[Medicinal Cannabis Scheme Health Professionals Session]

So first of all, I'm just saying that if you're here to learn more about the details of the government's proposed referendum on the legalization of recreational cannabis, you might have to wait a bit longer. So the focus of this session is on medicinal cannabis, and medicinal cannabis, which is available only on prescription. New Zealanders will choose whether or not to legalize recreational cannabis as part of a referendum at the 2020 general election.

So I'd like to introduce Chris James, who's the group manager of Medsafe. Medsafe is New Zealand Medicines and Medical Devices Safety Authority, which is the business unit within the ministry responsible for the regulation of therapeutic products in New Zealand. Chris.

As Andrea mentioned, I'm the group manager of Medsafe, medicines and medical device regulator. Medsafe also regulates psychoactive substances. And we're leading the implementation of a medicinal cannabis scheme.

Just a bit of background-- from my perspective, I've been at Medsafe around 12 years, both in pre-market pharm chem assessment, and then into clinical and pharmacovigilance and risk management, and then into management roles. Before that, I was a pediatric and neonatal pharmacist for 10 years, in New Zealand and the UK. Just a bit of background for you.

I know this is a health professional session. And I imagine those in the audience will have had some experience with either medicinal cannabis products, or people asking questions about medicinal cannabis products, and patients seeking information. So what we want to do is really provide you with some information about what is proposed here, and really get your feedback on what you need, obviously what you think of the proposals, and what you need as well, in terms of information, to help you with those discussions with patients.

So a bit of background to the scheme, so you know why we're here. The key objective that the new government came in with was to improve access to affordable, quality medicinal cannabis products. And to do this-- they see it as a priority in what they call the 100-day plan. And that was to introduce legislation that did a number of things. So the first one was to provide a statutory defeat for terminally ill people to possess and use illicit cannabis, on compassionate grounds, and in principle, to introduce a medicinal cannabis scheme that would provide an ability to cultivate, manufacture, and supply medicinal cannabis products to a quality standard.

The legislation was also put in place to de-schedule CBD, cannabidiol. So cannabidiol came out of the Misuse of Drugs Act. But one of the key things about that is it's still scheduled in the Medicines Act. And this is where we've had a little bit of confusion because of the two bits of legislation that we have in New Zealand. So CBD, while it's not controlled, is a controlled drug. It is still a prescription medicine.

So this legislation entered parliament and was passed at the end of last year, in December. And it's allowed for people requiring palliation to be eligible for statutory defense; allowed for regulations to be made to describe standards for all stages in the cultivation and manufacture for these products; it also allows the license holder, under the scheme, to use locally-sourced plant, fruit, and seeds; and also required that the regulations to actually make this live, make this come into force, should be passed within 12 months.

And so that's basically the 18th of December, which, for those who had experience in government, is extremely fast. For those who have had some knowledge about what's happened overseas, that's about two to three times faster than any other country has put this in place.

Because of that, that's why we have been in contact with all of our regulatory colleagues. Because it tends to be the medicines regulator that is an offshoot of the medicines regulator that is implementing throughout the world. And so we've been able to use our contacts to learn about what went well, and what didn't go well, and what they would do if they had the chance to plan it and do it again. So that's been quite helpful.

A little bit of international context on this, which really steers us and as far as what we need to put in place. And there are a number of conventions and international conventions that New Zealand has signed up to that look to restrict production, export, import, manufacture, et cetera of narcotic drugs, including cannabis, to be exclusively for medical and scientific purposes.

The key one is the Single Convention on Narcotic Drugs, 1961. That establishes a framework for control of narcotics to facilitate the availability of these products as medicines or for medical purposes. So under that convention, New Zealand has to carefully control the cultivation and manufacture, and also has to set up what's called an agency to do that and to regulate cannabis-based products. So by the term, I mean, agency-- what we tend to say is agency with a little a, not a big A. You don't have to have another department, and an office in Wellington of 20 people just looking at medicinal cannabis, it just means that you need to have a regulator in place, which could be part of Medsafe and within the Ministry of Health, to do that.

The New Zealand context around this is we have the Misuse of Drugs Act, 1975. So it's not overly new, but it serves a purpose for what we're trying to achieve here. We already have laws that allow the import, export, and manufacture of medicinal cannabis. These laws do not allow lawful cultivation of cannabis plants for medicinal purposes, for commercial purposes. What they do allow is we can license for scientific and medical research. And that is happening now.

