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Risk management plans for medicines and biologicals

Australian requirements and recommendations

29 March 2019

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When an RMP is required

An RMP is required with all submissions for:

  • registration of new chemical entities
  • provisional registration of a new medicine
  • a provisional extension of indication

Some application types (for example, extensions of indications and major variations) do not require an RMP in all cases. An RMP may be required for some application types as described in Table 2 - RMP requirements by application type, or with applications if a safety concern is identified for which additional pharmacovigilance or risk minimisation may be required.

We may also request an RMP or updated RMP at any stage of a product's life-cycle, during both the pre-approval and post-approval phases. You will be notified in writing and given our reason(s) for the request.

Refer to Application types that do not always require an RMP for further information about how to determine whether an RMP is required for your application types, and how to seek advice from the TGA.

Table 2: RMP requirements by application type
Application type RMP required?

Type A - New chemical entity/ biological* medicine (provisional, priority or standard pathway), excluding biosimilars

Always.

Type A, C and F for vaccines

For all new vaccines, extensions of indication and some major variations (see When is an RMP required for a variation?).

An updated RMP is required with or before strain change applications for seasonal influenza vaccines if changes to the pharmacovigilance plan are required, as described in the TGA annotations to EMA/PRAC/222346 Interim guidance on enhanced safety surveillance for seasonal influenza vaccines in the EU. The TGA will evaluate the updated RMP independently of the evaluation of the seasonal strain variation.

Biologicals*

For all new class 3 and 4 biologicals and for significant extensions of indication and other major variations as for prescription medicines (see When is an RMP required for a variation?).

On request for class 2 biologicals, when the TGA identifies a safety concern for which additional biovigilance or risk minimisation may be required.

Not required for class 1 biologicals.

Type B - New fixed combination of active ingredients

Only in certain circumstances (see When is an RMP required for a new combination of active ingredients?).

Type C - Extension of indication

When the proposed target population differs materially from the previously approved target population (see What is a significant change in indication?) or when the extension of indication has a current provisional determination.

A provisional extension of indication will always require an RMP.

Type D - Generic

Only in certain circumstances (see When is an RMP required for a generic?).

Type A - Biosimilar

Required, unless the originator has no additional pharmacovigilance or risk minimisation activities (see When is an RMP required for a biosimilar?).

Type F - Major variation

If the variation leads to new or heightened risks (see When is an RMP required for a variation?).

Category 3 application

An RMP is not required unless we request one. If the variation results in the need to amend additional risk minimisation materials, then these should be submitted for review (see When is an RMP required for a variation?).

Type J - Change to product information requiring evaluation of data

Only if requested by TGA.

Safety-related requests (SRR)

An updated RMP may be required as a result of a safety-related request (for example if there have been related changes to the summary of safety concerns, pharmacovigilance plan or risk minimisation plan). The RMP should be submitted as a post-approval update (see Submitting RMP updates after regulatory approval).

It may be provided with the SRR or after approval of the SRR and will be evaluated independently of the SRR.

*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 human cell and tissue products.

Application types that do not always require an RMP

For certain application types, we determine the need for an RMP to be submitted on a case-by-case basis. Our primary considerations for the following types of applications are:

  • whether the proposed change leads to new safety concerns, heightened risk for patients or new items of missing information
    • extensions of indication
    • new combinations of active ingredients
    • major variations
  • whether there are known safety concerns for the originator product for which additional activities are needed, or whether there are differences in their proposed usage that may lead to a new safety concern
    • generics
    • biosimilars

If you are unsure whether an RMP will be required, we recommend that you contact us for advice as early as possible before you lodge your pre-submission planning form (for medicines) or submit your application (for biologicals) (see If you're not sure an RMP is required).

What is a significant change in indication?

A significant change in indication occurs when the proposed target population differs materially from the previously approved target population for a product.

