7. Regulating the product

Introduction

  1. 7.1 This chapter considers the question of which products should be supplied under a Victorian medicinal cannabis scheme, assuming that they are produced under arrangements set out in Chapter 6.
  2. 7.2 These products would need to be quality controlled and available in therapeutically appropriate forms. In this regard, one of the Commission’s recommended regulatory objectives is that the any Victorian medicinal cannabis scheme ought to ‘ensure that medicinal cannabis products are of reliable quality and known composition’.1
  3. 7.3 Several submissions received by the Commission endorsed this objective.2 The Australian Nursing & Midwifery Federation (Victorian Branch) expressed its support for ‘a clear legislative and regulatory framework to ensure quality, efficacy and reliability of the end product’, which it said is ‘necessary for the protection of patients’.3
  4. 7.4 In a joint submission to the Senate Legal and Constitutional Affairs Committee’s inquiry into the Regulator of Medicinal Cannabis Bill, cannabis researchers from the University of Sydney emphasised the importance of quality control when something is used as a medicine:

Vulnerable patients source cannabis preparations from the black market. These preparations are unregulated with potential for inappropriate cannabinoids for certain indications (eg high THC for pediatric epilepsy), contamination with pesticides or heavy metals, tinctures with no cannabinoids sold as medicine, and poor understanding of appropriate dosing schedules. These safety concerns could be controlled… to help deliver safe and reliable cannabis based medicines to those who would benefit.4

  1. 7.5 To date, only one pharmaceutical-grade cannabis extract (Sativex) has been made available in Victoria, and then only through special importation schemes,5 not through being marketed in Australia. No cannabis products have been lawfully marketed or manufactured in Victoria before. For this reason, it is essential that Victoria takes a cautious approach to ensuring that the cannabis products supplied are of good quality.
  2. 7.6 Likewise, medicinal cannabis supplied in Victoria should be available in forms that are appropriate to the patient’s particular needs. In ensuring this, both the formulation and the cannabinoid content need to be controlled. Quality and consistency are also important to medical practitioners, who would be more likely to approve the use of medicinal cannabis where its quality and consistency could be guaranteed.6

Product control: form and regulation

  1. 7.7 There is no single type of medicinal cannabis. Taking overseas experience as a guide, medicinal cannabis can be supplied as dried cannabis and/or in a range of refined forms. In addition, products can vary greatly in the stringency of regulation applied to them. A description of the products available under any given scheme must identify how the dual variables of form and regulation intersect.
  2. 7.8 As set out in Chapter 2, the products potentially available under a medicinal cannabis scheme can be placed into three groups: pharmaceutical-grade products approved by a regulator like the Therapeutic Goods Administration (TGA), quality-controlled products that have not been conventionally approved, and products that have not been approved or regulated. Examples of each type can be seen around the world:
  • Pharmaceutical grade—The only non-synthetic medicinal cannabis product that has been approved to date is the cannabis extract Sativex, manufactured by GW Pharmaceuticals. No dried cannabis products have been given conventional approval to date.
  • Quality controlled—In Minnesota, for example, a range of non-smokable forms of medicinal cannabis are made available to patients, all of which are subject to quality regulations regarding manufacturing processes and testing. In the Netherlands, on the other hand, various forms of dried cannabis are supplied, and these are also quality controlled through strict rules and testing.
  • Unregulated—In Arizona, medicinal cannabis dispensaries supply patients with various cannabis extracts that are not subject to medical quality controls.7 Likewise, in Hawaii, which currently allows only ‘grow your own’ medicinal cannabis, dried cannabis is not subject to any regulation on quality.8
  1. 7.9 The Commission has sought to identify what combination of form and regulation should be adopted under a Victorian scheme. As explained below, the cannabis products the Commission considers should be provided in Victoria are quality-controlled cannabis extracts. While these products would not be approved as conventional pharmaceuticals, they would be standardised and regulated for quality.

Quality control

  1. 7.10 A system of quality control must specify: the standards to which manufacturers are required to adhere, how the standards are applied in law, and what measures can be used to ensure products have been produced in compliance with the standards.

Objectives of quality control

  1. 7.11 A ‘quality controlled’ product is one which is of a known and consistent composition, both in terms of ingredients and active compounds, and which does not contain dangerous levels of unsafe contaminants.9 A system of quality control for a herbal medicine therefore needs to address three aspects of the product:
  • identity (containing just one plant)
  • purity (freedom from contaminants)
  • content (active constituents within defined limits).10
  1. 7.12 Consistency was a key focus of submissions.11 It was observed that patients should receive a product which is known to be the same in every bottle,12 and ‘legal standardisation’ was called for to ensure products are of ‘consistent quality and efficacy’.13 Cassie Batten and Rhett Wallace told the Commission that they do not know what is in the product they use, and that variation in what they receive (which they can only assess through the appearance and odour of the product) can cause variation in the condition of their son, Cooper.14 Consistency is particularly important because of the botanical, herbal nature of cannabis products. The cannabinoid content of the cannabis plant can vary greatly, depending on the genetic makeup of the plant and an array of growing conditions.15
  2. 7.13 The need for safety of medicinal cannabis products was also emphasised in submissions, with particular calls for pesticides to be banned or controlled.16 Cannabis which has not been regulated for quality, such as ‘street’ cannabis, has been found to have a range of safety issues, such as:
  • unsafe levels of mould and bacteria17
  • unsafe levels of solvent residue in concentrates made using hydrocarbon extraction methods18
  • contaminants, including ground glass19 and fly spray20
  • unsafe levels of toxic pesticides21
  • releasing ammonia when heated (including in a vaporiser)22
  • heavy metal contamination.23

Regulation of herbal medicines in Australia

  1. 7.14 Plant-based medicines are by no means uncommon in modern medical practice. Some common pharmaceuticals, including morphine, paclitaxel and a number of cancer drugs were isolated from and continue to be derived from plant sources.24 Plant-based medicines are also made available for therapeutic use in less refined forms, containing more than just one isolated molecule.25 ‘Herbal’ medicines of this kind are primarily found in the field of complementary medicine.

