Regulatory Landscape for Minor Cannabinoids (Australia)

Regulatory Landscape for Minor Cannabinoids
Australia

The below version control table serves to document all updates made to the report. The purpose is to ensure the information is always accurate and up-to-date.

1. Current Regulatory Landscape

1.1 CBD - Prescription only (Rx)

1.1.1 Is CBD considered a narcotic in Australia?

No. CBD products are classified according to the Poisons Standard as Schedule 4 (Prescription Only Medicine). 

1.1.2 Are there registered drugs on the market? If yes, what are they, and which ingredient incl. the source (synthetic, Phyto, etc.)

The following products have been granted a marketing authorization by the TGA in Australia: 

1. Nabiximols (Sativex) - Oromucosal spray containing 80 mg/mL extracts from Cannabis sativa L., folium cum flore (Cannabis leaf and flower), corresponding to delta-9-THC (27 mg/mL) and CBD (25 mg/mL) with other cannabinoid components (56 mg/mL total cannabinoids). Indicated as a treatment for symptom improvement in patients with moderate to severe spasticity due to multiple sclerosis (MS).
2. Cannabidiol (Epidyolex) - Plant-derived oil-based formulation of CBD (100 mg). Adjunctive therapy of seizures associated with Lennox-Gastaut Syndrome or Dravet Syndrome.

1.1.3 What are specific regulations to consider?

Sponsors wishing to market a medicinal product in Australia must have their product included in the Australian Register of Therapeutic Goods (ARTG). 

Registration of all CBD products would be as a new chemical entity, via the Category 1 application pathway, with the requirement for submission of a full dossier in the CTD format.

1.1.4 What are the quality & safety points to consider?

A full CTD Module 3 is required to support registration. 

https://www.tga.gov.au/how-we-regulate/supply-therapeutic-good-0/supply-prescription-medicine/application-process/prescription-medicines-registration-process

Additionally, all products must comply with the Therapeutic Goods (Standard for Medicinal Cannabis) TGO 93.

https://www.legislation.gov.au/Details/F2022C01204

This includes both ingredients and finished products. TGO 93 specifies the minimum quality requirements for medicinal cannabis products. The current TGO 93 does not permit the use of synthetic cannabinoids.

1.1.5 Are there regulatory differences between the various sources of CBD (phyto, synthetic, biosynthetic)?

In accordance with section 8 of TGO 93, each active ingredient and any other cannabinoid that is not an active ingredient must be from the cannabis plant, and their chemical structure must not be modified or transformed in any way (including by chemical and other means). Therefore, at this time, synthetic and biosynthetic products are prohibited in Australia.

1.1.6 Is there any special scheme for CBD or cannabinoid-based drugs?

Medicinal cannabis products which are not approved in Australia or listed on the ARTG may be accessed by Australian patients through alternate pathways. Any registered medical doctor in Australia can prescribe and apply for access for their patient if they consider medicinal cannabis the appropriate treatment.

Special Access Scheme (SAS)

The Special Access Scheme (SAS) allows prescribers (including nurse practitioners) to prescribe medicinal cannabis products for a single patient on a case-by-case basis. There are two pathways within this system:

• SAS Category A - notification pathway allowing registered medical practitioners to access and prescribe an unapproved medicinal cannabis product for a patient who is seriously ill. Prescribers must import medicinal cannabis products on a patient-by-patient basis via application to the Office of Drug Control.
• SAS Category B - application pathway through which a registered health practitioner may apply to the TGA for approval to prescribe an unapproved medicinal cannabis product for a patient under their care. The applicant must provide a suitable clinical justification for the use of the therapeutic good, including reasons why products included in the ARTG are not suitable for the treatment of the patient.

Authorized Prescriber Scheme (AP)

The TGA can grant a medical practitioner authority to prescribe a specified unapproved medicinal cannabis product for a particular indication to a class of patients in their immediate care. Any registered medical practitioner can become an AP. The medical practitioner must obtain approval from a Human Research Ethics Committee or endorsement from an appropriate specialist college unless the selected medicine's active ingredient category, dosage form, and indication are included in the TGA's “List of medicinal cannabis medicines with established history of use”. APs do not need to notify the TGA each time they prescribe the product within the approval period (up to 5 years) but they must report the number of patients they treat every six months.

Unapproved medicinal cannabis products are classified according to the Poisons Standard as Schedule 4 (Prescription Only Medicine) or Schedule 8 (Controlled Drug). As such, none are available without a prescription from a registered medical/health practitioner. The products are also categorized according to their active ingredients (see Table 1). No additional active ingredients are permitted. 