We are proposing to control the supply of medicinal cannabis products through our licensing regime, and that's effectively allowing cultivation manufacture and supply commercially, so products can be developed and then essentially accessed to patients. And the proposal is that this access to a patient is through a prescription. And then a prescription is then presented, as with any medicine, to a pharmacy. And then a pharmacy dispenses that medicine. So obviously these are all things that we're interested in feedback on.

The agency, as I've mentioned, is to be established within the Ministry of Health. We already administer aspects of the Misuse of Drugs Act. We already license, for a number of controlled drugs, for therapeutic purposes. We also regulate, for example, industrial hemp, cultivation of low-grade THC hemps for food. We do that with MPI. And as I mentioned, we are already currently issuing licenses for medical and scientific research.

So with this in mind, improving access to products-- there's two sides to this. The first is increasing supply of products. There are, as you would have seen, a few products. There is one approved medicine-- it's called Sativex, which is approved for spasticity in MS. And obviously there are a couple of unapproved products which are in circulation as well. Tilray is one, for instance, that we commonly see. The legislation change here, and what we're putting in place, is looking to increase the supply of products that meet a quality standard. And that would allow-- so we're allowing commercial cultivation of cannabis in New Zealand, manufacture of products in New Zealand, and also local and imported products, as long as they meet the quality standards.

The other side to this is about improving access to patients. And this is around products may be more available, but what reassurance do health care professionals have about the products, about what's in them, about the consistency, about how they dose titrate, how they manage interactions, how they manage adverse reactions. And that's where a key part of this is how we provide information, both with the actual products, because these products are unlikely to have full data sheets like medicines have now, with randomized controlled trials to phase III level, with thousands of patients.

We are expecting to have information about products, such as formulation and clinical data that they do have available. But then we're also looking at what information do we need to provide to health care professionals generally about medicinal cannabis products as new evidence and new clinical studies come through, including, for instance, a lot of research happening in pharmacokinetics. What are we seeing in terms of inhibition of PGP and hepatic enzymes. What does that mean for interactions? And so we need to provide that information for health care professionals so you can make decisions and have conversations with patients.

So that's it for me for now. I'll hand over to Andrea about quality standards of manufacture, and then we'll cover off prescribing.

OK, thanks, Chris. I'm going to talk now about quality standards, and cover off a wee bit about the manufacture. Because they manufacture quality standard is a key part of the quality assurance of a product. And then I'm going to talk a wee bit about the product quality standards in the finished dose forms that we are proposing to be allowed under the scheme.

So why are quality standards important? I think you'll all agree that the key objective here is to protect the patient. So people who use medicines expect that they will meet appropriate standards of quality, regardless of the reason why they are using that medicine. So there is a potential for harm to the patient if the medicines don't contain the right active ingredients and the right dosage, or if they contain harmful substances like pesticides, heavy metals, or microbiological contamination, or even if they are not manufactured, transported, or stored under the right conditions.

So when we're talking about quality standards, we can set quality standards under the scheme for a process or for a product. So we are proposing here to set quality standards for cultivation manufacture, the active pharmaceutical ingredients, and the finished products. We are going to be setting quality standards for all of these stages, but I just want to talk a wee bit about the quality standards for manufacture. Because as I said before, it's a key part of the quality assurance of the product.

So when we looked at what quality standards should be set for these products in terms of the manufacturing, there are two main options that we looked at. The first is the New Zealand approach for the manufacture of medicines, as outlined in the New Zealand Code of Good Manufacturing Practice. And I'll refer that now to refer to that now as GMP, because it's quite a bit of a mouthful to say.

GMP ensures that products are produced consistently and are of a reliable, high quality. So this is a system that we use for medicines in New Zealand. And it's based on an internationally-recognized system. Within Medsafe, we already have that system set up. We have a system of auditing, and we have staff that go out and they issue these certificates of GMP compliance.

The other system that we looked at, and was one that was flagged with us quite often by stakeholders, whether it's industry or patients, it's called GPP, Good Production Practices. And that's the approach that they've taken in Canada. So when we looked at the Canadian approach and GPP-- and I'll go into a wee bit about the differences now, but the Canadian approach does have a system for prescription medicines, similar to New Zealand. Prescription medicines are required to be manufactured to GMP. And like New Zealand, they are subject to pre-market authorization before they can be sold in New Zealand. Canada also have a category called non-prescription health products containing cannabis, which can be processed according to GPP.