 

Australian Register of Therapeutic Goods

  1. 7.15 Herbal medicines may be either ‘listed’ or ‘registered’ on the Australian Register of Therapeutic Goods to be sold in Australia, with the vast majority going through the listing route to approval.26 Listed goods are considered to be lower risk than registered goods, and a correspondingly less intense level of scrutiny is applied to applications.27
  2. 7.16 The medicinal cannabis products made available to patients overseas, and currently used illicitly in Australia, are in the nature of herbal medicines. The conventional way for such products to be regulated is through the ‘listing’ process.28 However, products containing cannabis cannot be listed on the Australian Register of Therapeutic Goods.29 This reflects an underlying purpose of the listing process, namely that it is to be used for lower-risk goods, the safety of which is known.

PIC/S Guide to Good Manufacturing Practice for Medicinal Products

  1. 7.17 Whether listed or registered, the manufacture of herbal medicines must comply with the same manufacturing standards as synthetic pharmaceuticals: a set of rules commonly referred to as ‘Good Manufacturing Practice’ (GMP).30 Australia has adopted an international code, the ‘Guide to Good Manufacturing Practice for Medicinal Products,’ developed by the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (jointly known as PIC/S) as the standard to be observed in the manufacture of therapeutic goods.31
  2. 7.18 The PIC/S Guide to Good Manufacturing Practice for Medicinal Products and its annexes are not prescriptive as to what manufacturers must do or how their facilities need to be set up. Rather, they set out a series of aspirational, product-neutral statements to guide industry participants on the sorts of procedures they need to adopt and follow. While the PIC/S Guide frequently states that manufacturers ‘should’ do certain things, in Australia these are treated as compulsory requirements.32
  3. 7.19 The PIC/S Guide has a number of Annexes. Annex 7 relates to the Manufacture of Herbal Medicinal Products. It is based on the following principle:

Because of their often complex and variable nature, and the number and small quantity of defined active ingredients, control of starting materials, storage and processing assume particular importance in the manufacture of herbal medicinal products.33

Other guidelines

  1. 7.20 International guidelines relevant to the production of herbal medicines also exist,34 and various pharmacopoeias include guidance on the production of herbal drugs and extracts.35 Domestically, the TGA has developed the Australian Regulatory Guidelines for Complementary Medicines.36

Creating a framework for medicinal cannabis quality

  1. 7.21 Victoria should seek to make available a regulated source of medicinal cannabis products—notwithstanding that they are not proven, pharmaceutical-grade products—while still providing appropriate protections for vulnerable patients within the scheme. If this structure were to replicate the rigour of the TGA’s assessment process for pharmaceutical-grade products, there would be no point in setting it up. The alternative structure must sensibly be one which does not require the same level of evidence to be supplied, or there would be no expansion of the availability of medicinal cannabis products within a satisfactory timeframe.
  2. 7.22 Equally, it is important that the products authorised under the Victorian medicinal cannabis scheme do not directly compete with or undermine conventional pharmaceuticals. For the reason that they are not as tightly regulated as products approved by the TGA, the products available under the Victorian medicinal cannabis scheme should be different from their pharmaceutical counterparts, including pharmaceuticals derived from cannabis. Patients and doctors would have reasons for preferring pharmaceutical-grade, thoroughly tested cannabinoid products, and as a result the two categories of product would not directly compete.37
  3. 7.23 It is important that, for the separate character of the Victorian products to be preserved, and the pre-eminence of conventional approval to be maintained, the character of the products be distinctive. That is, the government should not endorse these products as replacements for conventional pharmaceuticals. The equivocal evidence base, surveyed in Chapter 2, shows this stance to be unavoidable. Therefore, it is the Commission’s view that medicinal cannabis products should be presented to patients as a form of less-refined, herbal medicine.
  4. 7.24 The Commission considers that the regulation of medicinal cannabis quality should be as follows:
  • Medicinal cannabis products should not be required to be tested for safety or efficacy prior to going to market, and patients should be informed of this fact when being supplied with products.38
  • Medicinal cannabis products should be in the nature of herbal extracts, in that they would contain a range of compounds found in the plant, not isolated cannabinoids.39
  • The concentration of cannabinoids in medicinal cannabis products should be permitted to vary within specified ranges. The uncertainty potentially generated by this would be addressed by requiring products to be tested, and labelled accordingly.
  • Medicinal cannabis products should be subject to manufacturing standards equivalent to those imposed on medicines approved by the TGA.
  1. 7.25 The proposed regulation is less strict than for products approved by the TGA, in that products would not be as rigorously assessed or purified, but they would still be subject to quality control. The government would fail to protect patients if it were to endorse the provision of products without taking steps to ensure their quality. One objective of legalising and regulating medicinal cannabis is to reduce the harms associated with patients accessing cannabis for medical use on the black market, harms which include uncertainty about content, possibility of contamination and an unreliable source of supply.40
  2. 7.26 Some submissions in support of a parallel system for the regulation of the quality of medicinal cannabis supported this type of regulation. Professor David Penington stated he believes medicinal cannabis ‘will end [up] being designated as a regulated “herbal” product’.41 Along the same lines, Laurence Mather, in his submission to the Senate Committee, endorsed the Dutch approach, of standardised herbal cannabis.42
  3. 7.27 It is acknowledged that cannabis is not free of risks, and in many ways is quite distinct from the types of goods ordinarily regulated as herbal medicines. For this reason, the Commission does not suggest that Victoria merely replicate the system of controls for listed complementary medicines. As described below and elsewhere in this report, herbal cannabis products should be subject to the following additional controls:
  • Medicinal cannabis should only be made available to eligible patients, namely those in defined ‘exceptional circumstances’ where there is some evidence cannabis may assist.43
  • Medicinal cannabis should only be supplied to and possessed by someone who has been authorised by a medical practitioner.44
  • Medicinal cannabis products should be batch tested prior to their supply to patients, to quantify content and ensure the absence of contaminants.45

