The Regulatory Affairs Professionals Society reports…
The framework for regulating cannabis as a pharmaceutical product varies widely across the world, though increased clinical research into cannabis products means more approvals are likely under any scenario.
“It’s currently a complex patchwork of approaches,” Michael Craig, a principal consultant at Parexel International, said during a session on cannabis regulatory challenges and harmonization at RAPS 2020 Convergence. “That is the embodiment of it being borne out by national legislation rather than an overarching EU or European Medicines Agency framework.”
Though Craig was speaking specifically of the approaches within the European Union, the same is true in the United States, where states are passing medical marijuana legislation independent of federal action. Additionally, Canada has its own regulatory framework for defining and governing medicinal cannabis products.
Under international drug control treaties, the use of cannabis in the European Union is limited to scientific and medical purposes, and medicines are authorized through a number of different procedures. Also, individual member states have different schemes for allowing patients to access unapproved medicines under medical supervision, according to Craig.
“Europe has seen a lot of harmonization,” Craig said. “However, for cannabis and medicinal products, most of the legislation is at a national level and that really results in quite a diverse and country-specific landscape, as opposed to a homogenous EU-wide one.”
Under the current EU regulatory landscape, medicinal cannabis can go through one of three pathways. To become a licensed medicine, products must go through a Marketing Authorisation Application (MMA) process, which requires drug sponsors to demonstrate quality, safety and efficacy. Products can also be accessed under the compassionate/exceptional use process. This process may be used for magistral or extemporaneous products – classifications akin to compounded product — which must be prescribed by a specialist on a named patient basis. The third pathway is an expanded use scheme, which is specifically for patients with unmet clinical needs to allow them to access to medicines still in development.
Meanwhile, EU member states have enacted various pieces of legislation to legalize medicinal cannabis use, with the Netherlands leading the way in 2003 and Ireland not passing legislation until 2019.
“It’s almost like a domino effect whereby one country might legalize and then other countries will see that there hasn’t been any negative consequences… and they all follow suit,” Craig said.
There are also numerous clinical trials underway. As of August 2020, there were 30 ongoing clinical trials in Europe.
But many regulatory challenges remain, Craig said, including determining who can prescribe these medicines, how prescribing guidelines will be updated, and how patients will be monitored.
US regulatory framework
Currently in the United States, 33 states, including the District of Columbia, have legalized medical marijuana and 10 states, including the District of Columbia, have legalized recreational use. These laws contradict US federal law, where cannabis and CBD are considered a schedule I substance by the US Drug Enforcement Administration, according to John Joines, senior manager for regulatory affairs at PPD, who reviewed the U.S. regulatory environment.
“The concern with all these various state approvals and other things is really the quality and the consistency,” Joines said.
The Farm Bill of 2018 removed cannabis and cannabis derivatives with very low THC content from the definition of marijuana in the Controlled Substances Act. If cannabis is going to marketed as having a therapeutic effect it must be approved by the US Food and Drug Administration for safety and efficacy. Dietary supplements go through a separate process and it is illegal to have a food supplement with CBD added or to market CBD as a dietary supplement, Joines said.
In July 2020, the US Food and Drug Administration issued draft guidance for industry on clinical research into cannabis and cannabis-derived compounds. Cannabis under the 0.3% delta-9 THC limit may be used for clinical research, according to the guidance. “The release of this guidance, as well as the Farm Bill Act in 2018, has really opened up the field for additional research and development,” noted Joines. (RELATED: Cannabis clinical research clarified in draft guidance, Regulatory Focus 22 July 2020)
The significant future challenges for the development of pharmaceutical cannabis in the US are mainly related to manufacturing and clinical trials, Joines said.
In Canada today, health products containing cannabis or for use with cannabis are regulated under the Cannabis Act and the Food and Drug Act. Under this framework, products made from cannabis or hemp plants can be classified as a Natural Health Product (NHP) or a drug.
To be classified as an NHP, products can only contain cannabis parts which either do not meet the definition of cannabis in the Cannabis Act, or that have been exempted from the Cannabis Act through the Industrial Hemp Regulations. The permitted parts of the plant can contain no more than 10 ppm THC, and no isolated or concentrated phytocannabinoid. These products are not subject to the Cannabis Act’s restrictions.
Cannabis products containing ingredients and percentages of the plant that are above what is allowed for NHP are classified as a drug. In this case, clinical safety and efficacy must be demonstrated, according to Ahmed Abouelnour, senior specialist for regulatory affairs at Medicago, who reviewed the Canadian regulatory environment and moderated the session.
Abouelnour predicted that in the future Canada is likely to regulate cannabis based on its phytocannabinoid potency, dividing it into prescription medicines (variable potency), over-the-counter products (low potency), and nutraceutical products (non-psychoactive ingredients).