Therapeutic Goods (Listing) Notice 2015 (No. 5)

Administered by Department of Health, Disability and Ageing

Legislation au F2015L01469 Not in force Legislative Instrument

Select Document

EXPLANATORY STATEMENT

THERAPEUTIC GOODS (LISTING) NOTICE 2015 (NO. 5)

Subsection 9A(5), Therapeutic Goods Act 1989

OUTLINE

Therapeutic Goods (Listing) Notice 2015 (No. 5) (the Listing Notice) is a notice made by the delegate of the Minister for Health under subsection 9A(5) of the Therapeutic Goods Act 1989 (the Act).

The Listing Notice has the effect of enabling the ingredient named in the Listing Notices – ‘Levomefolate calcium’ – to be used as a therapeutically active ingredient in medicines that are listed on the Australian Register of Therapeutic Goods (the Register), subject to the relevant conditions specified in the Listing Notice.

The Listing Notice commenced on the day after it was registered on the Federal Register of Legislative Instruments (FRLI).

BACKGROUND

The Act provides for the establishment and maintenance of a national system of controls for the quality, safety, efficacy and timely availability of therapeutic goods that are used in Australia or exported from Australia. The Therapeutic Goods Administration (the TGA) is responsible for administering the Act.

Unless specifically exempted or authorised under the Act, therapeutic goods are required to be included on the Register before being supplied in, imported into, manufactured in or exported from Australia (sections 19B and 19D of the Act). Medicines are registered or listed on the Register, depending on the ingredients they contain and the therapeutic claims that are being made.

In general, products that contain low risk ingredients are referred to as listed medicines in Australia. Most listed medicines are considered to be of relatively low risk compared to other types of medicines, such as prescription medicines, as they may only contain ingredients that have been approved by the TGA as being of low risk and may only make limited therapeutic claims.

Subsection 9A(5) of the Act authorises the Minister for Health to publish a notice in the Commonwealth of Australia Gazette requiring that specified goods be included in the part of the Register for listed goods. Such notices generally require that goods containing particular ingredients be included in that part of the Register. Once the notice is in effect, persons may apply for the listing on the Register of new therapeutic goods that contain ingredients or substances of the kind set out in the notice.

A person can apply for a new ingredient or changes to certain conditions associated with an ingredient specified in a notice under subsection 9A(5). The TGA evaluates such applications, and the supporting data provided by the applicant, on the basis of safety and quality. The safety-focussed element determines whether the ingredient or substance is of sufficiently low risk to allow its inclusion in listed medicines, and the quality-focussed element characterises the precise and correct nature of the ingredient.

‘Levomefolate calcium’

Levomefolate calcium is the calcium salt of L-5-methyltetrahydrofolate (L-5-MTHF), the predominant form of folate in the body and the primary active metabolite of folic acid (the synthetic form of Vitamin B9). When ingested, Levomefolate calcium provides a form of folate that does not need to undergo enzymatic conversion before it can be utilised by the body.

Levomefolate calcium has been assessed by expert panels from Food Standards Australia New Zealand (FSANZ), the Joint Food and Agriculture Organisation /World Health Organisation Expert Committee on Food Additives (JECFA) and the European Food Standard Authority (EFSA), and is available within the European Union (EU) as a novel food ingredient and dietary supplement. Levomefolate calcium has Generally Recognised as Safe (GRAS) status in the United States, and is available for use in natural health products in Canada.

Several studies have demonstrated that Levomefolate calcium is essentially bioequivalent to folic acid, and is as effective as folic acid in providing folate supplementation. Single-dose, repeat-dose and reproductive toxicity tests in animal models have shown no treatment-related effects at the highest doses used. Additionally, there was no evidence of genotoxicity in a battery of ICH-compliant in vivo and in vitro tests. No adverse effects of Levomefolate calcium supplementation up to 17 mg per day were observed in numerous parallel, randomised, placebo-controlled human clinical trials. Levomefolate calcium is therefore considered to be low risk, and suitable for use in listed medicines as a source of folate, subject to appropriate restrictions on the maximum daily dose.

The upper daily level of intake of dietary folate equivalents established by National Health and Medical Research Council (NHMRC) is 1000 µg. This is based on studies showing that supplemental intake of folic acid in excess of 5 mg per day may mask, and precipitate or exacerbate, Vitamin B12 deficiency, potentially leading to adverse neurological effects. While it is possible that Levomefolate calcium may mask Vitamin B12 deficiency to a lesser degree than folic acid, there is no definitive evidence that this is the case.