Quality standards

  1. 7.28 For the quality of medicinal cannabis products to be controlled, there is a need to determine the set of standards to which they will be held. Victoria has the option of drawing on internationally accepted standards for agricultural products and drug manufacture, or developing its own set of standards, specific to medicinal cannabis.
  2. 7.29 There are sources on which the Victorian Government could draw to establish the standards with which cultivators and manufacturers must comply:
  • Good Agricultural and Collection Practice
  • Good Manufacturing Practice
  • Codes of practice with specific rules for medicinal cannabis.

 

Good Agricultural and Collection Practice

  1. 7.30 Good Agricultural and Collection Practice (GACP) is a set of procedures that govern the cultivation, harvesting, processing and storage of botanical products used for the production of medicines. Their purpose has been described as follows:

In the case of herbal preparations the production and primary processing of the medicinal plant/herbal substance has a direct influence on the quality of the [active pharmaceutical ingredient]. Due to the inherent complexity of naturally grown medicinal plants/herbal substances and the limited analytical techniques to characterise constituents solely by chemical or biological means, reproducible quality of starting materials of herbal origin requires an adequate quality assurance system for the collection and/or cultivation, harvest and primary processing.46

  1. 7.31 In addition, GACP seeks to ensure that medicinal plants and herbal substances are produced hygienically, reducing microbial contamination to a minimum, and are handled with care, to avoid adversely affecting the herbal substance during its collection, cultivation, processing or storage.47
  2. 7.32 GACP comprises a set of procedures that producers of many types of plant products should follow in order to ensure a safe finished product for consumers. There is, in fact, not one single version of GACP, but a number of guidelines for different industries. The standards most relevant to the production of botanical medicines are those produced by the European Medicines Agency48 and the World Health Organisation.49
  3. 7.33 Producers of medicinal plants in Australia are not directly required by law to comply with GACP. However, manufacturers using herbal ingredients are required to undertake testing and treatment of botanical source materials,50 and must be able to provide specifications for any herbal starting products.51 In this respect, quality control of plant-derived medicines is made the responsibility of the manufacturer. In the case of the alkaloid poppy industry, for example, cultivators licensed by Victoria are not subject to any regulation of their cultivation and harvesting practices from a quality perspective, with quality obligations imposed solely on manufacturers through the licensing and approval processes of the TGA and international pharmaceutical regulators.52
  4. 7.34 Notwithstanding this, in the Commission’s view, cultivators in the Victorian medicinal cannabis scheme should be required to comply with standards of some kind. UTT BioPharmaceuticals agreed with this, recommending that the system regulate the finished product, the botanical ingredients it contains, and the cultivation process.53 While this would depart from the approach adopted through the listing/registration processes in the Therapeutic Goods Act 1989 (Cth), the Commission considers that the novelty of cannabis demands a cautious, transparent approach.
  5. 7.35 It should be noted that Victorian and Commonwealth legislation that restricts the activities of all agricultural producers would also apply to cannabis cultivators.54

 

Recommendation

  1. 31 Licensed cultivators should be required to comply with appropriate Good Agricultural and Collection Practice.

 

Good Manufacturing Practice

  1. 7.36 In the Commission’s view, manufacturers in the Victorian medicinal cannabis scheme should be required to comply with the PIC/S Guide to Good Manufacturing Practice for Medicinal Products.55 Several submissions called for these standards to be applied.56 As explained above, because they are worded in general terms, Good Manufacturing Practice (GMP) can be applied to the manufacturers of botanical products just as they can to manufacturers of synthetic compounds. Relevant international guidelines57 could also be supplied to guide manufacturers.

Recommendation

  1. 32 Licensed manufacturers should be required to comply with Good Manufacturing Practice, as reflected in the PIC/S Guide to Good Manufacturing Practice for Medicinal Products.

 

Cannabis-specific codes of practice

  1. 7.37 In connection with the licensing of manufacturers, the TGA has detailed protocols and a body of inspectors and officials with specialised knowledge about the practical requirements of GMP. This expertise does not presently exist in the Department of Health and Human Services because the Department does not have responsibility for the regulation of drug/herbal product manufacturers or the enforcement of GMP.58 In addition, the Department would need to determine how to apply the general standards of GMP to cannabis production—for example, the standards refer to acceptable limits of pesticides and microbes, but there is no specification of precisely what that level would be.59 In summary, the supervision exercised by the TGA over manufacturers cannot be replicated in the Victorian scheme merely through the application of the PIC/S Guide.
  2. 7.38 To address these possible practical difficulties, the Department could prepare new rules, specifically for application to cannabis production.60 This would provide certainty to businesses seeking to participate in the scheme, and to government inspectors in determining whether licensees are compliant. The new rules could be used in substitution for or in addition to GACP or GMP. If operating alongside them, the rules could function to explain how GACP/GMP are considered to apply in the context of cannabis production. This approach is adopted in the Netherlands.61 Cannabis-specific production guidelines have also been adopted in, among other places, Canada,62 Colorado and Minnesota.63