This may include (but is not limited to) a:

  • new disease area (e.g. seeking approval for a rheumatology indication for a product with an approved oncology indication). Extending the indication within the same disease area would not usually be considered a significant change. For example, two different solid tumour indications, or two related inflammatory conditions would not be considered significantly different if the line of treatment and patient populations are otherwise similar. However, if the extension was associated with another significant change, such as a new dose form or different dosing regimen, then an RMP may be required.
  • new age group (e.g. paediatric indication)
  • change from treatment of severe disease to treatment of a less severely affected population
  • change to a combination treatment regimen (particularly for oncology and antiviral indications, or where there is a significant safety concern with one or more of the included medicines)

When is an RMP required for a new fixed combination of active ingredients?

New fixed combinations of active ingredients will require an RMP when:

  • one of the active ingredients is a new chemical entity
  • one or more of the active ingredients requires additional risk minimisation
  • the indication of the combination differs from the indications of the individual active ingredients

An RMP may also be required if the combination leads to a new safety concern, or if there are new safety concerns for any of the individual active ingredients.

When is an RMP required for a generic?

An RMP is not required for generic medicines, unless:

  • there is an RMP for the originator product and a safety concern has been identified for which additional risk minimisation activities are being conducted, or
  • there is no RMP for the originator product, but there are safety concerns with the substance that have required specific risk minimisation activities. This includes, but is not limited to, thalidomide, leflunomide, clozapine, lenalidomide and isotretinoin and derivatives of these products, or
  • if the introduction of the generic may lead to a new safety concern, such as medication error (for example, different preparation instructions) or off-label use (for example, restricted indications), or
  • we request one

For information about what to include in RMPs for generics, see Requirements for RMPs for generics.

When is an RMP required for a biosimilar?

An RMP may be required if the biosimilar does not have all of the same indications and presentations as the originator product, so the need for risk minimisation for safety concerns resulting from medication error can be considered.

An RMP is not required for a biosimilar when:

  • there is an RMP for the originator product and there are neither additional pharmacovigilance activities nor additional risk minimisation activities being conducted,

and

  • the biosimilar will have the same indications (without omission of any indications), dosage forms, strengths and routes of administration as the originator product

If there is no RMP for the originator product then an RMP for a biosimilar version would generally not be required unless there is a significant difference in the use of the medicine.

If you are unsure about the RMP requirement for your biosimilar product then contact us prior to preparing your application.

When is an RMP required for a variation?

You should submit an RMP with an application for a major variation if the variation results in a new or heightened risk.

For example:

  • a new dosage form or route of administration with inherently higher risk (for example, injection vs tablets)
  • a new higher strength leading to a higher risk of medication error that could have a significant effect on patients
  • a larger pack size if this may increase risk

For minor variations, an RMP is not required unless we request one, but you should consider whether the changes result in a need to amend risk minimisation materials.

For example:

  • category 3 applications for changes to container type or pack size may lead to a need to change patient guides or instructions for use. You should include in your submission any risk minimisation materials with proposed amendments resulting from the variation. You do not need to submit an updated version of the RMP for evaluation for a category 3 application unless we ask for one.

If an RMP is not required

You must still comply with routine product vigilance and risk minimisation requirements if an RMP is not required. Routine product vigilance (called pharmacovigilance for medicines and biovigilance for biologicals) requirements are set out in:

Requirements include, but are not limited to:

  • telling us who your Australian pharmacovigilance or biovigilance contact person is through the TGA Business Services electronic portal
  • submitting any serious adverse reaction reports to us
  • notifying us of any significant safety issues you identify
  • keeping records pertaining to the reporting requirements and safety for your medicine (under Subsection 28(5)(ca) of the Therapeutic Goods Act 1989 (the Act))
  • answering any request from us for additional information fully and within the specified timeframe (under Subsection 31(1) of the Act)

If you are not sure an RMP is required

If you are not sure whether you should submit an RMP with an application, email the RMP coordinator describing the proposed application before you complete the Pre‐submission Planning Form (for medicines) or submit your application (for biologicals).

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) (see Submitting RMP updates after regulatory approval).

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