The regulation of complementary medicines in Australia - an overview

April 2006

Introduction

In Australia, medicinal products containing herbs, vitamins, minerals, and nutritional supplements, homoeopathic medicines and certain aromatherapy products are referred to as 'complementary medicines'. These are regulated as medicines under the Therapeutics Goods Act 1989ⁱ (the Act). Complementary medicines comprise traditional medicines, including traditional Chinese medicines, Ayurvedic medicines and Australian indigenous medicines (see Figure 1).

Figure 1 - Classes of complementary medicines

COMPLEMENTARY MEDICINES
Herbal Medicines			Traditional Medicines				Vitamins & Minerals				Nutritional Supplements				Homoeopathic Medicines			Aromatherapy Products
	Ayurvedic Medicines				Traditional Chinese Medicines				Other Traditional Medicines

Other terms sometimes used to describe complementary medicines include 'alternative medicines', 'natural medicines' and 'holistic medicines'.

Complementary medicines are generally available for use in self-medication by consumers and can be obtained from retail outlets such as pharmacies, supermarkets and health food stores. While the majority of complementary medicines are indicated for the relief of symptoms of minor, self-limiting conditions, many are indicated for maintaining health and well being, or the promotion or enhancement of health.

The regulatory framework for medicines in Australia

The Therapeutic Goods Administration (TGA) is responsible for administering the provisions of the Act. The overall objective of the Act is to ensure the quality, safety, efficacy, and timely availability of therapeutic goods, including medicines and medical devices, that are supplied in or exported from Australia. The Act came into effect in February 1991. While the Act provides a substantially uniform national system of controls over therapeutic goods, other Commonwealth and separate State and Territory legislation may apply to certain therapeutic goods. The Act includes requirements for all therapeutic goods as well as specific requirements for different types of medicines, such as advertising, labelling, and product appearance.

For the purpose of regulating complementary medicines, the Act¹ and the Therapeutic Goods Regulations 1990^{2 ii} (the Regulations) respectively define what is a complementary medicine and designate the types of active ingredients that may be used in such medicines.

A complementary medicine is defined as a therapeutic good consisting wholly or principally of one or more designated active ingredients each of which has a clearly established identity and a traditional use. Traditional use means use of the designated active ingredient that is well documented, or otherwise established, according to the accumulated experience of many traditional healthcare practitioners over an extended period; and accords with well-established procedures of preparation, application and dosage.

Complementary medicines in Australia are not subject to the standards and guidelines of the Codex Alimentarius Commission.

The TGA maintains the Australian Register of Therapeutic Goods (ARTG) <http:://www.tga.gov.au/docs/html/artg.htm>, a database that includes details of all therapeutic goods that are imported into, supplied in, or exported from Australia. It is a legal requirement that, unless specifically exempt or excluded, all therapeutic goods are included on the ARTG prior to their supply. Therapeutic goods cannot be included on the ARTG unless an application is lodged by a sponsor for those goods.

In consultation with industry, the TGA has developed the Australian Regulatory Guidelines for Complementary Medicines (ARGCM)ⁱⁱⁱ to assist sponsors of complementary medicines to meet their legislative obligations.

¹Section 52F of the Act - Definitions
²Schedule 14 of the Regulations - Designated Active Ingredients

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Complementary medicines: quality, safety and efficacy

In supporting the Act, the TGA's regulatory processes include three key elements: the licensing and audit of manufacturers, pre-market assessment of products, and a range of post-market activities. These elements are summarised below.

Licensing and audit of manufacturers

The Act requires each Australian manufacturer of medicinal products for human use to hold a manufacturing licence. It is an offence, carrying heavy penalties, to manufacture therapeutic goods without such a licence, unless the goods are exempt from this requirement. Licence holders are required to comply with the manufacturing principles of the Act, including compliance with Good Manufacturing Practice (GMP).

The Australian Code of Good Manufacturing Practice

Australian manufacturers of medicinal products are required to comply with the Australian Code of Good Manufacturing Practice (GMP) for Medicinal Products^iv, which is based entirely on the international standard, Guide to Good Manufacturing Practices for Medicinal Products, published by the Pharmaceutical Inspection Cooperation Scheme (PIC/S). The Australian Code applies to all medicines manufactured in Australia, including complementary medicines.