However, this doesn't apply to manufactured medicines as we know it. It applies to certain classes of cannabis, which is the fresh and dried cannabis and cannabis oils. And in those classes, you can only have cannabis plant. So the fresh and dried can only be cannabis plant, and the cannabis oils are allowed to have a small amount of carrier oils. But essentially, the oils have to be derived from the cannabis plant. And later on this year, Canada will also be introducing regulation that allows edible cannabis and topical cannabis.

So what is the difference between these two from a technical point of view? So when we laid the two processes side by side, they were very similar. Both set out the principles that you have to comply with. But the difference is, with GMP, there is a code of practice, which gives you detailed guidance on how you might comply with that. So the way the codes operate is that you can have a code of practice, and if you follow the code of practice, then you are seen to be complying with the principles. However, the code doesn't say you must comply with the code. You can innovate, you can find another way of meeting those principles. But the onus will be on the manufacturer to prove that what they are doing also meets those principles.

Under GPP, we have those principles. And while the guidance is developing, there isn't clear guidance on how you might comply with those principles. That means the manufacturer has to decide how they are going to comply with those principles, but less detailed and open to interpretation. So the manufacturer will have to decide how they can comply with those principles. And on the others other end of the spectrum, the regulator then has to decide whether what the manufacturer is doing meets those principles. So on both sides, it's open to interpretation, but it's not as clear on what you have to do to meet those.

Another key difference is the validation program is required under GMP but not under GPP. And stability testing is required under GPP. So why is this important? What this key difference means is that the consistency of the product is not guaranteed. But the validation program means that those quality requirements are built into every step of the manufacturing process. So you have that assurance that what comes out of the other end is consistent, within a batch and between batches. So within the same bottle of pills-- so I can use that as an example-- every single dose is the same. And between-batch consistency means the batch that was produced a month ago is the same dose as a batch that is produced in three months' time.

Stability testing is, as some people know that with the cannabis-based products, some of it degrades over time, and there are changes to the key cannabinoid profile within the batches. So stability testing is very important. That tells you how long a product will last for in its current form. So the GMP production practices, manufacturing practices, are adopted by such countries as those in the EU, Australia, and Japan. Canada, at the moment, is the only jurisdiction that adopts the GPP approach. So the options here we have for manufacture are to adopt the New Zealand approach and require GMP for all products, or to adopt the New Zealand approach, but as with Canada, allow for some forms of products to be manufactured to GPP, as in Canada.

But also I'd like to reiterate that, in Canada, they still have a medicines regime similar to New Zealand. So the Canadian approach only talks about these specific product forms, fresh and dried cannabis and cannabis oils. So we're seeking information from industry on what the setup costs are, how long it will take to get products to market, and what the finished products costs are. And we're after a comparison.

So the other thing about GPP and Canada and these health products containing cannabis is they exist through these products or through a medical document from a doctor. So there's not a prescription. So this medical document authorizes the patients to access products through one of three ways-- to grow their own, to get someone to grow it for them, or to buy it directly from a producer. But that is only for those three forms of cannabis.

In terms of time to get products to market, we don't have that information. But we have asked for information-- we've asked industry to provide information on that if they can. But we also went to the Australians and asked them how long it took them to get products to market. Now, they implemented their regime in October 2016, and they're just starting to see the first products come through now. So that's 2 and 1/2 years since the scheme was implemented.

So we're going to learn from their experiences. And we've been talking to industry about how long it took them to get things to market, and what were the things that we could do to speed that up. So we think we can do better than 2 and 1/2 years, but we are seeking information on how we can make that easier.

So just a word on the finished dose forms under the scheme-- products for smoking will not be allowed, but we are going to allow products for vaping. What we consider to be the higher-risk dose forms, like modified-release dose forms and medicines that are required to be sterile, we are asking that they go through a proper risk assessment. So they'll only be allowed if they are approved or provisionally approved by the ministry. The Food Act does not allow products to be put in food that are prescription medicines. So food containing cannabis will not be allowed under the Food Act. Because there is no regulatory regime for natural health products, then cannabis-based dietary supplements, natural health products, and nutraceuticals must also meet the requirements of the scheme.

So I'd like to now hand it back to Chris to talk about the prescribing requirements.

