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Notice of interim decisions on proposed amendments to the Poisons Standard - ACMS and Joint ACMS-ACCS meetings, June 2020
Scheduling of chemicals and poisons
4.1 Cannabidiol (private application) and cannabidiol (delegate initiated)
4 Interim decisions on proposed amendments referred to the Advisory Committee on Medicines and Chemicals Scheduling in joint session (Joint ACMS-ACCS #25, June 2020)
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4.1 Interim decision in relation to cannabidiol (private application) and cannabidiol (delegate initiated)
Pursuant to regulation 42ZCZN of the Regulations, a Delegate of the Secretary has, in relation to the proposed amendments to cannabadiol made the following interim decisions:
- in relation to the proposed amendment in the private scheduling application, made an interim decision not to amend the current Poisons Standard to exclude cannabadiol from scheduling and allow its general sale.
- in relation to the proposed delegate-initiated amendment, made an interim decision to amend the current Poisons Standard to down schedule cannabadiol to allow greater access through a new Schedule 3 entry in accordance with specified requirements and with additional supply requirements specified in Appendix M to allow it to be provided by a pharmacist.
The proposed Poisons Standard entry in relation to cannabidiol is as follows:
Schedule 4 - Amend Entry
CANNABIDIOL in preparations for therapeutic use where:
- cannabidiol comprises 98 per cent 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 per cent or less of the total cannabinoid content of the preparation;
Schedule 3 - New Entry
Appendix F, Part 3 - New Entry
POISONS (other than agricultural and veterinary chemicals) TO BE LABELLED WITH WARNING STATEMENTS OR SAFETY DIRECTIONS
|POISON||WARNING STATEMENTS||SAFETY DIRECTION|
67: Do not use if pregnant or likely to become pregnant.
Appendix M - New entry
ADDITIONAL CONTROLS OR SUPPLY REQUIREMENTS FOR POISONS INCLUDED IN SCHEDULE 3 TO ALLOW THEM TO BE PROVIDED BY A PHARMACIST
|POISON||CONDITION OF SUPPLY|
In making these interim decisions, the Delegate considered the following material:
- The private scheduling application and delegate-initiated amendment to amend the current Poisons Standard with respect to cannabidiol;
- The 5409 public submissions received in response to the pre-meeting consultation under regulation 42ZCZK of the Regulations;
- The advice received from the Advisory Committee on Medicines and Chemicals Scheduling in joint session (Joint ACMS-ACCS #25);
- Subsection 52E(1) of the Therapeutic Goods Act 1989, in particular (a) the risks and benefits of the use of a substance; (b) the purposes for which a substance is to be used and the extent of use of a substance; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; (e) the potential for abuse of a substance; and (f) any other matters considered necessary to protect public health;
- The Australian Health Ministers' Advisory Council's Scheduling Policy Framework (SPF 2018);
- The Scheduling handbook: Guidance for amending the Poisons Standard;
- The TGA Review on the safety of low dose cannabidiol; and
- An external expert evaluation (pdf,281kb) of the private application.
Summary of Joint ACMS-ACCS advice to the Delegate
The Committee recommended that the current scheduling of cannabidiol remains appropriate. The majority of the members on the Committee were not persuaded that there is currently sufficient evidence to relax the access controls on cannabidiol, derived from plants or synthetically produced, to the general sales levels or that cannabidiol meets the scheduling factors for Schedule 3.
Members agreed that the relevant matters under Section 52E(1) of the Therapeutic Goods Act 1989 included (a) the risks and benefits of the use of a substance; (b) the purpose for which a substance is to be used and the and extent of use of a substance; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; (e) the potential for abuse of a substance; and (f) any other matters that the Secretary considers necessary to protect public health.
The reasons for the advice included:
a - the risks and benefits of the use of a substance:
The Committee identified the following risks:
- CBD, being an inhibitor of CYP3A4, CYP2D6, CYP2C19, CYP2C9 and P-glycoprotein, is likely to have interactions with many pharmaceuticals available for human use. Pharmacodynamic interactions with drugs that cause CNS depression (opioids, benzodiazepines, antipsychotics, gabapentinoids, sedating antihistamines), are likely.
- CBD can have adverse reactions including somnolence, decreased appetite, diarrhoea, fatigue and liver dysfunction.
- The current lack of approved indications would prevent a pharmacist being able to determine appropriate supply.
- The Committee noted the potential for use, outside of that legally permitted by the Poisons Standard, particularly in children/adolescents, if CBD were to be available as a Schedule 3 medicine.
