Since last week, Australian patients have officially been permitted to purchase low-dose cannabidiol (CBD) over the counter from a pharmacist without a doctor’s prescription.
Australia’s drug regulator, the Therapeutic Goods Administration (TGA), gave the go-ahead from 1 February, upping the daily dosage limit from its interim decision last year of 60mg to 150mg per day.
While this is expected to have a positive impact on many patients’ lives, there are myths circulating about this development that require clarification.
According to the Medical Cannabis Research Collaboration (MCRC), Cannvalate’s research division, a major misconception is that products are available to buy right now – but in reality, consumers could be waiting a year or more.
Reclassifying CBD medicines
Small Caps first reported the TGA’s interim decision to down-schedule certain CBD products in September from Schedule 4 (prescription medicine) to Schedule 3 (pharmacist-only medicine) of the Poisons Standard.
This means companies could apply to register their applicable products to be available through a pharmacist, without the need for a prescription.
In December, the TGA finalised its decision and increased the dosage limit to a maximum of 150mg per day following further consideration of safety information, public submissions on the interim decision and the advice of advisory committees. The scheduling amendment came into effect on 1 February.
Rumours have since been circulating that CBD products are expected to be available over-the-counter straight away, or at least sometime in 2021.
However, meeting the TGA’s criteria for Schedule 3 over-the-counter status will “not be easy”, according to Cannvalate chief growth officer Julian Azzopardi.
“Most products are currently lacking the clinical data required to meet stringent TGA safety, efficacy and quality standards,” he told Small Caps.
“Registering a CBD product on the TGA register is not automatic and requires strong clinical data including phase I, II and III clinical trials. Once the data has been collected and the dossier is submitted to the TGA, there is a TGA evaluation timeline of approximately six months.”
“You could expect to find CBD available in your pharmacies in 2022,” Mr Azzopardi said.
Product registration can be a lengthy process
Ordinarily, the timeline for conducting clinical research to register a product with any global regulatory body is a lengthy process that can take several years.
The Australian New Zealand Clinical Trials Registry (ANZCTR), an online registry of clinical trials being undertaken, shows very few trials are currently underway investigating cannabinoids that could relate to a Schedule 3 registration program.
The expectation from a regulatory body to register a product is that safety, quality and efficacy targets are met.
Safety is partly evidenced by conducting toxicology studies in two animal species. However, the TGA have already assessed low-dose CBD as a safe ingredient, hence down-scheduling it from prescription-only to an over-the-counter product.
Efficacy targets need to be met using the manufacturer’s final dose form and the correct concentration. Evidencing that the CBD product performs well for a given medical indication is critical; for example, a CBD pain medication will need to lower a patient’s visual analogue score (a most commonly used measure of pain intensity in pain research) by 33%.
The 150mg concentration was only confirmed by the TGA in mid-December 2020, which means manufacturers were limited to finalising their clinical trial program until this final decision.
To assure the quality of the product meets appropriate standards and is consistent, a highly detailed chemistry, manufacturing and controls (CMC) dossier is mandatory.
However, there may be viability in a partial literature-based submission for some of the evidence required, which would enable an accelerated pathway.
“Now that the TGA has given clarity about the level of clinical justification required to register an S3 product, it will be 12 months or more before any company meets the TGA S3 criteria for registration,” Cannvalate chief executive officer Dr Sud Agarwal told Small Caps.
“The Australian media and some ASX-listed companies, perhaps unwittingly, misdirected the public into believing members of the public could now walk into a pharmacy and purchase CBD without a prescription,” he said.
Although Mr Azzopardi, who leads Cannvalate’s Medical Cannabis Research Centre, did admit that political pressure could be a motivation for the TGA to expedite its usual approval timeframe – in which case, this could change forecasts.
“But for now, 12 months or more is accurate,” he said.
Preparing for registration
Mr Azzopardi said the approach of the MCRC to register a Schedule 3 product involves preparing a comprehensive submission to the TGA detailing the proposed pathway and requesting validation.
The pathway will cover the proposed methods of evidencing the required safety, efficacy and quality criteria.
“We’re currently supporting four companies for registering one or more Schedule 3 CBD products and we look forward to unmasking the new regulations as each stage is crossed,” he said.
According to the Oceania Cannabis Report, produced by London-based advisory group Prohibition Partners, the Australian medical cannabis market is estimated to be worth up to $1.3 billion by 2028.
Mr Azzopardi said the MCRC has received multiple inquiries from local and international organisations hoping to secure market share in Australian over-the-counter CBD sales.
“We have received Human Research Ethics Committee (HREC) approval to commence clinical trials for two sponsors creating S3 CBD products, with additional programs expected to soon be approved. Given our medicinal cannabis specialisation, this is a very exciting space for us,” he said.
Cannvalate currently serves about 40-50% of Australia’s medical cannabis patients through its prescription network.