Table 1 - Categorization of Unapproved Medicinal Cannabis Products

All unapproved medicinal cannabis products imported into and supplied or manufactured in Australia must comply with the current Therapeutic Goods (Standard for Medicinal Cannabis) (TGO 93) Order 2017.

https://www.legislation.gov.au/Details/F2022C01204/Html/Text

This includes both ingredients and finished products. TGO 93 specifies the minimum quality requirements for medicinal cannabis products. The current TGO 93 does not permit the use of synthetic cannabinoids. 

Advertisement of medicinal cannabis products to consumers is illegal.

1.1.7 Any other point of relevance, if any.

All medicinal cannabis products, either approved or unapproved, but which are imported into Australia must be able to demonstrate compliance with TGO 93. A summary of the information required is provided below and a guideline has been published by the TGA to assist with conformance (reference 5).

Key points of relevance to cannabinoid ingredients are: 

• Compliance with European Pharmacopoeia monographs
  • Pharmaceutical Preparations (2619)
  • Other general monographs for herbal drugs and relating to dosage forms
• Source of active ingredients and cannabinoids
  • All active ingredients must be manufactured from the cannabis plant only.
  • Cannot contain synthetic forms or cannabinoids synthesized by chemical conversion.
• Decontamination
  • Any decontamination method used to decontaminate the cannabis plant must not use ethylene dioxide and must ensure that the quality of the product is not adversely affected.
• Identification
  • Cannabis plants used in manufacture must be positively identified using each of 
    • Macroscopic examination
    • Microscopic examination
    • Chromatographic procedures
  • Methods must be suitably validated and provided for every batch.
• Adulteration
  • Medicinal cannabis products and any ingredients used for manufacture must not contain any substance that results in their adulteration.
• Tests
  • Cannabis plants used must comply with the limits in Table 2.
  • The concentration of active ingredients must be measured and within a specified range. Assay limits differ depending on the dosage form. 
  • All tests used must be appropriately validated.
• Manufacturing quality
  • Domestic manufacturers must have a TGA GMP manufacturing license.
  • Overseas manufacture must occur on sites that comply with specified GMP standards or undergo an inspection by the TGA for compliance with the PIC/S Code of GMP.
• Labeling
  • Labels should clearly differentiate between medicinal cannabis products that are based on plant material, broad-spectrum extracts, full-spectrum extracts, and isolates (of the active ingredient). Different information is required in each case and more information is required for active ingredients that are not present as isolates.
• Microbiological attributes
  • Oral dosage forms must comply with relevant acceptance criteria for microbiological quality in accordance with one of the listed Pharmacopoeias. 

Table 2 - Specified tests for cannabis plants used in the manufacture of medicinal cannabis products

Note: In accordance with the European Pharmacopoeia, the unit mg/kg is the m/m measurement equivalent to ppm.

1.1.8 Summary of main findings & implication

• CBD is not considered a narcotic in Australia. 
• There are two oral products as Rx available on the market. These are from Phyto sources. 
• One of the products is a combination of delta-9 THC with CBD (Nabiximols) and the other is only CBD (oil). 
• Other medicinal cannabis products (with CBD or other cannabinoid-based ingredients) may be accessed by Australian patients through alternative pathways as unapproved medicines.
• For any other drug product containing CBD as Rx – the Category 1 new chemical entity pathway is required with a full CTD dossier.

All medicinal cannabis products, either approved or unapproved, but which are imported into Australia must be able to demonstrate compliance with the detailed requirements of TGO 93.

1.2 Over-the-Counter Medical Use (OTC)

1.2.1 Can CBD be available as an OTC? If yes, what are the requirements?

Yes. In theory, CBD products can be made available via a pharmacy. However, no such products are available as yet in Australia. 

1.2.2 What are specific regulations to consider?

OTC products in Australia are classified according to the Poisons Standard as either: 

• Pharmacy Medicines (included in Schedule 2 of the Poisons Standard); or
• Pharmacist-only Medicines (included in Schedule 3 of the Poisons Standard)
• General Sales medicines that are not included in any of the Schedules of the Poisons Standard

From 1 February 2021, certain preparations of cannabidiol were included in Schedule 3 (Pharmacist Only Medicine) of the Poisons Standard. This opens up a pathway for products to be available from a pharmacy. This is only applicable to cannabidiol in oral, oromucosal, and sublingual preparations included in the Australian Register of Therapeutic Goods (ARTG) when:

• the cannabidiol is either plant-derived or when synthetic, only contains the (-)-CBD enantiomer; and
• the cannabidiol comprises 98% or more of the total cannabinoid content of the preparation; and
• any cannabinoids, other than cannabidiol, must be only those naturally found in cannabis and comprise 2% or less of the total cannabinoid content of the preparation of which tetrahydrocannabinol (THC) can only comprise 1% of the total cannabinoid content; and
• the maximum recommended daily dose is 150 mg or less of cannabidiol; and
• packed in blister or strip packaging or in a container fitted with a child-resistant closure; and
• in packs containing not more than 30 days’ supply; and
• for adults aged 18 years and over.