Enforcing the standards

  1. 7.39 There are a number of tools through which the Victorian Government could apply quality standards to manufacturers (from least to most restrictive):
  • allow the industry (licensed cultivators and manufacturers) to self-regulate, and for optional accreditation schemes to give consumers information about the standards applied
  • arrange for manufacturers to make cannabis products under contract to the Victorian Government, and make production standards terms of the contract
  • make compliance with manufacturing standards a condition of the licences held by cultivators and/or manufacturers
  • set out rules in legislation.
  1. 7.40 Self-regulation would not be appropriate, as patient safety should be paramount under the scheme. Conversely, setting out specific rules in legislation would be too restrictive, preventing the government from updating procedures and standards as the industry develops. Applying standards to licensed manufacturers through contractual terms would not be sufficiently transparent to give patients and medical practitioners confidence in the scheme, and would deprive inspectors of necessary enforcement powers.
  2. 7.41 In the Commission’s view, the GMP standards referred to above and any local guidelines developed for cannabis should be applied to manufacturers and cultivators through incorporation of the relevant standards in regulations64 and through licence conditions.
  3. 7.42 Standards could be practically enforced through a combination of the following mechanisms:
  • inspections at the time of application to ensure facilities and operators are set up to comply with GACP/GMP65
  • requiring licensees to prepare and submit production plans66
  • regular inspections throughout the period of the licence to ensure ongoing compliance67
  • record-keeping and reporting obligations imposed on licensees68
  • audits conducted by third parties69
  • infringement notices, improvement notices70 and licence variation available where noncompliance is observed.

Efficacy testing

  1. 7.43 The approval process undertaken by the TGA evaluates products for ‘safety, quality and efficacy’.71 Sponsors seeking to register a therapeutic good must present to the TGA evidence that the good is efficacious for the requested indication.72 The less rigorous listing process does not evaluate efficacy, but requires manufacturers to possess evidence supporting any therapeutic claims they wish to make.73
  2. 7.44 This raises the question of whether products should be permitted to be sold under the scheme if they have not been specifically tested in humans for effect. One submission stated that it would be ‘unfair’ to apply the efficacy criteria for registered medicines to medicinal cannabis products and argued that departure from ordinary standards is justified where ‘medical science and regulatory processes are failing to meet the needs of society’.74 However, a number of other submissions advocated for clinical trials, on the basis that the efficacy of cannabis was not yet adequately established.75
  3. 7.45 In the Commission’s view, the scheme should operate on the basis that the efficacy of Victorian medicinal cannabis products has not been established. The Victorian scheme should ensure a product is free of unsafe components and its composition is sufficiently known. However, it would not be feasible or desirable for the scheme to make approval of a particular medicinal cannabis product contingent on proof (whether to conventional standards or otherwise) that the product is effective to treat a given indication. Clinical trials are costly and time-consuming to run, and placing similar barriers to product approval as already exist under the TGA would not facilitate access to medicinal cannabis in any meaningful way.
  4. 7.46 Because their efficacy has not been specifically proven, products offered under the medicinal cannabis scheme would be clinically less useful than those approved through conventional channels. While this would provide patients and their treating medical practitioners with fewer assurances than approval by the TGA, this is a tolerable outcome because the scheme would complement, not supplant, the approval processes of the TGA, to allow access to less-proven substances in exceptional circumstances.
  5. 7.47 There is a risk that products would be offered to patients despite having no therapeutic value, or with their therapeutic value overstated.76 However, as the government would be the sole distributor, there is no risk of a third-party manufacturer making inaccurate efficacy claims.
  6. 7.48 It is important for patients to be clearly informed when deciding to take medicinal cannabis dispensed under the Victorian scheme that the products have not been subjected to the conventionally rigorous tests of efficacy imposed by the TGA, and that other conventional products exist which have that status. By opting for the ‘alternative’ of medicinal cannabis, the patient must be informed that that the product may not be effective for them. There is a risk that attaching the imprimatur of the state to these regulated products would lead consumers to assume that they have been clinically tested for efficacy. The advice given to patients by doctors and the government in authorising them to use cannabis would therefore be fundamental to ensuring that patients’ consent to use such products is informed.77

Clinical testing of side effects

  1. 7.49 For a therapeutic good to be included on the Australian Register of Therapeutic Goods, its safety must be known. In the case of listed goods, safety is ensured by requiring that the product only contain ingredients already known to be safe. In the case of registered medicines, considered to be higher risk, the sponsor must present evidence regarding the product’s safety. That is, the medicine must have been tested for side effects prior to obtaining approval.
  2. 7.50 The risks and side effects of cannabis are relatively few and minor.78 In addition, they are reasonably well documented, although mostly not in a clinical setting, and in this sense cannabis is not comparable to a drug containing a new molecule. Where a new complementary medicine is sought to be used, its safety can be established by documenting historical evidence of its use.79 Cannabis has been extensively used and studied, and while it is by no means completely safe or free of side effects, the Commission considers that quantifying cannabinoid content and disseminating educational materials about known attributes and side effects of medicinal cannabis to medical practitioners would be sufficient to allow the patient and their treating doctor to identify risks for the patient, and render safety testing of individual products unnecessary.

