The draft Therapeutic Goods Order No. 93 (Standard for Medicinal Cannabis) foreshadows the proposed minimum quality standards for medicinal cannabis products which may be made available, subject to the appropriate approvals or authorisations, to patients in Australia under the Narcotic Drugs Act 2016 (Cth) and corresponding state legislation. Partner, Dr Teresa Nicoletti and Law Clerk, Helaena Short discuss.
On 24 November 2016 the Therapeutic Goods Administration (TGA) released the draft Therapeutic Goods Order No. 93 (Standard for Medicinal Cannabis) (draft MC Order) and corresponding draft Guidance, seeking feedback from interested parties. The draft MC Order specifies the minimum quality requirements for medicinal cannabis products (MCPs), and the ingredients used therein, to be manufactured, imported and supplied in Australia.
The draft MC Order has been made under Part 3-1 of the Therapeutic Goods Act 1989 (Cth) which provides that the Minister may mandate, among other things, minimum quality requirements, required manufacturing procedures or compliance with an existing monograph, for a therapeutic good or class of therapeutic goods.
In particular, the draft MC Order applies to both:
a) MCPs which are manufactured in Australia under the Narcotic Drugs Act 2016 (Cth); and
b) MCPS which are imported into Australia.
The draft MC Order also applies to cannabis plant material and any other ingredients, such as excipients, used in the manufacture of an MCP.
A sponsor must not import, manufacture or supply an MCP if it does not conform to the requirements set out in the MC Order (assuming it is predominantly introduced in its present form). This is significant for sponsors because locally manufactured and imported MCPs will be subject to the same mandatory quality standards despite imported products falling outside the general provisions of the Narcotic Drugs Act 2016 (Cth) and Narcotic Drugs Regulation 2016.
The specific requirements set out in the draft MC Order are fivefold.
- Firstly, all active ingredients used in an MCP must be derived from a cannabis plant only. Notably, this precludes the use of synthetic dronabinol or other synthetic cannabinoids and other herbal active ingredients and pharmaceutical active ingredients which are not derived from the cannabis plant.
- Secondly, where cannabis plant material used in the manufacture of an MCP is subjected to a decontaminating treatment (e.g. gamma irradiation to reduce the microbial load) the sponsor must demonstrate that the treatment does not adversely affect the quality of the MCP.
- Thirdly, all cannabis plant material used in the manufacture of an MCP must be subjected to a battery of identification tests to identify potential adulterants and substitutes. Adulteration of an MCP, or any ingredient(s) used therein, is prohibited in all circumstances. The battery of tests must include the following types of tests:
a. macroscopic examination;
b. microscopic examination; and
c. chromatographic procedures (e.g. high-performance liquid chromatography, thin-layer chromatography, and gas chromatography).
- Fourthly, all cannabis plant material used in the manufacture of an MCP must be subjected to appropriate tests from the European Pharmacopoeia (EP) to assess the concentration of potential toxic contaminants (aflatoxins, ochratoxin A, heavy metals and pesticides) in addition to tests for foreign matter, loss on drying and total ash.
- Finally, each active ingredient (including any corresponding acid) in a representative sample of a finished MCP must satisfy the assay limits specified in the draft MC Order. Any cannabinoid present in a quantity or proportion greater than or equal to 1.0% w/w or w/v of an MCP is taken to be an ‘active ingredient’. The assay limit is different for different final dosage forms and is assessed by reference to the ‘stated content’ of each ingredient - being the amount stated on the MCP label or otherwise articulated to the ODC. The assay limits are specified as follows:
Dosage form Example Assay Limit
Herbal sachet of cannabis plant material 80.0-120.0%
Tablets or capsules - 90.0-110.0%
Other oromucosal spray 90.0-110.0%
In addition to the abovementioned requirements, the draft MC Order also incorporates, to the extent that it is not inconsistent, the general EP monograph entitled Pharmaceutical Preparations. Furthermore, other Therapeutic Goods Orders may also apply to an MCP, e.g. Order 77 (for finished products) or Order 78 (for tablets and capsules).
Importantly, the requirements set out in the draft MC Order are not comprehensive requirements but rather minimum requirements which apply throughout the entire shelf life of an MCP. In particular, the TGA recommends that a prudent manufacturer will apply release specifications that are more exacting than those included in the draft MC Order, to ensure compliance with the prescribed assay limits.
Sponsors of MCPs should note that quality and other requirements applicable to MCPs in Australia are numerous and varied and are not restricted to those set out in the draft MC Order. Sponsors, being ultimately responsible for an MCP, should be particularly familiar with all of the legal and regulatory requirements. Stakeholders who are interested in responding to the draft MC Order and corresponding Guidance can do so before 16 January 2017 by using the online form on the TGA’s website or posting a hardcopy submission to the Experimental Products Section of the TGA.