Webinar presentation: SME Assist - Meeting your obligations - Supplying medicinal cannabis in Australia, 21 October 2021

Steven Smith-Fleury

My name is Steven Smith-Fleury. I work in the SME Assist team here at the Therapeutic Goods Administration. Just before we do start today, I'd like to acknowledge the traditional owners and custodians of the lands on which we meet today and pay my respects to their Elders past, present and emerging. I'd also like to extend that respect and acknowledgement to any Aboriginal and Torres Strait Islander peoples joining us today.

Just a disclaimer before we do start, please just note that these slides are a summary only and that they shouldn't be taken as law or policy.

Today's training session will consist of a few different parts. 

Part one will cover the basics of therapeutic goods' regulation. This will provide an overview on how therapeutic goods are regulated, what we do at the TGA, and we'll cover some terms that you'll need to know and also where to find help if you need it. 

Part two will cover supplying medicinal cannabis. This is where we'll look at that specialised part of today's workshop. We'll cover supply as a prescription and over-the-counter medicine. And we'll also hear about both the TGA and Office of Drug Control's requirements on manufacturing and importing. From there, we'll have a short break and then we'll be back for part three, which is a Q&A session with TGA experts and we'll spend an hour in that Q&A.

As I said, we will start with the basics of therapeutic goods' regulation, where I'll give you general information about the therapeutic goods' regulation in Australia, the role of the TGA, TGA's SME Assist service and how to supply medicinal cannabis in Australia. I'll also point you in the direction of where you can find some help if you do need it.

We do understand that therapeutic goods' regulation can be challenging to navigate. We provide the SME Assist service at the TGA to help small-to-medium enterprises, start-ups, researchers and anybody, basically, who's unfamiliar with therapeutic goods' regulation, to understand their responsibilities when it comes to supplying therapeutic goods. Our team runs workshops which cover the basics of regulation, market authorisation, manufacturing, advertising and post-market monitoring. We have recorded and published some of our livestreamed workshops and also have pre-recorded material available for you. You can find all of this on the TGA website under educational videos or on the SME Assist hub of the TGA website too. We do have a range of interactive decision tools to help with decision making when it comes to supplying therapeutic goods. These include, 'Is my product a therapeutic good?' Just as it sounds, that decision tool will help you determine whether or not your product is a therapeutic good or not. And another tool that we do have available amongst others is, 'What classification is my medical device', in case you're looking at supplying a device. We do encourage you to subscribe to our SME Assist email list to stay up to date with the latest SME information, including any upcoming workshops, new guidance and webinars. I will mention here also that we have recently released a series of five podcasts just around therapeutic goods' regulation. We cover things like what happens in the laboratories, advertising of therapeutic goods and manufacturing, amongst other things. You can find that podcast wherever you listen to your podcasts. It's available on all platforms now, also on the TGA website.

We'll start now with the basics of therapeutic goods' regulation.

First, we'll have a look at the TGA, of course, who we are and what we do. We are a part of the Australian Government Department of Health. We regulate and monitor all therapeutic goods to ensure that they're safe, of good quality and do what they're supposed to do. We do this in line with the Therapeutic Goods Act, which provides a uniform national system of controls over therapeutic goods. And this system, of course, is of benefit to both consumers and industry.

When we're looking at what a therapeutic good is, what do we mean by a therapeutic good? A therapeutic good is broadly defined as something that's used for preventing, diagnosing, curing or alleviating a disease, ailment, defect or injury, for example, a medicine like paracetamol. A therapeutic good may influence, inhibit or modify physiology, for example, a pacemaker. It could be used to test for a disease or ailment, something like an MRI machine potentially. It can influence, control or prevent conception, for example, a condom. It can test for pregnancy, so a pregnancy test. It could also replace or modify a part of the anatomy, for example, a prosthesis. Again, we do have those decision tools available on our SME Assist webpage to help you determine if your product is a therapeutic good. And again, in the case of a device, the classification that it might be.

Therapeutic goods generally fall under three categories. We're looking at medicines, biologicals and of course, medical devices. First, we'll have a look at medicines. Within that space, we've got prescription medicines like antibiotics. And these require a doctor's prescription. We've got complementary medicines which contain herbs, vitamins, minerals, nutritional supplements, homeopathic and certain aromatherapy preparations. For example, here, we might be looking at multivitamins, some herbal teas and also potentially some essential oils. And then we've also got over-the-counter medicines. These can be purchased without a prescription and they're also not considered complementary medicines. They include things like some lozenges and also some cold and flu tablets. Medicines also include things like vaccines, blood and plasma. The second category we'll have a look here are biologicals, which are things that are made from or contain human cells or tissues or live animal cells, tissues or organs. An example might be a skin graft between patients. And finally, we have medical devices. They have a physical or mechanical effect on the body and are used to measure or monitor bodily functions. They can include things like surgical tools, appliances like pacemakers and materials like sterile bandages.

