certain types of prescription medicines1. The move is part of a new TGA initiative that requires RMPs to be submitted for applications for new chemical entities and significant extensions of indications, for example.
The requirement for RMPs came into force on 1 April. It is one of the five initiatives that are part of the TGA’s Business Process Reform Project, which was unveiled earlier this year and which focuses on issues that were to be initially addressed through the proposed single regulatory authority for Australia and New Zealand (ANZTPA)2,3. Plans for the ANZTPA have been on hold since 20074.
As part of the reform project, the TGA introduced a new presubmission process (accelerated application entry) that requires drug sponsors to indicate whether they would be submitting an RMP.
Generally, an RMP will be required for drug registration applications for NCEs, significant extensions of indications, extensions to a paediatric population and applications to change the registration of a drug, where the change will result in different dosage forms, changes in the treatment population or changes in the safety profile of a medicine.
Additionally, if a safety issue arises, the TGA can request that an RMP be submitted for drugs that are already approved and on the Australian Register of Therapeutic Goods.
To help sponsors determine when an RMP should be considered, the TGA has formally adopted a related European Union guideline: Volume 9A – Guidelines on Pharmacovigilance for Medicinal Products for Human Use – of The Rules Governing Medicinal Products in the European Union5. Additionally, the TGA has issued a Q&A document to provide industry with basic information about the RMP initiative.
Simply put, an RMP represents a set of pharmacovigilance activities and interventions designed to identify, characterise and manage risks relating to a medicine. It should consist of an overview of the safety profile of a medicine, a pharmacovigilance plan and a risk minimisation plan. For example, it may include an observational cohort study to further identify the occurrence of adverse events that were equivocal or not seen during premarket trials. Examples of risk minimisation activities include providing educational material to prescribers.
While an RMP is not a substitute for routine pharmacovigilance activities, it is possible in some cases that the latter alone will be sufficient to address identified safety issues.
As the RMP covers the entire life-cycle of a product, it will have to be updated periodically to reflect new knowledge about a medicine’s safety profile.
Evaluating RMPs
An RMP, once submitted, will be evaluated by the TGA in parallel with other modules contained in the dossier. At this stage, all evaluations will be reviewed initially by the TGA’s Adverse Drug Reaction Advisory Committee and in 2010 by a new Medicines Safety Committee.
During the evaluation, consideration will be given to safety specifications provided by the sponsor at the time of application and additional safety concerns identified during the course of the TGA’s evaluation. The latter may result in amendments to the safety specifications submitted by the sponsor.
Once an RMP is evaluated and accepted, the TGA will be responsible for ensuring that postmarketing commitments contained in the plan are complied with. Some information about an RMP will also be provided in the Australian Public Assessment Reports.
References
1. TGA, Risk Management Plan, Q&A, 15 September 2009, www.tga.gov.au/pmeds/opm-bprproject-riskmanagement-qa.pdf
2. The Regulatory Affairs Journal – Pharma, 2009, 20(6), 376-377
3. The Regulatory Affairs Journal – Pharma, 2008, 19(10), 685-687
4. The Regulatory Affairs Journal – Pharma, 2007, 18(8), 567-568
5. TGA, Volume 9A – Guidelines on Pharmacovigilance for Medicinal Products for Human Use – of The Rules Governing Medicinal Products in the European Union, September 2008, www.tga.gov.au/docs/pdf/euguide/vol9/riskmmt.pdf