On this page: Medicines that must comply with the Order | Medicines that are not subject to the Order | Structure of TGO 101
Medicines that must comply with the Order
Discrete oral dosage forms
TGO 101 applies to three types of discrete oral dosage forms: tablets, capsules and pills. Assuring the quality of medicines manufactured in this way is important to ensure that they deliver their intended therapeutic effect and to provide a measure of continuing consistency in performance over time.
Various categories of tablets are recognised dosage forms in Australian approved terminology for therapeutic goods. These include coated and uncoated tablets, effervescent tablets and modified release tablets. Compressed lozenges, which are designed to dissolve or disintegrate in the mouth, are considered to be tablets.
Capsules can be hard or soft; the contents may be present as powders or liquids. Release of the active ingredients from capsules can also be modified in several ways, for example, enteric capsules.
Pills differ from tablets as they are manufactured using wet massing, piping and moulding. They can be coated, but usually contain only certain limited excipient ingredients and are typically manufactured and supplied as part of traditional medicine paradigms.
Release vs expiry specifications
Medicines must comply with TGO 101 throughout their shelf-lives. Sponsors may choose to apply release specifications that have tighter limits than the requirements of the Order. Such an approach can assist in compliance of a medicine at the end of its agreed shelf-life.
Medicines that are not subject to the Order
Other discrete dosage forms
Other discrete dosage forms for oral administration, such as soft lozenges and pastilles, are not required to comply with this Order. Medicines supplied in these dosage forms must comply with any relevant default standard, as recognised in the Therapeutic Goods Act 1989 (the Act). These default standards are relevant monographs in the European Pharmacopoeia (EP), the British Pharmacopoeia (BP) and the United States Pharmacopeia - National Formulary (USP).
Goods not required to be on the ARTG
TGO 101 applies to medicines that are registered or listed on the Australian Register of Therapeutic Goods (ARTG). Some medicines can be supplied in Australia without being on the ARTG. These include medicines that are compounded for supply to particular patients by registered health professionals. Tablets, capsules and pills manufactured in this way do not have to comply with the requirements of the Order. These medicines must comply with the default standards identified in the Act.
Other exempt medicines
Therapeutic goods, which are tablets, capsules or pills, entered on the ARTG as 'export only' medicines do not have to comply with TGO 101.
Some active ingredients used in tablets, capsules or pills cannot be measured in a way that is meaningful for the limits specified in TGO 101. These include radiopharmaceuticals where the effectiveness of the medicine is not measured by the amount of active ingredient present. These types of medicines are exempt from the Order.
Exempt medicines are described in section 7 of TGO 101.
Structure of TGO 101
Part 1 of the Order outlines its scope and application, including commencement dates and definitions of key terms.
Part 2 of the Order contains the requirements for tablets and capsules. Divisions within this Part describe the differences between applying an applicable monograph's requirements and the Australian specific requirements.
If an applicable monograph (there can be more than one) does exist, the sponsor can elect to comply with the applicable monograph in line with the requirements in Division 2 of Part 2. Alternatively, the sponsor can elect to comply with Division 3 – Australian specific requirements. In the absence of an applicable monograph, a medicine must comply with the requirements in Division 3.
Part 3 of the Order contains the requirements for pills, where 'pill' is defined in section 4 of Part 1.
Tablets, capsules and pills manufactured for supply in Australia may also be supplied in other countries. TGO 101 recognises:
- monographs in the BP, EP and USP as equivalent default standards and
- that not all medicines have applicable monographs in these pharmacopoeia.
The alternative sets of requirements included in the Order allow flexibility for sponsors to decide with which set of requirements their medicine must comply.
If a medicine that is a tablet or capsule is subject to an individual monograph in the EP, BP or USP, the medicine's sponsor can choose to comply with any one of those, in conjunction with any specific requirements prescribed in the Order. Alternatively, the sponsor could choose to comply with the Australian specific requirements set out in TGO 101. Meeting any one of these sets of requirements demonstrates compliance with TGO 101.
Variations to BP/EP/USP monographs
In some instances, TGO 101 will require additional tests to those set out in the relevant individual BP/EP/USP monograph.
In other instances, TGO 101 will allow fewer or different tests from that set out in the relevant individual BP/EP/USP monograph.
'Applicable monographs'
The BP, EP and USP each differentiate between general monographs (or chapters) and monographs for specific ingredients or finished goods. Each pharmacopoeia explains in the General Notices that individual or specific monographs must be read in conjunction with the general monographs or chapters. This relationship is recognised in the definition of 'standard' in section 3 of the Act. The definition also states that these monographs and chapters must be read and applied with consideration of the General Notices section of the relevant pharmacopoeia.
TGO 101 identifies relevant individual or specific monographs as 'applicable monographs'. In accordance with the Act, this means that the applicable monographs include any relevant requirements in the general monographs or chapters of that pharmacopoeia. The exact nature of that relationship should be confirmed by reading the relevant General Notices.
