Risk management plans for medicines and biologicals
When an RMP is required
You must submit an RMP with applications for registration or inclusion of all:
- new chemical entities
- class 3 and 4 biologicals in accordance with the TGA biological framework
We may request that you submit an RMP with applications for inclusion of selected class 2 biologicals when we identify a safety concern for which additional biovigilance or risk minimisation may be required.
Biological medicines (for example, vaccines, plasma derivatives and products of the fermentation of recombinant cell lines) are regulated as prescription medicines and are distinct from biologicals, which are living human or animal cells or tissues.
An RMP (or RMP update) will normally be expected with applications involving a significant change to an existing registration, such as a:
- significantly different population
- paediatric indication
- new dosage form or route of administration with inherently higher risk (e.g. oral tablets vs IV injection)
- new manufacturing process of a biotechnologically‐derived product
- other significant change in indication
What constitutes a significant change in indication
A significant change in indication occurs when the new (proposed) treatment target population differs materially from the previously approved target population for a medicine or biological. This may include (but is not limited to) a:
- new disease area
- new age group (e.g. paediatric indication)
- change from treatment of severe disease to treatment of a less severely affected population.
- change from 2nd line to 1st line treatment
- change to a combination treatment regimen (particularly for oncology indications, or where there is a significant safety concern with one or more of the included medicines)
When an RMP is required for biosimilars
An RMP is required for a biosimilar unless:
- there is an RMP for the reference product and there are neither additional pharmacovigilance activities nor additional risk minimisation activities being conducted, and
- the biosimilar will have identical indications and equivalent presentations to the reference product.
When an RMP is required for generics
An RMP is not required for generic medicines unless:
- there is an RMP for the reference product and a safety concern has been identified for which additional risk minimisation activities are being conducted
- there is no RMP for the reference product, but there are safety concerns with the reference product that have required specific risk minimisation activities. This includes, but is not limited to, thalidomide, leflunomide, clozapine, lenalidomide, isotretinoin and zoledronic acid and derivatives of these products
- we request one (requested by the Delegate)
Other times an RMP is required
In addition to the evaluation process, an RMP may be submitted or requested at any stage of a product's life‐cycle, during both the pre‐authorisation and post‐authorisation phases.
Ensure you submit an updated RMP if:
- there is a significant change to the benefit‐risk balance of one or more medicinal or biological products included in the RMP
- we request one when there is a concern about a risk affecting the benefit‐risk balance (see also Submitting RMP updates after regulatory approval)
Medicines and biologicals already on the ARTG
If a safety concern is identified, we may request an RMP (on a case‐by‐case basis) for medicines and biologicals that are already on the Australian Register of Therapeutic Goods (ARTG). We will notify you in writing, and provide our reason(s) for the request.
If you identify a safety concern requiring amendments to the approved product vigilance or risk minimisation activities, then you should submit an updated RMP (see Submitting Risk Management Plans after regulatory approval).
Any updated RMP submission requires a:
- summary table of changes between the updated RMP and the last RMP submitted to us
- cover letter stating the reason for submission
If an RMP is not required
This does not exempt you from routine product vigilance and risk minimisation requirements. Routine product vigilance (called pharmacovigilance for medicines and biovigilance for biologicals) requirements are set out in:
- Pharmacovigilance responsibilities of medicines sponsors: Australian recommendations and requirements
- Biovigilance responsibilities of biologicals sponsors: Australian recommendations and requirements (under development)
These requirements include, but are not limited to:
- collecting and collating in an accessible manner all suspected adverse reactions that are reported to the personnel of the company
- reporting serious adverse reactions to regulatory authorities
- continuous monitoring of the safety profiles of approved products, including signal detection and updating of labelling
- preparation of Periodic Safety Update Reports (PSURs), where applicable, for submission as specified in the approval letter, or when requested by the TGA
- meeting other TGA requirements
If you're not sure an RMP is required
If you are not sure whether you should submit an RMP with an application, contact us for advice as early as possible before you complete the Pre‐submission Planning Form (for medicines) or submit your application (for biologicals).
Email the RMP coordinator describing the proposed application. We will assess the requirement for an RMP, taking into account the information you provide, and notify you in writing. If no RMP is required, you can include our advice in Module 1.8.2 of your submission, as described in CTD Module 1: Administrative information and prescribing information for Australia.
Even if submission of an RMP is not required, we expect that you will continue to maintain any existing RMP relating to the product(s).