- The Committee noted that it was difficult to assess the benefits in the absence of an approved product or clearly defined indications.
- The Committee noted that the TGA Safety Review concluded that doses up to 60 mg/day may potentially be used safely in adults.
b - the purposes for which a substance is to be used and the extent of use of a substance:
- The Committee noted that currently there are no registered CBD products in Australia and unapproved CBD products are accessed via the Special Access Scheme (SAS).
- The pre-meeting public submissions put forward a wide range of conditions for which CBD could be used, of which some were consistent with a Schedule 4 listing and some may be appropriate under a Schedule 3 classification.
c - the toxicity of a substance:
- The Committee agreed that CBD toxicity is likely to be lower at low doses.
- The Committee identified that there is potential to increase risk of toxicity from other drugs through inhibition of their metabolism/efflux.
d - the dosage, formulation, labelling, packaging and presentation of a substance:
- The Committee noted there is no registered product available in Australia, however overseas experience indicates a broad range of presentations including orally, topically, via inhalation and vaporisation.
e - the potential for abuse of a substance:
- The Committee acknowledged that CBD has low abuse potential at low doses.
- There is a possible risk of overuse or misuse of low dose CBD for inappropriate indications including the treatment of children.
f - any other matters considered necessary to protect public health:
- In the absence of an Australian registered product, the Committee considered that down scheduling may not be effective at improving consumer access to low dose CBD, simultaneously noting that down-scheduling may encourage sponsors to apply for registration.
- The safety and quality of a pharmacist compounded CBD product would be difficult to ensure or enforce. There was also concern that without a defined indication and guidance, compounding pharmacies may have difficulty ensuring that dispensing was consistent with the Schedule 3 factors.
- The Committee raised concerns regarding the use of low dose CBD in pregnancy or lactation advising that the risks are unknown as these aspects were not reviewed in the TGA safety report.
Reasons for the interim decisions (including findings on material questions of fact)
I have made interim decisions, firstly not to exempt CBD from inclusion in the Poisons Standard and, secondly, to facilitate greater access to cannabidiol (CBD) by down-scheduling it from Schedule 4 to Schedule 3 of the Poisons Standard, subject to a number of criteria being satisfied.
The two interim decisions are represented collectively in one proposed amendment to the Poisons Standard.
The aforementioned criteria required to be satisfied are as follows:
- restrictions on the preparation and dose, dosage form, pack size, age and limiting supply to Australian registered products
- a requirement for a child-resistant closure unless the product is packed in blister or strip packaging
- creation of an Appendix F listing to include a requirement for specific warning statements on the labelling of CBD-containing Schedule 3 products available to the public
- exclusion of a medicine including CBD from Appendix H, that is those medicines are excluded from being advertised directly to consumers
- creation of an Appendix M listing to limit supply to medicines including CBD which are entered on the Australian Register of Therapeutic Goods.
However, as part of my interim decisions, I am seeking additional advice from the November meeting of the Joint ACMS-ACCS, on the following criteria that I have incorporated:
- An Appendix M entry to limit supply to medicines entered in the Australian Register of Therapeutic Goods (ARTG);
- Dose restrictions;
- Age restrictions; and
- Advertising restrictions.
With criteria in place to limit supply to ARTG registered products, I am of the the view that CBD meets the Schedule 3 Scheduling Factors as outlined in the SPF 2018 as follows:
- the medicine is substantially safe with pharmacist intervention to ensure the quality use of the medicine. There may be potential for harm if used inappropriately.
- the use of the medicine is not expected to produce dependency.
- the risk profile of the medicine is well defined (at the proposed dose). The risk factors for adverse effects, interactions and contraindications are known, identifiable and manageable by a pharmacist (when in preparations for therapeutic use and packaged in containers with child-resistant closures.)
The detailed reasons for my decision follow.
Having considered the proposal to exempt CBD from scheduling in the private application and the findings of the expert evaluation, I am not satisfied that CBD can be supplied at the general sales level, with reasonable safety, and without any access to health professional advice. The external evaluation report found that whilst CBD has low toxicity, adverse events and drug interactions are possible. On that basis, it is my firm view that CBD is unsuitable for general sales. It is my view that consumers would not be able to identify and self-manage the conditions for which CBD would be most commonly used without guidance from a health professional. Due to uncertainty of adverse effects, the effects of longer term use and the potential for drug interactions, I find that the risks cannot be managed with packaging and labelling in the absence of pharmacist advice. I note that there was unanimous agreement, among the Joint ACMS-ACCS #25 members, in their advice on this matter, that CBD did not meet the criteria for 'reasonable safety' as defined in the Scheduling Policy Handbook.
