Listed medicines at risk of containing safrole

We have initiated targeted compliance reviews of a selection of listed medicines that are at risk of containing safrole.

If you are a consumer, please note that this is part of our normal review process and there is no immediate concern associated with the use of listed medicines.

Background

Safrole is a naturally occurring constituent at low concentrations in certain spices including sassafras, cinnamon, nutmeg, mace, star anise and black pepper. Prior to 1960, safrole was used extensively as a flavouring additive. However, animal and in-vitro studies have shown its genotoxic and carcinogenic effects, on the basis of which the use of safrole as a food and flavouring additive became strictly regulated.

In Australia, regulatory controls over therapeutic goods containing safrole are imposed by the Poisons Standard. Restrictions on the concentration of this substance are in place to minimise the risks of poisoning, misuse or abuse. Listed medicines must contain no more than 0.1% of safrole when it is for internal use, and no more than 1% when it is for topical application.

There are 12 ingredients approved for use in listed medicines, which may contain safrole as a constituent. Listed medicines including one or more of these ingredients could therefore be at risk of containing safrole in concentrations above the permitted limits. However, suitable risk management practices during manufacturing in combination with TGA’s post-market monitoring and testing activities are measures currently considered sufficient to mitigate such risk.

In line with the above, sponsors are expected to maintain appropriate records for demonstrating their medicine’s compliance with regulatory requirements relevant to safrole and therefore its safety.

Listed medicines may be subject to a compliance review at any time while they remain on the Australian Register of Therapeutic Goods (ARTG). This allows us to determine the compliance of these medicines with relevant regulatory requirements. As such, we intend to determine the compliance of medicines at risk of containing safrole with relevant requirements by undertaking targeted compliance reviews.

What sponsors of existing listed medicines need to do

Sponsors of listed medicines at risk of containing safrole are required to certify that the concentration of this substance in the medicine is within the limits imposed by the Poisons Standard. Therefore, if you are a sponsor of a listed medicine at risk of containing safrole, you are encouraged to:

• Verify that you hold chemical testing results, suitable risk assessments, evidence of adequate risk management measures and/or other appropriate records to demonstrate that your certification in relation to safrole is correct; and
• Ensure that such records are readily available in the event that your medicine is selected for a compliance review.

What the TGA will do

In the fourth quarter of 2020, we initiated desktop compliance reviews for a selection of listed medicines that contain one or more ingredients at risk of containing safrole. Some medicines were selected randomly and others were selected on the basis of regulatory intelligence.

Sponsors of such medicines have received a Request for Information notice informing them that their medicine is being reviewed and explaining the review process. Evidence received from sponsors in relation to the content of safrole in the finished goods and, if appropriate, other listing requirements, is being assessed.

If no compliance deficiencies are identified for a selected medicine, the review will be concluded and there will be no further regulatory action. If deficiencies are identified, samples of the medicine may be requested for laboratory testing at the TGA and the medicine may be cancelled from the ARTG, unless the sponsor takes corrective action to rectify the deficiencies.

A summary of the outcomes from this compliance activity will be published after the conclusion of the review.