Product approval

  1. 7.51 Any Victorian medicinal cannabis scheme should only provide medicinal cannabis products that have been approved by the government. A list of approved products would be publicly available, and new products could be added by the Secretary of the Department of Health and Human Services. A submission made on behalf of the cannabis community of Victoria opposed a scheme in which the available products are limited by the government in this way, stating that it would not satisfy patient needs.80 The Commission considers, however, that this regulatory mechanism is essential to give clarity to law enforcement, to satisfy doctors about products’ reliability and to maintain government control over the available products.
  2. 7.52 By requiring that medicinal cannabis products be approved, the scheme could draw a clear line between products that are lawful and those that are not. Amendments to the Drugs, Poisons and Controlled Substances Act 1981 (Vic) would authorise medicinal cannabis patients to possess only the approved product specified in the Authority to Dispense. Nominated carers would be similarly authorised.81
  3. 7.53 Medical practitioners issuing an Authority to Dispense would specify the product to be dispensed, in a similar way to prescriptions for conventional medicines. To this end, the Department of Health and Human Services should make available to medical practitioners a list of approved products and their properties.
  4. 7.54 A product approval should specify at least the following matters:
  • its THC content, as a percentage
  • its CBD content, as a percentage
  • its formulation (for example: extraction, tincture, oil)
  • permitted ingredients
  • the brand name under which it will be sold
  • the contents of its label.
  1. 7.55 Upon taking possession of cannabis products from manufacturers, the government should ensure that the product corresponds with its approval. In particular, through testing (detailed below), it should ensure that the cannabinoid content of the product is consistent with the approval, within a specified tolerance range.82
  2. 7.56 Unlike the process for including new products on the Australian Register of Therapeutic Goods, obtaining approval of a medicinal cannabis product should not be initiated by the proposed manufacturer, nor require the manufacturer to test the product in clinical trials before approval is granted. This is because the design of the scheme is such that the government orders specific quantities of designated cannabis products, which are then delivered to it by the licensed manufacturers. That is, the government controls the levels of supply and, correspondingly, should control the range of products that are made available.83 However, the process for obtaining new products would involve consultation between the manufacturer and the Department, as the introduction of a new product would depend on the ability of the manufacturer(s) to produce it safely and consistently.
  3. 7.57 The Secretary’s discretion to approve new products should be unfettered. In practice, the Secretary would be likely to take into account scientific developments regarding the utility of different types of cannabis for eligible conditions, patient demand for new products, patient safety, and pharmacological considerations regarding rate, intensity and duration of absorption.
  4. 7.58 A process should be established by which products would be considered for approval. This should include consultation with the medical profession and the Expert Advisory Committee on Medicinal Cannabis or a successor advisory body.84 The Department would issue guidelines regarding the product development and testing which would need to take place before the product is approved—for example, a manufacturer may be asked to demonstrate their ability to control cannabinoid concentration before a particular product is approved.

Recommendations

  1. 33 The Secretary of the Department of Health and Human Services should have the power to determine which medicinal cannabis products may be manufactured under licence and dispensed in Victoria.
  2. 34 The Secretary of the Department of Health and Human Services should establish and publish a register of medicinal cannabis products approved for sale in Victoria. The register should specify, for each product:
  3. (a) its THC and CBD content, as a percentage
  4. (b) its formulation
  5. (c) permitted ingredients
  6. (d) the brand name under which it will be sold
  7. (e) label contents.

 

 

Batch testing

  1. 7.59 Medicinal cannabis products would be tested for two reasons:
  • to ensure the quality of products (namely, to ensure that the actual quantity of cannabinoids in the product matches the concentration listed on the product approval)
  • to ensure the safety of products (namely, to ensure that the product does not contain unsafe concentrations of contaminants, such as moulds, microbes, harmful or prohibited pesticides, solvent residue and so on).
  1. 7.60 Consistently with the requirements of the TGA, testing should be conducted to ensure that any ‘quantitative claim’ made (that is, any claim made regarding the THC or CBD content of a product) is verified, and this testing should take place on every batch produced.85 Testing should be performed on the finished product (the oil, tincture or other product), not on the raw plant matter.86 The specified cannabinoid content on the approval would need to be within a prescribed tolerance, and failure to do so would enable the Secretary to reject the batch.87
  2. 7.61 Testing could either be performed by the manufacturer or by a third party. For transparency reasons, the Commission considers that testing by a third party would be preferable.88 If internal testing is to be used, no additional legislative change would be required. If third parties are to be used for testing, the legislation would need to authorise certain facilities to possess medicinal cannabis for the purpose of testing. It is suggested that the provisions authorising certain facilities to undertake testing could be based on current provisions empowering the Chief Commissioner of Police to declare testing facilities to undertake forensic testing of drugs.89
  3. 7.62 In determining whether to authorise a particular facility, the Secretary would have regard to whether it would use appropriate technologies to give an accurate indication of product strength.90 The technology used would need to be adapted to the purpose of the testing. While some testing technologies have as their purpose determining which compounds are present in a sample, others are intended to quantify the amount of particular compounds present in a sample. A facility would need to be properly equipped to test the potency91 of cannabis, and to test for an appropriate range of pesticides, solvents, heavy metals and microbial contaminants.

Recommendation

  1. 35 The Secretary of the Department of Health and Human Services should have the power to authorise independent testing facilities in Victoria to test medicinal cannabis products.

 

Recommendation

  1. 36 All medicinal cannabis products manufactured under a Victorian scheme should be subject to testing by an authorised testing facility to confirm whether the cannabinoid content correlates with that specified on the label and to identify the presence of any contaminants.

 

Labelling

  1. 7.63 Submissions highlighted the value of labelling as a means of conveying information about the product to patients.92 Matthew Pallett submitted that ‘[a]ll commercial cannabis products should carry labelling stating percentage of active constituents so consumers can make an informed decision about the type of cannabis they wish to consume’.93
  2. 7.64 As noted above, the scheme should allow for cannabinoid content to vary slightly from the specified content on the approval. Therefore, medicinal cannabis products should be labelled with the precise cannabinoid content of the product. Labels could also convey warnings regarding the risk of driving,94 the untested nature of the product, penalties attached to diversion and so on.