Monographs for dietary supplements in the USP are considered to be applicable monographs for the purposes of TGO 101.
Medicines that do not have an applicable monograph in the EP, BP or USP must meet, at a minimum, the Australian specific requirements in TGO 101.
Dissolution testing
Compliance with dissolution requirements is mandatory for:
- A registered tablet or capsule citing compliance with an applicable monograph, where that monograph includes a dissolution requirement
- A registered tablet or capsule citing compliance with an applicable monograph where:
- that monograph does NOT include a dissolution requirement, BUT
- another relevant default standard DOES include a dissolution test for an active ingredient present in the medicine.
In this case, a suitable dissolution test for the tablet or capsule is required.
- Any modified-release tablet or capsule,
Delayed release dosage forms, such as gastro-resistant soft gel capsules, may use disintegration testing or equivalent to demonstrate appropriate release of active ingredients.
- Tablets and capsules registered or listed on the ARTG claiming modified-release properties.
- Any tablet or hard capsule that contains 100 micrograms or more of folic acid
- Each active ingredient in a registered medicine:
- citing compliance with the Australian specific requirements and;
- where the active ingredient is subject to a test for dissolution as part of a specific or individual monograph in the BP, EP or USP for a tablet or capsule. The Order notes that a 'suitable' test is required in these circumstances. This allows, with appropriate justification, for some deviation from pharmacopoeial methodology if necessary.
Listed medicines are not required to demonstrate compliance with dissolution tests, with the exception of dosage units described as modified release or those containing folic acid.
The Order notes situations where a 'suitable' dissolution test may be appropriate. This allows, with appropriate justification, for some deviation from pharmacopoeial methodology and may, in some instances, require no dissolution test. Capsules containing liquids and modified release dosage forms such as gastro-resistant capsules would not typically require a test for dissolution.
Registered and listed medicines
Some requirements for medicines listed on the ARTG are different to those applied to registered medicines. These are set out in TGO 101.
The following table summarises the requirements and sections of the Order that apply to these different types of medicines.
| Registered tablet or capsule following a monograph | Registered tablet or capsule following Aust. requirements | Listed tablet or capsule following a monograph | Listed tablet or capsule following Aust. requirements | Pills | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Assay | As per applicable monograph | 8(1)(a) |
90-110% Vitamins, minerals, enzymes, probiotics comply with Schedule 2 |
8(1)(b) 14 |
As per applicable monograph | 8(1)(a) |
90-120% Vitamins, minerals, enzymes, probiotics comply with Schedule 2 |
8(1)(b) 15 |
90-120% Vitamins, minerals, enzymes, probiotics comply with Schedule 2 |
27 |
| Microbiological assay of antibiotics * | As per applicable monograph | 8(1)(a) | Yes, for antibiotics to estimate potency | 14(3) | No | No | No | |||
| Dissolution not required for chewable, effervescent or dispersible goods |
As per applicable monograph, OR if any other relevant monograph for tab/capsule with the active ingredient(s) requires it |
8(1)(a) 11 |
Yes, when any relevant monograph with the active ingredient(s) requires it, and for modified release goods. | 17 | As per applicable monograph |
8(1)(a) 17(2) |
Yes, for modified release goods. | 17(2) | No | |
| Folic acid dissolution | Complies with USP<2040>, unless the good is chewable, dispersible or effervescent, or contains less than 100 micrograms of folic acid (sections 10, 15) | |||||||||
| Disintegration | As per applicable monograph | 8(1)(a) | Yes, unless a dissolution test is performed | 18(2) | As per applicable monograph | 8(1)(a) | Yes, unless a dissolution test is performed | 18 | Yes | 26 |
| Dispersion | As per applicable monograph | 8(1)(a) | Yes, for dispersible goods only | 19 | As per applicable monograph | 8(1)(a) | Yes, for dispersible goods only | 19 | No | |
| Uniformity of dosage units | As per applicable monograph | 8(1)(a) | Yes | 20 | As per applicable monograph, or uniformity of mass/weight | 8(1)(a) | Yes, or uniformity of mass | 20 | Yes | 25 |
| Uniformity of weight/mass | As per applicable monograph | 8(1)(a) | No | Yes, instead of uniformity of dosage units | 12 | Yes, unless a uniformity of dosage unit test is performed | 20 | Yes | 25 | |
| Solvents | As per applicable monograph | 8(1)(a) | Yes | 16 | As per applicable monograph | 8(1)(a) | Yes | 16 | Yes (water) | 24 |
| Heavy metals | As per applicable monograph | 8(1)(a) | Yes | 16 | As per applicable monograph | 8(1)(a) | Yes | 16 | Yes | 28 |
* Microbiological assay only applies to antibiotics whose efficacy is assessed by a potency assay. It does not relate to microbiological contamination or the requirements of Microbiological Standards for Medicines. See BP Appendix XIV A or Ph. Eur. Method 2.7.2