TGA seeking advice from the Scheduling Committee this November 9 min read
The Therapeutics Goods Administration (TGA) is proposing amendments to the Poisons Standard which, if made, will permit pharmacists to sell low-dose cannabidiol (CBD) products to adults without a prescription.
If such products can get registered on the Australian Register of Therapeutic Goods (ARTG), this has the potential to achieve the intended effect of accelerating patient access to medicinal cannabis products in Australia and growing this high potential market. However, the current dearth of registered cannabidiol (CBD) products is a barrier which the proposed amendments may not overcome. In seeking additional advice from the Joint Advisory Committee on Medicines and Chemicals Scheduling (Scheduling Committee) this November before making its highly anticipated final decision, the TGA is attempting to bridge the divide between increasing access to CBD, and addressing the safety concerns that initially saw the Scheduling Committee recommend maintaining the status quo.
Businesses intending to import, manufacture and supply cannabis products in the Australian market should monitor these developments closely, especially given their potential impact on product development and the pre-clinical and clinical trial data required to support an ARTG application if ultimately required.
- If more CBD products can achieve ARTG registration, the proposal to down-schedule CBD from Schedule 4 (prescription medicines) to Schedule 3 (pharmacist medicines) has the potential to increase patient access to CBD products.
- The Scheduling Committee initially advised the TGA that the current scheduling of CBD is appropriate, but recognised that in the absence of increasing ARTG registrations, down-scheduling CBD may not be effective to improve access to low dose CBD.
- Schedule 3 CBD products will still need to meet stringent requirements for ARTG registration, including that the product demonstrates efficacy for the indication for which registration is sought.
- Several manufacturers have raised doubts that the efficacy requirement can be satisfied in light of the low-dosage restrictions accompanying the proposal to move CBD from Schedule 4 to Schedule 3.
- Whether the down-scheduling can actually serve to increase patient access to CBD products will in part depend on whether the TGA can strike the right balance between the traditional pillars which underpin ARTG registration: safety and efficacy.
Australian and foreign cannabis and pharmaceutical companies seeking to enter the Australian cannabis market through the manufacture, import or supply of cannabis products.
In Australia, laws permitting the cultivation, production, manufacture and research of medicinal cannabis came into effect in 2016 through a complex licence and permit framework regulated at federal, state and territory levels.
Cannabis is on Schedule 8 of the Commonwealth Poisons Standard as a controlled substance. CBD for therapeutic use is on Schedule 4 where the cannabinoid content, a group of closely related compounds, comprises ≥98% of CBD (a type of cannabinoid) and ≤ 2% of any other naturally occurring cannabinoids.
Schedule 4 CBD products are only available on prescription from an Australian-registered medical practitioner. ARTG registration is a pre-condition to prescription. This requires demonstrated evidence of clinical efficacy for the intended use, as well as safety and quality. However, with only two registered cannabis products – GW's Pharma's Savitex nabaximols product (for multiple sclerosis), and now GW Pharma's Epidyolex CBD product (for seizure therapy) only just registered in September 2020 – patient access to medicinal cannabis through this pathway is extremely limited at present.
Schedule 8 unapproved cannabis products can only be accessed by the Special Access Scheme (SAS), Authorised Prescriber scheme or clinical trials. Unless the patient is seriously ill, clinicians applying for TGA permission to use the SAS pathway to prescribe medicinal cannabis must demonstrate that all options for conventional treatment have been exhausted.
CBD products should not be confused with hemp products and fibres, which are regulated at state level rather than federally, and cannabis sativa seeds used as an ingredient in foods and which are regulated by the Foods Standard.
Following a public consultation, the TGA recently released an interim decision to amend Schedule 3 of the current Poisons Standard to include low-dose CBD. If implemented, this would permit the sale of oral, oral mucosal and sublingual (under the tongue) CBD formulations to adults without a prescription which satisfy the following criteria:
- the CBD is plant derived, or when synthetic only, contains the (-) CBD enantiomer;
- the maximum recommended daily dose of the product is ≤ 60mg of CBD;
- supply is in packs containing not more than 30 days' supply;
- the cannabinoid content comprises ≥98% CBD and ≤2% of other naturally occurring cannabinoids; and
- the product is packed in a blister or strip packaging or in a container fitted with a child-resistant closure.
Other formulations such as gels, oils or vaporised products would be excluded.
Down-scheduling CBD products which meet the above criteria from Schedule 4 to 3 removes the need for a prescription. They could be sold by a pharmacist who must assess appropriate use – similar to the sale of other Schedule 3 drugs such as Ventolin and certain cold and flu preparations.
Supply of CBD products meeting the TGA recommended criteria would still need to be registered on the ARTG and approved for a specific indication. This means they would still need to undergo a pre-market assessment of safety, efficacy and quality, and once approved must be labelled with specific warning statements and may not be advertised directly to consumers.