Post-market surveillance

  1. 7.65 Even cannabis products that have been subject to quality control regulations could later be found to be unsafe. For this reason, the regulation of therapeutic goods always includes a system to monitor products after they go onto the market. This allows the regulator both to monitor rare or long-term adverse effects, and to undertake recalls and investigations if unexpected contamination is detected.
  2. 7.66 The TGA has a system for reporting adverse events. Reports are primarily made by patients, manufacturers, medical practitioners and pharmacists. The information received is logged, and may lead to further evaluation. Should a safety concern be identified, the TGA can take actions including information bulletins, labelling changes, withdrawing or limiting a product’s registration, or requesting that further studies be undertaken.95 An analogous system should be adopted in any medicinal cannabis scheme.96

Forms of medicinal cannabis

  1. 7.67 Submissions frequently argued for the scheme to make available a range of medicinal cannabis products, to allow for the varying preferences and medical needs of patients.97 In addition to a variety of strains, the scheme should allow for a variety of delivery modes. This is important as different patients and conditions are asserted to respond better to different products.
  2. 7.68 A considerable amount of knowledge exists, both in industry overseas and in the Australian illicit market, regarding the composition of cannabis, the ways it can be refined and how products can be adapted to suit the needs of patients. The Commission heard from many people who had become expert on the topic of medicinal cannabis, both through reviewing the literature and cultivation experience.98
  3. 7.69 However, there is also a good deal to learn, and many assertions that are frequently made regarding cultivation practices, extraction methods and pharmacology do not appear to be based on science—indeed, this is not surprising given that there are few legal means for this information to be tested and improved.

Smoking should be avoided

  1. 7.70 Historically, cannabis has been commonly administered by smoking.99 As discussed in the Issues Paper,100 smoking has a number of adverse health consequences and is an unreliable way of dosing. Many of the side effects associated with smoking cannabis are not observed for other modes of administration.101 There is also the possibility of accidental ingestion by third parties through passive smoking.102 A number of submissions urged that smoking be discouraged or prevented under the proposed scheme, or remarked upon the harmful health effects of this mode of administration.103 However, as noted by Cancer Action Victoria, the risks associated with smoking are of less importance for a person with a terminal illness.104
  2. 7.71 In addition, over the past three decades governments have passed increasingly restrictive laws aimed at protecting public health by prohibiting or discouraging smoking,105 while the not-for-profit sector has run extensive public health campaigns to the same end. A scheme which made cannabis available and enabled or encouraged smoking as a delivery method would be inconsistent with the outcomes and messages that successive governments have worked hard to achieve in this area.
  3. 7.72 There are two distinct means by which a medicinal cannabis scheme could seek to avoid the smoking of cannabis:
  • by allowing dried cannabis (in addition to other forms) but prohibiting or discouraging patients from consuming it by smoking
  • by only allowing forms of cannabis that cannot be smoked.

Allowing dried cannabis but discouraging smoking

  1. 7.73 It would be possible to establish a scheme which provided dried cannabis but did not promote smoking. The Victorian Government could provide advice to patients and health professionals regarding other forms of delivery, such as vaporisation and ingestion through food or tea. Pharmacists could supply informational material and be able to sell vaporisers, which heat cannabis without combusting it, avoiding many of the negative health effects observed with smoking. Alternatively, legislation could be enacted which seeks to prevent or limit smoking of cannabis by users who have obtained it for medicinal use.
  2. 7.74 In the Netherlands, patients can only purchase dried cannabis, in the form of whole dried flowers or flowers which have been ‘granulated’. Government information programs encourage consumption by vaporisation, in a tea or in edible/baked goods.106 However, in practice a large number of patients administer their medicinal cannabis by smoking it—up to 80 per cent of patients are estimated to do so.107
  3. 7.75 Several submissions called for dried plant matter to be among the forms of cannabis available under the scheme.108 One expressed the view that, if dried cannabis were made available, few patients would smoke it in any event.109
  4. 7.76 Cancer Council Victoria stated that it ‘would not support a scheme where the smoking of cannabis is the predominant delivery method for patients.’ It encouraged the consideration of models ‘where alternative delivery methods, such as the use of oils and vaporisers, are the primary approach’.110
  5. 7.77 Victoria Police opposed the provision of dried plant cannabis to patients, commenting that ‘[i]t would not be forensically possible to differentiate crude cannabis grown illicitly from crude cannabis grown for medicinal purposes.’111 Appropriately labelled, non-smokable cannabis would be more easily differentiated from illicit cannabis by law enforcement authorities.
  6. 7.78 While there are a range of educational measures and offence provisions the government could adopt to discourage users from smoking the dried plant form of cannabis, and there are ways of administering the dried plant form which do not involve smoking, the inevitable reality is that if dried cannabis is available, some patients will probably smoke it. A law which purported to prohibit the act of smoking medicinal cannabis, including on private property, would not be enforceable. If Victoria wishes to prevent medicinal cannabis supplied under the scheme from being smoked, an alternative approach will be required.

Allowing only non-smokable forms

  1. 7.79 The Victorian Government could elect to only make available forms of medicinal cannabis that cannot be smoked. Non-smokable forms could include extracts such as oils and concentrates, which can be swallowed or vaporised, pills, capsules and tinctures.112
  2. 7.80 There are many challenges involved in allowing only non-smokable forms of medicinal cannabis to be sold. Requiring producers to refine cannabis before it is sold would increase the cost of the product to the government113 and the cost of administering the regulatory system. Non-smokable extracts of cannabis can be highly potent, much more so than dried cannabis, making the risk of unwanted psychoactive effects much higher (this risk is heightened with oral forms, due to the slow rate of onset).114 Finally, because patients have less control over the way the cannabis is prepared and administered, prohibiting smokable forms may reduce levels of engagement with the system and promote continued reliance on the black market.
  3. 7.81 A further drawback to allowing only non-smokable forms of cannabis to be sold is that patients would be deprived of safe administration methods which have a low production cost. Research and knowledge is growing about the use of vaporisers (devices which use heat to release cannabinoids and other volatile compounds) to administer dried cannabis.115 Research indicates that this method allows patients to obtain the benefits of inhalation (fast uptake and short duration of effect) while avoiding many of the harms associated with smoking (bronchial irritation, potential carcinogenesis and the effects of second-hand smoke on other people).116
  4. 7.82 In addition, licit non-smokable cannabis products are very new, making the task of regulating them difficult and uncertain. Information on the safety and efficacy of cannabis is limited, but the information that does exist mostly pertains to dried cannabis. As a result, the introduction of a scheme involving only non-smokable forms is to some degree a foray into the unknown—indeed, to the Commission’s knowledge, only two jurisdictions (Minnesota and New York) have introduced medicinal cannabis schemes that do not allow the dried plant form, and only one scheme has so far commenced. A number of states in the United States, however, do allow non-smokable forms of cannabis to be sold alongside dried plant cannabis, with highly variable regulations imposed. In addition, non-smokable forms are harder to regulate and the system for licensing manufacturers outlined above would be largely unnecessary if oils and other extracts were not provided under the scheme.
  5. 7.83 Nonetheless, the Commission is persuaded that a scheme which allows smoking should be avoided, and accepts that the only feasible way of ensuring this is through providing only non-smokable forms of medicinal cannabis. This approach would also have the advantage of enabling more accurate purity control and dosing.