I have considered the concerns raised by the Joint ACMS-ACCS #25 in down-scheduling CBD from Schedule 4 to Schedule 3. I understand that in the absence of a registered product or a specific indication, it is difficult to assess the risks and benefits of over the counter (OTC) use. Accordingly, I have applied criteria in the entry in Schedule 3 as earlier noted as well as new entries in Appendices F and M that would address these issues. I have also excluded medicines including CBD from an entry in Appendix H, that is from being advertised directly to consumers.
I note the concerns raised in the external evaluation report over the paucity of evidence of efficacy for many of the indications for which there is public demand. However, the restrictions that I have applied in Appendix M should appropriately manage these concerns.
Furthermore, in accordance with the availability of poisons as outlined in the Poisons Standard, the inclusion of a poison in a Schedule indicates the degree of control required if it is marketed. It does not indicate that:
- the poison is available; nor
- the poison has been approved or is efficacious for any use that may be specified in a Schedule; nor
- any obligation for registration of a therapeutic good containing that poison is negated.
I note that if a CBD product were to be registered as a Schedule 3 medicine, an application for product registration would include a full submission to support its intended use, including data relating to the efficacy for any indications for the product. The TGA product evaluation process would include assessment as to whether the proposed use was consistent with a Schedule 3 listing (i.e. self-diagnosable or requiring pharmacist intervention to monitor safe use following initial medical diagnosis).
I have decided to limit the proposed Schedule 3 entry to oral, oral mucosal and sublingual formulations. In making this decision I have attached weight to the findings of the TGA Review on the safety of low dose cannabidiol. The report establishes that doses up to 60 mg/day may have a suitable safety profile and possible clinical utility when used via the oral route, in the management of some conditions that do not require medical practitioner oversight. I am of the view that this is a necessary limitation to protect public safety, based on the current available evidence.
I have identified the risk of accidental exposure to children particularly for liquid formulations containing CBD. On that basis, I have decided to introduce a requirement in the Schedule 3 entry for the inclusion of child resistant closures, unless the product is packed in blister or strip packaging.
The Scheduling Policy Framework (SPF 2018) provides that the advertising of medicines containing Schedule 3 substances should be permitted unless there is reason not to. In order for these medicines to be lawfully advertised, they need to be included in Appendix H of the Poisons Standard. Having considered the matters set out in the Guidelines for advertisements for medicines containing Schedule 3 substances, I have considered the potential impact on public health in accordance with the questions noted as relevant to the delegate's considerations in those Guidelines. In particular, I have had regard to the potential for drug-drug interactions the risk of occurring of which may be increased by advertising. I also consider that increased patient education is required to ensure safe use and that patient choice could therefore be adversely influenced if CBD products were to be advertised. I have not taken into account any other additional factors Accordingly, I have decided not to list CBD in Appendix H.
I have also decided to include a new Appendix M entry for CBD, which would restrict the supply of CBD to medicines entered on the Australian Register of Therapeutic Goods (ARTG). This will ensure that only products that have been approved for a specific indication appropriate under a Schedule 3 listing, will be available without a prescription. I note the Committees' advice that the safety and quality of a compounded CBD product is difficult to ensure and enforce. It is my view that this measure will enable pharmacists to make informed decisions to supply CBD in line with Schedule 3 factors and in accordance with professional practice standards.
I note that the TGA Review on the safety of low dose cannabidiol did not assess the use of CBD during pregnancy and lactation. For this reason, I have decided to include a new entry in Appendix F, that is a requirement for warnings against the use of Schedule 3 CBD in pregnancy and breastfeeding.
I have had regard to the 5409 public submissions received in the pre-meeting consultation and the diversity of views expressed in these submissions. There was a large volume of submissions from individuals as part of a campaign. The majority of these submissions (approx. 52%) supported an alternative proposal set out in the campaign and just under half (46%) agreed with the private application, while a small number (approx. 2.5%) agreed with the delegates proposal. Of the 109 non campaign submissions, 80% of submission supported the down scheduling of CBD in some form. Many proposed a new solution and alternative means to increase accessibility while still balancing public safety.
I will consider the Committees' advice and the submissions received in response to my interim decision, before coming to a final decision on the scheduling of CBD.
Proposed implementation date
1 June 2021