Registration on the ARTG is to be contrasted with listing on the ARTG. Listed medicines are assessed by the TGA for quality and safety but not efficacy. CBD products can only be eligible for listing rather than registration if CBD is included in a determination of permissible ingredients for that purpose, and presently it is not.
Impetus for change
A Senate Inquiry report, handed down on 26 March 2020, recognised that the current regulatory regime creates hurdles to bringing products to market and prevents patient access to medicinal cannabis in Australia. Following recommendations from the Senate Inquiry, the TGA conducted a public consultation, receiving significant interest with more than 5,400 submissions, before making its interim decision.
The TGA interim decision to down-schedule CBD was supported in some form by 80% of the 109 non-campaign submissions. The remaining campaign submissions were approximately evenly split in their support for an alternative proposal, or to de-schedule CBD altogether. While the TGA's rationale is to increase patient access to CBD products, if implemented, this would also better align Australia more closely with its international counterparts. These include the United Kingdom, Canada, Switzerland and some states in the United States, where some CBD products are sold over the counter without a prescription
Addressing the Scheduling Committee's concerns
In making its interim decision, the TGA had regard to the Scheduling Committee's advice, as required under the Therapeutic Goods Act 1989. The Scheduling Committee was of the view that the current scheduling of CBD remains appropriate, citing a number of reasons including the risk that the current lack of approved indications would prevent a pharmacist being able to determine appropriate supply, and that the safety and quality of a pharmacist-compounded CBD product would be difficult to ensure or enforce.
The TGA's interim decision introduces additional requirements which seek to address the Scheduling Committee's concerns. Schedule 3, unlike Schedule 4 (for prescription medicines), does not mandate ARTG registration, However, a key safeguard in the TGA's decision is that down-scheduled CBD products would still be required to be registered on the ARTG. This would ensure that such CBD products will still be assessed for safety, quality and efficacy, and that only those products which have been approved for a specific indication will be available without a prescription.
Overcoming the current barriers to increase access
Whilst the TGA's interim decision seeks to address the Scheduling Committee's safety concerns, it does not address the fact that a key barrier to accessing CBD products is the lack of products registered on the ARTG. This is recognised in the Senate Inquiry report.
Under Schedule 4, no dosage restrictions are presently imposed on CBD products. Under the proposed Schedule 3, a low-dose restriction would be imposed. This is based on the TGA's safety findings that CBD presents a good safety and tolerability profile at a low-dose range of under 60mg/day and may have possible clinical utility when used via the oral route.
In the course of the TGA public consultation, some manufacturers submitted that the current lack of evidence as to the therapeutic value of CBD products at this low-dose may not satisfy the efficacy requirement for ARTG registration, and would therefore not address this key barrier which is currently preventing products coming to market.
The Scheduling Committee itself, despite advising that the current scheduling of CBD remains appropriate, noted that in the absence of registered products, down-scheduling CBD may not be effective at improving access to low dose CBD.
Other manufactures have said that the ARTG registration requirements should not be relaxed in relation to medicinal cannabis products, and support maximum dosage requirements pending further clinical evaluation before medicines are approved.
Despite diverging views, it nevertheless seems that the ARTG registration criteria - currently recognised as posing regulatory hurdles for Schedule 4 products, would not only persist in relation to Schedule 3, but could be elevated by reason of the accompanying dosage restrictions. If so, despite the TGA's intention, down-scheduling CBD to Schedule 3 may not have the effect, or at least the immediate effect, of facilitating greater patient access to CBD products and opening the market to these consumers.
As Australia's cannabis market is still in its infancy, this conundrum may be answered over time as the numerous clinical trials for medicinal cannabis products that are currently underway show hoped-for results, with the expectation that there will be more applications for ARTG registration, which will in time mean more products are available to patients.
The public was invited to make further comment by mid-October 2020. However, with the volume of submissions already considered by the TGA, it seems more likely that any change to the TGA's interim decision would be on the basis of the additional advice it is now seeking from the Scheduling Committee this November on the additional restrictions around age, labelling and dosage that would accompany any down-scheduling.
The down-scheduling CBD from Schedule 4 to 3 would have the obvious advantage of permitting access to safe, low-dose CBD products without the need for a prescription. The next challenge is to have ARTG-registered CBD products available to consumers. These additional restrictions may address ongoing safety concerns, but if CBD products proposed to be sold as pharmacist medicines are limited to low-dosage formulations, they may still be out of reach to consumers. If such products cannot demonstrate the requisite degree of efficacy, they will not achieve the ARTG registration. Therefore, the down-scheduling CBD may merely create further regulatory hurdles without increasing patient access to CBD products.
Any move of CBD to Schedule 3 is expected to occur in June 2021. Businesses intending to import, manufacture and supply cannabis products in the Australian market should consider how the criteria imposed will impact product development, and the pre-clinical and clinical trial data required to support an ARTG application if ultimately required.
The TGA's final decision will be closely monitored and we will keep you updated.