Formulations and delivery systems

  1. 7.84 A Victorian medicinal cannabis scheme should enable production of a variety of formulations and delivery systems. Different patients have different needs and preferences in relation to medicinal cannabis – for example, children will generally require a product taken by mouth, for ease of administration, while people affected by nausea and vomiting may not want a product they need to swallow.117
  2. 7.85 Submissions called for the scheme to make available cannabis in the following extracted forms:
  1. 7.86 Many overseas jurisdictions allow the sale of ‘edibles’—foods such as chocolate and cookies that contain an extract of cannabis—through their medicinal cannabis schemes. A number of concerns were raised in submissions regarding such products. One submission argued that edible products should be strictly controlled on the basis that they can cause bad publicity for a medicinal cannabis scheme.126 Others observed that edible products present a risk to children127 and to patients, who are less aware of the dose they are receiving.128 The Commission agrees and does not recommend that they be included at the outset of the scheme.
  2. 7.87 If dried cannabis is not supplied under the scheme, this precludes patients from ‘vapourising’ cannabis, as explained above. The Commission heard anecdotal reports that inhalation is a better mode of delivery for people using cannabis to treat pain129 and that its onset is quicker.130 So that the inhalation route can be among those available for some categories of patient, the Secretary of the Department of Health and Human Services should evaluate the advantages and disadvantages of vaporisable concentrates, like those used in e-cigarettes, as a means of delivery of medicinal cannabis.131
  3. 7.88 The government should ensure, through the licensee selection process and selecting products for approval, that the range of available products spans a range of administration routes and pharmacological properties.

Strains

  1. 7.89 The cannabis plant comes in an extensive number of strains.132 These strains, which represent particular subtypes of cannabis, can be differentiated using a number of characteristics, including the dominant species (sativa or indica), the cannabinoid content (THC, CBD and others) and the terpene profile.
  2. 7.90 In some overseas jurisdictions, medicinal cannabis producers market many ranges of strains to patients, under colourful and distinctive strain names not dissimilar to the branding for alcohol and food.133
  3. 7.91 A submission made on behalf of the cannabis community of Victoria asserted that it:

does not support the idea of limiting forms of medicinal cannabis under the operation of a proposed medicinal cannabis scheme for Victoria. This submission has promoted the unique applications and circumstances in which various forms of cannabinoid medicines serve particular patient ailments and needs. A patient’s ability to access cannabis medicine is a key requirement of any proposed scheme. That implies that the medicine must be appropriate and in the form appropriate for the patient.134

  1. 7.92 Professor Laurence Mather has also drawn attention to the complex nature of cannabis products:

It is well known that medicinal preparations made from the cannabis plant typically contain several hundreds of known chemical substances, and many of these demonstrate activity in relevant pharmacological models. Moreover, these substances occur in varying concentrations in different strains of cannabis plants, with additional variations introduced by conditions of plant growing, harvesting, storage and processing. Thus ‘cannabis’ cannot be regarded as a particular drug and therein lies an issue for regulatory bodies and for intellectual property acquisition by pharmaceutical companies.135

  1. 7.93 Medicinal cannabis users often differentiate between strains of cannabis based on the type of cannabis from which they are derived (‘sativa dominant’, ‘indica dominant’ or ‘hybrid’). The species is perceived to affect the nature of the psychoactive effects which the user experiences. The indica strain is considered, for example, to provide pain relief without the ‘high’. However, the reason for the perceived differences between sativa and indica varieties of cannabis is as yet inadequately understood, and complicated to assess due to the number of potential compounds involved. Cannabinoid and terpene content can vary as much within each category as between them.136 Increasingly, in the United States the distinctions between different strains are complicated by commercial competition in the marketplace.
  2. 7.94 Notwithstanding this, producers respond to and influence consumer demand by providing a number of strains in all three categories, even where extracts are supplied, allowing patients to try a range of strains to determine which best addresses their symptoms. At the start of its medicinal cannabis scheme, the Netherlands Office of Medicinal Cannabis made available only sativa strains of cannabis; later, in response to patient demand, it introduced an indica strain (marketed as ‘Bedica’).137
  3. 7.95 The Commission agrees that the approval system put in place should allow for producers to cultivate and market a range of strains. There are many compounds in the cannabis plant, and the quantities of each vary from strain to strain. However, while the level of strain variation seen in countries such as Canada and the United States caters well to patient demand, in that it caters to a range of preferences and allows them to look for a strain that ‘works well for them’,138 it is difficult to incorporate this level of variation under the distribution model required by the Single Convention on Narcotic Drugs 1961. That is, where the government is the sole purchaser of cannabis products, there is no interface between the patient and the manufacturer, limiting the extent to which the patient can communicate with them about their needs.139 The Victorian Government will need to specify, in issuing manufacturing licences, which products it wishes to procure. Further, were an unlimited number of strains provided, doctors would be incapable of selecting the strain that is most therapeutically appropriate for patients - this could only be determined through a process where the patient had the freedom to select their own product. Therefore the Commission considers that only a modest number of strains should be made available under the Victorian scheme, described by neutral terminology.140