Right. So the prescribing requirements, which I imagine will be quite of interest to this group. So what I'll just talk about is approved, versus provisionally approved, versus unapproved. And apologies if I tell you stuff that you already know. But I'll just go through it quickly for you. We'll go through what's not changing, and then the proposals that we're putting forward for change.

So to cover off, firstly, a couple of explanations. So approval, which you'll probably be aware of, is approval or conceit. It says conceit in the Medicines Act. We tend to use the word approval, because no one really knows what conceit means. Well, we do, but when we use that wording, it's not overly helpful sometimes. So we say it's approval to distribute a medicine. This is we're supporting information on clinical safety and efficacy as assessed by Medsafe and by the ministry.

And then we have an approval under the Medicines Act. There's also a provisional approval ability in the Medicines Act, and we've used this in the past. Well, we use it still currently. But it's a provisional early approval-- it can be. It can also be an approval that we use to put conditions on certain medicines. So we've used it in the past for things like antiretrovirals. So when there was a very high clinical need and the clinical data coming through was actually quite limited at the time, those medicines were given a provisional approval. We've also used provisional approval for [? Clonazepam ?] to ensure that it was a white cell count system in place, a monitoring system in place. So that's the way that you can actually enforce it as part of the approval of the medicine. So that's what we mean by provisional approval.

In terms of clinical need, if you have high clinical need and low access to a product, there is a case-by-case assessment that you might look at for what level of clinical data do you require to give a provisional approval. So is that preclinical, was it phase 2, is that phase 3? Where does that set?

And so around the world, there are a lot of new initiatives coming through from regulators that are looking at early access approvals. So Europe's got prime, the FDA had their 21st Century Cures Act, and Japan has the [INAUDIBLE] process, which is looking at either rolling submissions and approvals, or how you give an early approval, say, at phase II studies, with real-world evidence, post-market, coming through, which may then lead to a full approval. Our provisional approval provides this ability for us. Just something I wanted to explain to you.

The other point that we wanted to raise was about unapproved products, where safety, quality, and efficacy has not been assessed by the ministry.

Now, prescribing requirements that we're looking at is the no change. So looking at what we're not going to change-- CBD products, no change there. This is CBD products that meet the definition where they contain less than 2% of the cannabinoid THC or other controlled drugs or psychoactive substances. Obviously there is a change, which mean they came out of the Misuse of Drugs Act, but we're not looking at a change to prescribing. So approved or provisionally approved CBD products can be prescribed by a medical practitioner-- or a nurse practitioner, for instance-- any authorized prescriber.

Unapproved CBD products can only be prescribed by a medical practitioner. And for those wondering why that is, that's because we have a Medicines Act 1981. And when that was written, unapproved products could only be prescribed by medical practitioners. And we're currently looking at changing the Medicines Act and bringing in the Therapeutic Products Bill, which was actually out for consultation a couple of months ago. Obviously that's going to look to modernize prescribing and modernize our workforce and how we enable our health workforce for New Zealand. But that's, frankly, a couple of years away. So I just wanted to provide that background for you.

The other thing we're not changing is unapproved products. So unapproved products that aren't CBD products, so they are still controlled drugs that do not meet the quality standard. That is confirmed, obviously, by the end of the year. We're looking at no change to prescribing, which means specialists can prescribe, but you still have to come through the Ministry of Health for individual approval. Now, what are our proposals? And some of these proposals have had a lot of feedback, which is great. We've seen a lot of feedback in the media as well, both last week and also yesterday. This is all very helpful for us when we're looking at consultation and submissions.

Now, to break this down, approved products-- so these are approved medicinal cannabis products such as Sativex, that we have now. So on-label use is effectively when you're using a medicine that's approved for what it's approved for. So Sativex is approved for spasticity in multiple sclerosis, and it's called on-label use. Off-label uses is when you use Sativex for anything else, which is what you can do. And you can prescribe, and it's fine. But that's the difference between the two.

So for on-label use, we are proposing that they can be prescribed by any medical practitioners. But we will remove the requirement for specialist recommendation which we currently have in place. For off-label use, it can be prescribed by medical practitioners, remove the requirement for ministry approval, but specialist recommendation is still required. So at the moment, for off-label use for Sativex, every application has to come through the ministry. You need, for instance, your general practitioner to prescribe it. And then have a specialist endorse that. We're looking at the specialist recommendations still applying, but then you won't have to come through the Ministry of Health. Obviously keen for feedback on that.

