Section 12 of TGO 93 specifies tests and assay limits for medicinal cannabis products.
How to validate tests
For guidance on the principles and practice of validating tests:
- ICH Harmonised Tripartite Guideline Validation of Analytical Procedures: Text and Methodology Q2 (R1).
Cannabis plant tests
The cannabis plant you use must comply with the limits specified in Schedule 1, in addition to being positively identified as described in section 10 of TGO 93. The limits for the parameters apply on a dried basis, with the exception of the test for foreign matter. It may be appropriate to carry out additional tests to those specified in TGO 93 in certain circumstances.
Sample size and preparation guidance
Choose a sample size that is representative of the batch. For guidance on sample sizes and how to prepare herbal plant material for analysis, see:
- European Pharmacopoeia method of analysis Herbal Drugs: Sampling and Sample Preparation (2.8.20)
You must determine whether the cannabis plants used to manufacture the medicinal cannabis products meet the requirements of Schedule 1.
The following parameters are specified in Schedule 1:
- ochratoxin A
- foreign matter
- heavy metals (arsenic, cadmium, lead and mercury)
- total ash
The tests in Schedule 1 are standard pharmacopoeial tests applied to the cannabis plant used in the manufacture of medicinal products. For more information, see:
- European Pharmacopoeia general monograph Herbal Drugs (1433)
- Guidance on Specifications: Test Procedures and Acceptance Criteria for Herbal Substances, Herbal Preparations and Herbal Medicinal Products/Traditional Herbal Medicinal Products (CPMP/QWP/2820/00 Rev 2).
- Note that heavy metals must be reported in mg/kg, rather than ppm. Parts per million (ppm) is not sufficiently specific as it can be interpreted as mg/kg or mg/L.
Every batch must comply
Every batch of your medicinal cannabis product must be manufactured from cannabis plants that meet the requirements of Schedule 1. Generally, we expect all tests to be carried out on a routine basis to ensure that if a sample was tested by the TGA it would meet TGO 93 requirements.
However, in accordance with good manufacturing practice (GMP) considerations, you may perform reduced or rotational testing for non-critical tests provided that you are able to justify this reduced or rotational testing. For example, you may be able to justify reducing or not conducting pesticide testing if no pesticides are used in the cultivation of the cannabis plant.
You do not have to use the methods specified in Schedule 1 to test the cannabis plant. You could use:
- equivalent methods in established pharmacopoeia, including the United States Pharmacopeia-National Formulary
- suitably validated in-house or literature (non-pharmacopoeial) tests that are suitable for the intended purpose
However, in the event of a dispute, the methods of analysis specified in TGO 93 are the official methods.
In addition to testing the parameters specified in Schedule 1, consider performing additional tests on the cannabis plant from the general monograph on Herbal Drugs (1433), where such tests are warranted.
- Water or loss on drying:
- Consider performing tests for the cannabis plant in relation to water or loss on drying with appropriate limits to ensure that the cannabis plant does not contain excessive moisture that could facilitate the growth of microorganisms
- Consider performing tests for the cannabis plant in relation to radioactive contamination if the plant is grown in an area with potential for radioactive contamination, e.g. the Chernobyl region.
Assay of active ingredients in the product
You need to measure the concentration of the active ingredients in the finished product. The actual quantity of active ingredients must be within a specified range of the stated quantity [section 12(2) of TGO 93]. You may wish to apply tighter limits for release, to ensure the product still complies at the end of its shelf-life.
Active ingredient definition
An active ingredient is a therapeutically active component in the medicine's final formulation that is responsible for its physiological or pharmacological action (section 4 of TGO 93). In addition, the following ingredients are active ingredients in section 4(2) of TGO 93 for the purposes of TGO 93:
- any tetrahydrocannabinol (including any corresponding acid) greater than or equal to 1.0% w/w or w/v of the product
- any other cannabinoids (including any corresponding acid) greater than or equal to 2.0% w/w or w/v of the product
The term 'corresponding acid' is used because some cannabinoids such as THC and CBD ordinarily exist in the cannabis plant in the form of their corresponding acid, namely THC-acid and CBD-acid respectively. These acids form THC and CBD as a result of decarboxylation during storage or heating.
It is common practice to express the contents of cannabinoids in the cannabis plant as the total of cannabinoid and corresponding acid. For example, total THC is the sum of THC and THC-acid and total CBD is the sum of CBD and CBD-acid. The assay should be performed with reference to these total sums.
No particular test method is prescribed for calculating the average content of each active ingredient in accordance with section 12(2) of TGO 93. The assay method you use will depend on the active ingredient, the dosage form and the formulation of the product. You can use any suitably validated test method.
Examples of literature assay methods can be found in:
- Recommended methods for the identification and analysis of cannabis and cannabis products, United Nations Office on Drugs and Crime.
The assay limits are specified in relation to the stated content of each active ingredient. 'Stated content' is defined in section 4 of TGO 93. 'Stated content' means the quantity or proportion of each active ingredient:
- specified on the label
- disclosed in an application made under section 19 of the Therapeutic Goods Act 1989, whether or not the quantity or proportion is specified on the label
- disclosed in an application made under regulation 12A of the Regulations, whether or not the quantity or proportion is specified on the label
- purported to be present in a medicinal cannabis product that is dispensed, or extemporaneously compounded, for a particular person for therapeutic application to that person, in the manner mentioned in item 6 of Schedule 5 to the Therapeutic Goods Regulations 1990
- notified to be present for the purpose of clinical trials as described in item 3 of Schedule 5Ato the Therapeutic Goods Regulations 1990
Assay limits for various dosage forms
You need to test the concentration of the active ingredients in medicinal cannabis products. The assay limits for these tests are specified at section 12(2) of TGO 93 and will differ depending on the dosage form of products, specifically:
Herbal dosage form
When the product is in herbal final form (section 12(2)(a) of TGO 93), such as sachets of cannabis leaf material, each active ingredient, together with any corresponding acid, in a representative sample must be in the range of 80.0 - 120.0% of the stated content of that active ingredient.
Tablets or capsules
When the product is in tablet or capsule form (section 12(2)(b) of TGO 93), the average content of each active ingredient, together with any corresponding acid, as determined from a pooled sample of not fewer than 20 tablets or capsules, must be in the range of 90.0–110.0% of the stated content of that active ingredient.
Tablets or capsules on the ARTG
Medicinal cannabis products in tablet or capsule form that are registered on the ARTG must comply with the assay limits in TGO 101, which are tighter than those in TGO 93 (section 12 note).
Other dosage forms
For any other dosage form (for example, oromucosal spray) (section 12(2)(c) of TGO 93), the content of each active ingredient, together with any corresponding acid, in a representative sample must be in the range of 90.0 - 110.0% of the stated content of the active ingredient.