Additionally, folic acid for oral use is included in Schedule 2 of the Poisons Standard, except in preparations containing 500 µg or less of folic acid/ folinic acid per recommended daily dose. Since Levomefolic acid is a derivative of folic acid and folinic acid (and therefore included in the Poisons Standard entry for both) and since it is essentially bio-equivalent to folic acid, the recommended dosages and restrictions applicable to folic acid and folinic acid are also appropriate for Levomefolic acid derived from Levomefolate calcium. Moreover, the restrictions are also applicable to preparations containing a combination of both Levomefolic acid derived from Levomefolate calcium and additional sources of Levomefolic acid (i.e.: folic acid, folinic acid and their derivatives).

Accordingly, the delegate of the Minister has determined that therapeutic goods containing ‘Levomefolate calcium’ as a therapeutically active ingredient can be included in the part of the Register for listed goods, when:

the preparation is for oral use only; and
either
- the preparation provides not more than 500 µg of Levomefolic acid from Levomefolate calcium per daily dose; or
- when used in combination with folic acid, folinic acid and/or their derivatives, the preparation provides not more than a total of 500 µg of folic acid, folinic acid and/or their derivatives in total per daily dose.

A monograph in the United States Pharmacopeia – National Formulary sets out the standards and requirements for ‘Levomefolate calcium’.

CONSULTATION

Consultation was not undertaken in relation to the making of the Listing Notice, as the notice is considered to be minor and machinery in nature, with low compliance costs for affected industry. The making of the Listing Notice does not involve any new regulatory steps for industry, but rather provides a basis for products containing this ingredient to access the listing process rather than registration, a significant benefit for sponsors.

The effect of this Listing Notice is that sponsors wishing to use ‘Levomefolate calcium’ as a therapeutically active ingredient in a medicine can list the medicine on the Register rather than having to apply to register it. Applications for new registered medicines are fully evaluated by the TGA for quality, safety and efficacy prior to inclusion in the Register, a process that is considerably more expensive and lengthy than the listing process.

The Office of Best Practice Regulation (OBPR) has advised that a regulatory impact statement is not required in relation to Listing Notices (OBPR Ref. 14416).

SUPPLEMENTARY MATERIAL – STATEMENT OF COMPATIBILITY FOR A LEGISLATIVE INSTRUMENT THAT DOES NOT RAISE ANY HUMAN RIGHTS ISSUES

Statement of Compatibility with Human Rights

Prepared in accordance with Part 3 of the Human Rights (Parliamentary Scrutiny) Act 2011

Therapeutic Goods (Listing) Notice 2015 (No. 5) – ‘Levomefolate calcium’

This legislative instrument is compatible with the human rights and freedoms recognised or declared in the international instruments listed in section 3 of the Human Rights (Parliamentary Scrutiny) Act 2011.

Overview of the Bill/Legislative Instrument

Therapeutic Goods (Listing) Notice 2015 (No. 5) (the Notice) is a notice made by the delegate of the Minister for Health under subsection 9A(5) of the Therapeutic Goods Act 1989 (the Act). The effect of the Listing Notice is to allow sponsors of orally ingested therapeutic goods containing ‘Levomefolate calcium’ as a therapeutically active ingredient to list, rather than register, those goods in the Australian Register of Therapeutic Goods (registration being a considerably more expensive and lengthy process than listing), subject to the conditions described in the Listing Notice.

Human rights implications

This legislative instrument does not engage any of the applicable rights or freedoms.

Conclusion

This legislative instrument is compatible with human rights as it does not raise any human rights issues.

Trisha Garrett

Delegate of the Minister for Health

Overview

The Therapeutic Goods (Listing) Notice 2015 (No. 5) was enacted under the Therapeutic Goods Act 1989 by the Minister for Health, through a delegate, to enable the use of 'Levomefolate calcium' as a therapeutically active ingredient in listed medicines, subject to certain conditions. This legislative instrument addresses the need to streamline the process for including new therapeutic ingredients in the Australian Register of Therapeutic Goods, reducing the regulatory burden on sponsors by allowing them to list rather than register products containing Levomefolate calcium, which is a low-risk ingredient. The notice facilitates quicker access to the market for these products, ensuring their safety and quality while maintaining the integrity of Australia's regulatory framework for therapeutic goods. The compatibility statement confirms that the notice does not raise any human rights issues, aligning with international human rights instruments.