Cannabinoid content

  1. 7.96 Cannabis is known to contain between 80 and 100 cannabinoids. The medicinal effects of these are only slowly coming to be understood, with some hypothesising that the effect of certain cannabinoids is greater in combination than in isolation (referred to as the ‘entourage effect’).141 It will be some time before the precise mechanism is known for many of the apparent benefits observed by patients using the plant form of cannabis or cannabis extracts.
  2. 7.97 Nonetheless, it is apparent that variation in cannabinoid levels between different cannabis products results in differing patient outcomes. The Victorian scheme should therefore allow for cannabis products to be supplied that vary in cannabinoid content. Under the Minnesota medical cannabis scheme, by way of example, manufacturers supply products with three or four different THC/CBD concentrations.142 Similarly, in the Netherlands, Bedrocan supplies five strains of cannabis, each with a specified level of THC and CBD.143 The Commission notes that the submission on behalf of the cannabis community of Victoria opposed this model, stating that ‘[c]annabis medicine cannot be approached in this way. It must be specifically tailored for and to, a patient’s individualized needs’.144
  3. 7.98 Some people called for products high in CBD and low in THC to be made available on the basis of their efficacy for certain conditions such as epilepsy.145 It was noted in several submissions too that products with very little THC would have a minimal or non-existent psychoactive effect, and would therefore be of limited interest for recreational users.146 The Commission agrees with this perspective. In addition, the lack of psychoactive effects means high-CBD products would have a better safety profile than high-THC products.147 As a result, the government may consider approving products high in CBD more readily than those with a high level of THC.
  4. 7.99 Others called for products containing a balanced ratio of THC and CBD to be made available.148 Professor David Penington submitted that Victoria should develop a product with equivalent levels of THC and CBD, drawing on evidence showing that CBD ‘counteracts the negative effects of the potent and psychotogenic THC on the brain’, reducing or eliminating its tendency to induce psychosis.149 Others also drew attention to the antipsychotic and neuroprotective properties of CBD.150
  5. 7.100 Some submissions argued for products containing high levels of tetrahydrocannabinolic acid (THCA) to be made available under a Victorian scheme.151 THCA is the precursor chemical to THC, and is not believed to be psychoactive152 nor to be metabolised to THC in the body.153 The cannabis plant contains predominantly THCA, which is progressively converted to THC through the drying process, and can be converted further by heating. It has been asserted that THCA is an effective treatment for the symptoms of epilepsy,154 diabetes155 and autism.156 However, the research on THCA, as distinct from THC, is at an early stage. Studies have been carried out on animals157 and in cultures,158 but rigorous human studies of the isolated cannabinoid are yet to be conducted.159 Although the accounts provided to the Commission regarding results achieved with THCA tinctures have been strongly expressed,160 the lack of research on this compound means that the Commission cannot recommend that THCA extracts be made available outside trials at this stage.
  6. 7.101 The Commission considers that the Victorian medicinal cannabis scheme should be able to provide cannabis products with varying quantities of the two best-understood cannabinoids: THC and CBD.161 At this stage, there is insufficient evidence to warrant the provision of products that are differentiated by other cannabinoids, and medical practitioners would lack the ability to select an appropriate product. As science develops and production methods improve, the Secretary of the Department of Health and Human Services may decide to approve further products.
  7. 7.102 The Secretary could ensure that a variety of cannabinoid compositions are available under the scheme through the competitive selection of licensees. The Secretary could also build incentives into the contract for the development of products, and allow licensees to cultivate cannabis for experimental purposes separately to their medical allowance. A mechanism for obtaining expert advice should also be incorporated.
  8. 7.103 It would also be possible for rules to be made in legislation or regulations, stipulating the maximum concentration of THC, the minimum concentration of CBD or the minimum THC:CBD ratio that Victorian medicinal cannabis products would be permitted to contain. This would enable the Secretary to ensure that highly potent forms of cannabis are not available,162 and that protective levels of CBD are included. However, the Commission does not consider that the government should adopt this approach. As stated elsewhere, there is little scientific research on the ‘safe’ levels of THC and CBD, so it would not be possible at this point to set outer limits of this kind. As research develops, the government should be in a position to respond flexibly, and regulated concentration limits would present an obstacle to this. The Secretary could address safety concerns by maintaining control over the products approved.

Whole-plant medicines versus isolated cannabinoids

  1. 7.104 Several submissions called for only ‘whole plant’ or ‘natural’ cannabis to be provided, and for ‘pharmaceutical’ cannabis, or forms of cannabis which isolate one cannabinoid or a few cannabinoids to be avoided.163 Others submitted that cannabinoids need to be extracted and studied in order for cannabis to be studied.164
  2. 7.105 While not containing raw plant material, nonsmokable products made available under a Victorian medicinal cannabis scheme would be in the nature of ‘whole plant extracts’, in that they would contain a range of cannabinoids and other substances, not isolated or synthetic cannabinoids. At the same time, though, they would be subject to strict controls regarding cultivation and manufacture, as set out above. This is consistent with their regulation as a herbal product.165

Recommendation

  1. 37 Medicinal cannabis products supplied under any Victorian scheme should:
  2. (a) not include products that can be smoked
  3. (b) include a variety of delivery systems, such as tinctures, oils, capsules, sprays and vaporisable liquids
  4. (c) provide for variation in cannabinoid content
  5. (d) be kept under review in view of developments in technology and medical knowledge about the medicinal use of cannabis and specific cannabinoids.

 

 


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