Compliance with the Australian Code of GMP is ascertained by carrying out pre-licensing audits and, thereafter, regular on-site audits of manufacturers of medicinal products. The TGA has GMP inspection agreements with some other countries and organisations to obtain inspection reports, GMP certificates and other GMP-related information about overseas manufacturers exporting or wishing to export medicinal products to Australia.

Pre-market assessment

The TGA uses risk-based pre-market assessment procedures. In determining risk and the evaluation process to be applied to complementary medicines, a number of factors are taken into consideration. These include:

• the toxicity of the ingredients (itself a complex of factors);
• the dosage form of the medicine;
• whether the medicine is indicated for a serious form of a disease, condition or disorder, or for the treatment, cure, management or prevention of a disease, condition or disorder;
• whether the use of the medicine is likely to result in significant side effects, including interactions with other medicines; and
• whether there may be adverse effects from prolonged use or inappropriate self-medication.

Medicines that are assessed to be of higher risk are individually evaluated for quality, safety and efficacy. Higher risk products approved by the TGA are included on the ARTG as Registered medicines. Efficacy is usually assessed by examining data from controlled clinical trials. However, where adequate information is available on each active ingredient, and it is well described in standard textbooks/guidelines, this may be used to support efficacy.

Listed medicines are low risk medicines and are included on the ARTG via a low-cost and streamlined electronic application and validation process. Listed medicines may only contain ingredients that have been evaluated by the TGA to be low risk, must be manufactured by licensed manufacturers in accordance with the principles of GMP and may carry indications only for health maintenance and health enhancement or certain indications for non-serious, self-limiting conditions. Most, but not all, complementary medicines included on the ARTG are Listed medicines.

Listed and Registered medicines are differentiated on the product label by the designation, 'AUST L' or 'AUST R' respectively, followed by a unique number.

Ingredients permitted in Listed medicines

Listed medicines may be supplied only if they contain active ingredients permitted under Schedule 4 of the Regulations³. These are substances that have been evaluated by the TGA and found to be of low risk. To be consistent with their use in low-risk medicines, some ingredients are subject to conditions. These include requirements for advisory or warning statements on product labels, limits on plant part and/or preparations, quantitative limits, or substance-related restrictions. A consolidated list of substances that may be used as active ingredients in Listed medicines, including herbal substances, is available on the TGA web site.^4,v

³Commonwealth of Australia, Schedule 4, Therapeutic Goods Regulations 1990 as amended.
⁴ Substances that may be used in 'Listed' medicines in Australia <http:://www.tga.gov.au/cm/listsubs.htm>

Safety of ingredients for use in Listed complementary medicines

The safety of complementary medicine substances for use in Listed medicines is established through an evaluation process that aims to ensure that any substance approved for use in Listed products is low risk. However, where risks or potential risks are identified in association with the use or uses of a particular substance (for example, in its use by particular population subgroups, such as children or pregnant women, or in its interactions with other medicines), certain restrictions and/or controls may be imposed (such as the use of label advisory information etc) to manage the risk, but the substance may still be eligible, with restrictions, for use in Listed medicines.

Quality standards for ingredients for use in Listed complementary medicines

The Act defines the quality standards applicable to all therapeutic goods. For regulatory purposes, the British Pharmacopoeia (BP) is currently the source of official standards. The BP is supplemented by Therapeutic Goods Orders (TGOs) <http:://www.tga.gov.au/legis/tgo.htm>, which are developed by the TGA through a process of industry and other stakeholder consultation in response to a particular need, such as where there is no coverage by the BP or where Australian-specific requirements are appropriate. For example, TGO 56^vi describes the tests and acceptance criteria to be applied to tablets, capsules and pills. Quality standards for specific products may also be established through the Listing or Registration process.

Where a new complementary substance is covered by a monograph in the BP, this standard must be applied in its entirety, unless otherwise justified to the TGA. The requirements of applicable general monographs of the BP must also be met, except where a justification for not doing so is authorised by the TGA.