Scope and Application

The Therapeutic Goods (Listing) Notice 2015 (No. 5) is a legislative instrument made under subsection 9A(5) of the Therapeutic Goods Act 1989, empowering the delegate of the Minister for Health to include 'Levomefolate calcium' in the Australian Register of Therapeutic Goods as a therapeutically active ingredient in listed medicines. The notice facilitates the listing process for medicines containing Levomefolate calcium, as opposed to the more rigorous registration process, provided that these medicines meet specific criteria. The notice applies to any therapeutic goods intended for oral use, containing Levomefolate calcium as an active ingredient, and must adhere to the maximum daily dose limits stipulated within the notice. This provision simplifies and expedites the pathway for these products to be included in the Register, benefitting sponsors by reducing costs and time compared to the registration process. The notice does not extend to therapeutic goods that do not meet the specified conditions for listing or those that fall outside the scope of the Therapeutic Goods Act 1989. The Listing Notice applies nationally across Australia, administered by the Therapeutic Goods Administration as part of the Commonwealth’s regulatory framework for therapeutic goods. The notice does not require consultation or involve new regulatory steps for industry but offers an alternative, streamlined process for listing certain therapeutic goods. It ensures that therapeutic goods containing Levomefolate calcium can be safely included in the Register under specified conditions, thereby facilitating their availability to the public. The notice is compatible with human rights, as it does not raise any human rights issues and aligns with the regulatory standards set by other jurisdictions.

Key Provisions

The Therapeutic Goods (Listing) Notice 2015 (No. 5) (the Listing Notice) allows the ingredient 'Levomefolate calcium' to be used in medicines listed on the Australian Register of Therapeutic Goods (the Register), provided certain conditions are met. Specifically, section 3 of the Notice specifies that Levomefolate calcium can be used in orally ingested medicines, with restrictions on the daily dose of the ingredient. The ingredient can be used alone or in combination with other sources of folate, but the total daily dose must not exceed 500 µg of folic acid, folinic acid, or their derivatives. The Listing Notice came into effect on the day after it was registered on the Federal Register of Legislative Instruments (section 4). The Listing Notice imposes obligations on parties who wish to include 'Levomefolate calcium' in their therapeutic goods. They must ensure that their products comply with the conditions set out in the Notice, such as the maximum daily dose of the ingredient. The Therapeutic Goods Administration (TGA) is responsible for evaluating applications for the listing of medicines containing 'Levomefolate calcium' and ensuring that the products meet the safety and quality standards set out in the Act. Sponsors of therapeutic goods must also comply with any other relevant requirements set out in the Act and associated regulations. Failure to comply with the Listing Notice or the Therapeutic Goods Act 1989 (the Act) may result in civil or criminal penalties. The Act provides for offences such as supplying therapeutic goods that do not comply with the Act or the Register, and for the imposition of fines and imprisonment. The maximum penalties for offences under the Act vary depending on the offence and the circumstances of the case. For example, the maximum penalty for supplying therapeutic goods that do not comply with the Act is a fine of up to $220,000 for an individual and $1,100,000 for a body corporate, or imprisonment for up to five years, or both. The maximum penalty for supplying therapeutic goods that do not comply with the Register is a fine of up to $110,000 for an individual and $550,000 for a body corporate. The TGA has the power to take enforcement action against parties who fail to comply with the Act or the Listing Notice, such as issuing infringement notices, seizing non-compliant products, and initiating legal proceedings. In summary, the Therapeutic Goods (Listing) Notice 2015 (No. 5) allows the use of 'Levomefolate calcium' in orally ingested medicines listed on the Register, subject to certain conditions. Parties who wish to include the ingredient in their products must comply with the conditions set out in the Notice and any other relevant requirements under the Act. Failure to comply with the Act or the Listing Notice may result in civil or criminal penalties.

Area of Law: Medical Law
Instrument: Notice
Concepts: Definitions & Interpretation; Regulatory Standards; Compliance Obligations

Interactions

Sourced from the Federal Register of Legislation at 26 August 2026. For the latest information on Australian Government law please go to https://www.legislation.gov.au.

Legislation content