Unapproved products that meet the quality standard-- and this is slightly different to when you use everything else unapproved. As a health care professional under section 29, unapproved medicinal cannabis products that we have assessed to meet the quality standard-- so they won't have all of the clinical data behind them-- we're looking for, can be prescribed by specialists, but remove the requirement to come to the Ministry of Health for approval. And also add the provision for medical practitioners to prescribe with a specialist's recommendation.

Now, just a bit of information about unapproved medicinal cannabis products. We are expecting, in the short term-- and some of this will be around industry gearing up once we have regulations in place and once cultivation and manufacture is happening-- that, in the short term, we expect it is likely to be mainly imported products, and with varying degrees of clinical information around the clinical efficacy and safety. Now, obviously, the research and the clinical studies are evolving. They're growing very quickly. We're seeing a lot of research in Australia, a lot of research in Canada and in Europe. We know that some products that are unapproved are in different phases of studies for particular indications. But at the moment, they are all unapproved apart from Sativex in New Zealand.

So the intent of the scheme is to make products easier to access by not requiring the full randomized controlled trial data package that you would have with a medicine. We understand it would be a major barrier to these products, but ensuring that we know the quality aspects of these products. So if you're looking to prescribe these, not only are we looking at providing information on evidence and how the evidence is coming through, and clinical studies are coming through around medicinal cannabis use, but making sure that the quality of the products, you know what you're prescribing, so you know what you're you talking to your patients about.

And that depends where the quality standard lands. So Andrea has talked about GMP versus is other quality standards. With GMP for instance, you know that the bottle of liquid, your spray that you gave to a patient, is going to be the same consistency and makeup as the next bottle. And that's under GMP. Whereas if you test a batch of product under a different standard, you may have batch-to-batch inconsistency. You may have levels going up and down. That's something we want feedback on from health care professionals, about how much reassurance do you want on these products to give you confidence to prescribe them and confidence to use them on your patients.

We're also seeking feedback on barriers to access and barriers to access for patients. So this is around prescribing requirements. We've obviously got a number of specialist recommendations in there-- is that an unnecessary barrier, do you think it should be in place? Really keen for feedback on that.

The consultation period-- next steps are-- so this goes for four weeks, until the 7th of August. We know this is short. We tend to go out for consultation a lot longer than that. But as I mentioned, 18th of December is hurtling towards us. We've got 12 months to do this, so we've had to do this in four weeks, and that's why we're coming out and going both to Auckland, Christchurch, and Wellington, to hold sessions and informed submissions, and get as much feedback as we can.

Stakeholder groups, I've talked about, who we're going to go in and talk to directly. We'll also be targeting some groups. We're going to the provisional bodies. And depending on who attends our health care professional sessions, we'll be wanting to talk to, for instance, Royal College of GPs, be talking to various medical professional bodies. We'll also be talking to the pharmacy professional bodies, the Pharmacy Counseling Society, et cetera.

The next step, really, is we have a Medicinal Cannabis Advisory Group, which that has around 13 members, and has representation of our consumers, and for industry, and for health care professionals. So it's chaired by Russell Wills, who is a pediatrician from the Hawke's Bay, ex-children's commissioner. And they've helped us to craft the consultation document, and to fine-tune it, and give us advice.

We'll be going back to them with what we've seen, key themes from the consultation process, and help to arrive at what are our actual regulatory proposals, that we'll be then putting up to cabinet for approval of draft regulations in October, and for cabinet to approve those regulations in December, by the 18th of December.

We then expect-- so as far as the legislative process goes, you then have a 28-day-- what's effectively stand-down period, which then takes us into [INAUDIBLE] in January. We also have, obviously, a close-down period over holidays. We are looking at implementing this scheme as soon as possible after that, after the 18th of December.

Now, you can't confirm everything until you have approved regulations. Because if regulations change, and you've done an awful lot of implementation, you need to change it all. But what we're doing is trying to run our regulations process and our implementation process in parallel as much as we can, because we want to have this in place as quickly as possible. And we're looking for the first quarter of 2020 to be able to receive applications.

Thank you. That's all we have to talk to you about at the moment. Very keen to have you feedback. You can do that through an online tool on Ministry of Health website. If you go onto the Ministry of Health website, health.govt.nz, and put medicinal cannabis into the search field in the top right corner, it comes up with all the documentation and all the consultation information, and how you can make a submission. Let us know what you think. Thank you.