The TGA considers the suitability of other national or international pharmacopoeial monographs or standards for a substance on a case-by-case basis. In many instances, there are no applicable monographs, and a compositional guideline must be developed by the sponsor. A compositional guideline is a summary of descriptions, tests and limits that defines the composition and relevant characteristics of the substance. Where the pharmacopoeial monograph or standard sufficiently characterises the substance, a separate compositional guideline is not required.

It should be noted that a monograph or standard is designed to provide a means of controlling the quality of a substance. It is not intended to characterise the material to the extent required for entry in the ARTG. The compositional guideline should allow for characterisation as well as quality control of the substance. The ARGCM contains guidance on the criteria for compositional guidelines.

Efficacy of Listed complementary medicines

Consistent with low risk, Listed complementary medicines may only carry indications and claims for the symptomatic relief of conditions (other than serious disease, disorders, or conditions), health maintenance, health enhancement and risk reduction. The indications / claims on Listed medicines are not subject to pre-market evaluation at the time of Listing. However, the Act requires that, at the time of Listing, sponsors certify that they hold the evidence to support indications and claims made in relation to Listable goods. The evidence held by sponsors must be sufficient to substantiate that the indications and claims are true, valid and not misleading.

The TGA has developed the Guidelines for levels and kinds of evidence to support indications and claims^vii to assist sponsors in determining the level of evidence required to support indications and claims made for complementary medicines.

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Post-market regulatory activity

To maintain consumer confidence in the quality, safety and effectiveness of medicines supplied in Australia, an important feature of the TGA's risk management approach to both Listed and Registered complementary medicines is an appropriate level of post-market regulatory activity.

The essential elements of this systematic risk-based approach include:

• targeted and random desk-based audits of Listed products;
• monitoring of adverse reactions to complementary medicines;
• targeted and random laboratory testing of products and ingredients;
• targeted and random surveillance in the market place;
• an effective, responsive and timely recalls procedure;
• audit of GMP; and
• effective controls for the advertising of therapeutic goods.

Adverse drug reaction reporting

Post-market activities aim, among other things, to identify unsafe or potentially unsafe medicines and to take appropriate action to minimise the risk associated with their use. An essential element of this approach is to monitor adverse reactions to medicines, including complementary medicines.

An adverse reaction reporting system for medicines in Australia is well established. The Australian 'Blue Card' scheme covers all medicines and most health professionals. In addition, sponsors of all medicines included in the ARTG are under an obligation to report adverse reactions to the TGA.

All adverse reaction reports received by the TGA for complementary medicines are reviewed. The review may result in a various outcomes, including further analysis of database reports to investigate potential safety signals, publication of a report in the Australian Adverse Drug Reactions Bulletin <http:://www.tga.gov.au/adr/aadrb.htm> or medical journals to raise awareness of the reaction and/or removal of the product from the market.

Advertising

The advertising⁵ of therapeutic goods in Australia is subject to the advertising requirements of the Act (which adopts the Therapeutic Goods Advertising Code [TGAC] 2005 <http:://www.comlaw.gov.au>) and the supporting Regulations, the Trade Practices Act 1974 and other relevant laws.

The TGAC specifies the requirements for advertising of therapeutic goods to consumers. The objective of the TGAC is to ensure that the marketing and advertising of therapeutic goods to consumers is conducted in a socially responsible manner that promotes the quality use of therapeutic goods and does not mislead or deceive the consumer. Australia's framework for advertising controls also includes an industry-based self-regulatory component, comprising voluntary codes of practice with 'built-in' complaint-handling mechanisms. The peak industry associations in Australia, the Australian Self-Medication Industry and the Complementary Healthcare Council of Australia, administer these voluntary codes.

Advertisements to the general public for therapeutic goods appearing in mainstream media (eg newspapers, magazines, television and radio) must be pre-approved prior to their publication or broadcast.

⁵ 'Advertisement' in relation to therapeutic goods, includes any statement, pictorial representation or design, however made, that is intended, whether directly or indirectly, to promote the use or supply of the goods (Therapeutic Goods Act 1989).

Export of medicines

The export of medicines from Australia, including prescription, OTC and complementary medicines, is regulated by the TGA in order to protect health and safety by ensuring that medicines originating from Australia are of a similar quality and safety standard to those supplied domestically^viii.