At present, there are no products on the ARTG that meet the requirements for this classification. All OTC medicines must be included on the ARTG before they can be sold in Australia.

1.2.3 Are there any quality & safety points to consider?

A full CTD Module 3 is required to support registration. Additionally, all products must comply with the Therapeutic Goods (Standard for Medicinal Cannabis) TGO 93.

https://www.legislation.gov.au/Details/F2022C01204

This includes both ingredients and finished products. TGO 93 specifies the minimum quality requirements for medicinal cannabis products. The current TGO 93 does not permit the use of synthetic cannabinoids.

1.2.4 Any other point of relevance, if any

Current regulations would not permit a product containing < 98% CBD to be registered as an OTC drug. This is not specific to any particular source.

1.2.5 Are there regulatory differences between the various sources of CBD (phyto, synthetic, biosynthetic)?

In accordance with section 8 of TGO 93, each active ingredient and any other cannabinoid that is not an active ingredient must be from the cannabis plant, and their chemical structure must not be modified or transformed in any way (including by chemical and other means). Therefore, at this time, synthetic products are prohibited in Australia.

Cannabinoid products from non-plant sources are not permitted. 

• In theory, CBD products can be available via a pharmacy, however, no such products are available as yet in Australia. 
• Only products from phyto-source are permitted.
• To be eligible for this pathway products must contain <98% CBD, with THC up to 2%.
• The registration and quality requirements are the same as for a Rx product.

1.2.6 Summary of main findings & implication

In Australia, OTC products are classified according to Schedule 3 of the Poisons Schedule. There are currently no OTC products registered on the ARTG. Whilst this offers an alternate pathway for cannabinoid products, the data requirements are similar to those for prescription medicines. Only oral, oromucosal, and sublingual preparations may be registered via this pathway and there are limitations on the nature and levels of the cannabinoids used. 

1.3 Current Regulations for Selected Minor Cannabinoids (if any)

There are currently no approved products containing the listed minor cannabinoids (e.g. Delta 9 THC, Delta 8 THC, CBN, CBC, CBL, CBG, CBDV, CBGA with THC content< 0.2). There are also no unapproved products being imported into Australia under the special access or Authorised Prescriber schemes. 

As presented in Table 1, TGA has defined specific limits for the allowable composition of cannabinoid products. Whilst these are not specific to the minor cannabinoids listed above, they are grouped by the dominant cannabinoid form. These groupings would therefore apply to the minor cannabinoids based on their origin. 

THC-containing products, or products with THC dominant groups, are considered to be controlled substances, and limits on the active component apply. 

The requirements for quality and safety for all minor cannabinoids are the same. 

Only minor cannabinoids derived from plant sources are currently allowed in Australia.

1.3.1 If the new medical entity route is the only route, please state that and provide details of the main requirements.

As described in Section 1.1.3 above, cannabinoids may only be supplied in Australia under Schedule 3 or Schedule 4 of the Poisons Schedule. A Category 1 application is required for both pathways. 

The requirements for a Category 1 application are defined below: 

https://www.tga.gov.au/how-we-regulate/supply-therapeutic-good-0/supply-prescription-medicine/application-process/prescription-medicines-registration-process

1.3.2 Summary of main findings & implication

The use of other minor cannabinoids is limited by the definitions established by TGA (see Table 1). The pathway for registration is the same as all other cannabinoids. 

2. Regulatory Landscape Evolution Over Time

TGA first introduced legislation to support the legal cultivation of cannabis for medicinal purposes in 2016. This was further supported by the introduction of legislation for the registration of medicinal cannabis products on the ARTG. Despite the introduction of these pathways, the majority of products are still used in Australia as “unapproved products” via the special access scheme or the Authorised Prescriber program. 

All approved and unapproved products must meet the requirements of TGO93 which outline the quality standards for cannabis products. Amendments to TGO 93 were made in March 2022 due to the significant increase in the supply and use of medicinal cannabis in Australia. Following a transition period for industry, from 1st July 2023 all medicinal cannabis products released for supply in Australia must conform with the changes. The major change is the requirement for GMP manufacture of medicinal cannabis products supplied in Australia. Changes have also been made to the labeling and microbiological attribute requirements, and the need for child-resistant packaging has been introduced. 

The current entry for CBD in Schedule 3 of the Poisons Standard includes synthetic and naturally derived CBD. In the event a synthetic CBD-based medicine is registered on the ARTG as an OTC medicine, the TGA expects that TGO 93 will be amended accordingly. 

It is likely that the TGA guidelines and regulatory framework will continue to evolve as more products enter the Australian market. The Australian framework currently allows for the use of minor cannabinoids but limits the levels to set groupings.