The TGA:

• requires that medicines exported from Australia comply with necessary quality and safety standards;
• approves the supply of medicinal products for export;
• issues export certificates under a World Health Organization (WHO) Certification Scheme⁶;
• communicates with other regulatory authorities to maintain awareness of any potential quality and safety issues.

Medicines, including complementary medicines, approved for supply in Australia are automatically approved also for export by the sponsor or their agent, subject to other applicable export legislation. If a product has to include specific label warning statements in order to be eligible for Listing in the ARTG, and is also to be exported, these warning statements must remain on the label in order for the Australian Listing approval to extend to the exported product. Warning statements may be omitted only where the product is solely for export. Similarly, if labelling changes result in non-compliance with TGA labelling requirements, a 'solely for export' listing is required (see below).

⁶Australia is a participant in the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce. This scheme is intended to ensure the quality and safety of medicines which are ultimately sold in countries other than those where they were manufactured. The TGA, as part of its responsibilities under the WHO Certification Scheme, issues Certificates of Pharmaceutical Product (CPP) to exporters.

'Solely for Export' medicines

Medicines intended for export only, including products that would be regarded as complementary medicines in Australia, must be Listed on the ARTG before export. Generally, they must:

• be safe for their intended purpose of use;
• be manufactured under GMP;
• meet any standards applicable under Section 10 of the Act; and
• not be of an unacceptable presentation.

The export regulatory framework aims to provide a level of protection to the international community in terms of the safety and quality of products, while acknowledging that there are often valid reasons why products are not supplied on the Australian market. As part of the TGA's commitment to supporting a strengthened understanding in the importing country of the regulatory status of the product in Australia, the TGA may include a statement on the export certificate for 'export only' medicines, rather than simply certifying that the product is not licensed in the exporting country (as is required under the WHO Certification Scheme where this is the case).

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Summary

• Australia has a two-tiered regulatory system for medicines, based on risk
• Complementary medicines available for supply in Australia are included on the Australian Register of Therapeutic Goods (ARTG) as Listed (low risk) or Registered medicines (higher risk)
• Complementary medicines must be manufactured under the same code of Good Manufacturing Practice (GMP) as other medicines
• Listed complementary medicines may only contain ingredients permitted by the TGA for use in low risk medicines
• Listed medicines are restricted to indication and claims relating to health maintenance, health enhancement or non-serious, self-limiting conditions. Generally, they may not refer to a serious form of a disease disorder or condition or indicate they are for treatment or prevention.
• Registered complementary medicines are assessed individually for quality, safety and efficacy. Although Listed medicines are not assessed individually for efficacy, sponsors must certify to the TGA they hold evidence to support all indications and claims made for their products. This evidence may be audited by the TGA.
• Exported medicines are regulated to ensure that they are of a similar standard to those supplied in Australia.
• Post-market regulatory activities, including reporting of adverse reactions, audit of manufacturers and laboratory testing are an important element of ensuring the quality, safety and effectiveness of medicines regulated by the TGA.

References

1. Therapeutics Goods Act 1989 (the Act)
   <http:://www.comlaw.gov.au>
2. Therapeutic Goods Regulations 1990 (the Regulations)
   <http:://www.comlaw.gov.au>
3. Australian Regulatory Guidelines for Complementary Medicines (ARGCM)
   <http:://www.tga.gov.au/docs/html/argcm.htm>
4. Australian Code of Good Manufacturing Practice (GMP) for Medicinal Products
   <http:://www.tga.gov.au/docs/html/gmpcodau.htm>
5. Substances that may be used in 'Listed' medicines in Australia
   <http:://www.tga.gov.au/cm/listsubs.htm>
6. Therapeutic Goods Order No 56 (TGO 56) General standard for tablets, pills and capsules
   <http:://www.tga.gov.au/docs/html/tgo/tgo56.htm>
7. Guidelines for levels and kinds of evidence to support indications and claims
   <http:://www.tga.gov.au/docs/html/tgaccevi.htm>
8. Therapeutic Goods Administration - Policy for the Export of Medicines from Australia
   <http:://www.tga.gov.au/docs/html/export/exppol.htm>

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