It's also important to know what the TGA doesn't regulate. We don't regulate veterinary medicines. We don't regulate health professionals or health insurance. We don't regulate food standards. And we don't regulate cosmetic and chemical standards. These are regulated by other federal or state and territory bodies. You can see some of those here on this slide. Do note that some cosmetics used in surgery, for example, things like breast implants and cosmetic injectables are actually regulated by the TGA. And it's also worth noting we do sometimes interact with other regulators. If you do work with us, you may also need to work with other regulators.

At the TGA, also we don't research or develop new therapeutic goods. We don't provide clinical advice to individuals or consider cost-effectiveness or recommend one product over another. And we don't make decisions about subsidies of therapeutic goods.

Here, we have an overview of the therapeutic goods' development lifecycle to show you how the different stages do fit together. First, if you're looking at conducting a clinical trial, you'd design and get approval to run that trial. Then you'd get approval to use your unapproved product in the trial. And then you'd also seek approval to supply your product after that. That's known as market authorisation. And then during that, you'd also potentially look at possible subsidisation of your product. Here, you can see that the TGA is responsible for the use of your unapproved product in a clinical trial and approving the supply of your product. You can see that in the blue boxes here. TGA isn't responsible for designing clinical trials or subsidising therapeutic goods. You can see those things in the green boxes here. And I'll just note the subsidisation is carried out by our colleagues over at the broader Department of Health. For some products, you may be able to make applications to the department for subsidy, in parallel with your application to the TGA for market authorisation. However, no pharmaceutical prosthesis or Medicare listing will occur until the product is actually included on the Australian Register of Therapeutic Goods or ARTG. For more information around this, you can contact the Pharmaceutical Benefits Scheme or have a look at their website. You can also check the Prosthesis List Advisory Committee website or the Medical Services Advisory Committee website. And do remember that TGA approval doesn't necessarily mean that your product will be subsidised. We might just move on now and have a bit more of a closer look at clinical trials and our involvement there.

In Australia, the clinical trial environment is quite broad. Clinical trials conducted here are subject to various regulatory controls to ensure the safety of participants. All clinical trials require ethics approval before they can commence. And trials that do involve the use of unapproved therapeutic goods are also subject to TGA requirements. While the TGA is not heavily involved in clinical trials, our two pathways for accessing unapproved therapeutic goods for experimental purposes, first of all, the notification process called the CTN scheme. And this is for lower risk products. And then for some high-risk or novel treatments, such as gene therapy, we've got the approval process, which is called the CTA scheme.

The use of unapproved therapeutic goods in a clinical trial must be in accordance with national and international guidelines and of course, the protocol approved by the relevant human research ethics committee.

Our Australian clinical trial handbook provides guidance on requirements when conducting clinical trials using unapproved therapeutic goods. It does help those involved to understand their roles and responsibilities under our legislation. And you can see more information on the responsibilities outside of TGA requirements if you visit the National Health and Medical Research Council, Australian Clinical Trials website. For any further information or clarification on our Australian clinical trial handbook, you can always get in touch with us via telephone or email, of course.

We'll move on now to market authorisation. Market authorisation is required, of course, before you can supply a therapeutic good in Australia. When we look at supply, we're not just looking at selling a product. Supply is the sale, exchange, gift, lease, loan, hire or a hire purchase of the product. We're looking at things here like potentially a free sample, the leasing of a dentist drill, hiring out crutches. All of those things and all of those activities would need market authorisation. If you want to manufacture, import, export or arrange for the import, export or manufacture of therapeutic goods, you will need to apply for market authorisation.

When authorisation is granted, the product would be added to the Australian Register of Therapeutic Goods or ARTG. I have mentioned this a couple of times already. The ARTG is an online database on the TGA website, where you can search using keywords. You could potentially search for a product name, an active ingredient, a sponsor name as well. There's a number of search terms that you can use. It is a good idea if you are applying for market authorisation that you do search the ARTG to see similar products that are being supplied.

Each ARTG entry is unique in some way or as we call it, separate and distinct. This uniqueness depends on the type of therapeutic goods you have. You can see here and you will have received the slides for today. You can go to the relevant links here and have a look at the definition in the legislation that's relevant to your product. For now, we'll just have a look at a high-risk prescription medicine as an example. If we have another medicine that is exactly the same, but has a different name, a different indication or different dosage, that product would be considered separate and distinct and it'll have its own ARTG entry in that case. But if it has just a different pack size, for instance, for example, a 12-pack of tablets versus a 36-pack of tablets, it's not considered separate and distinct and a separate ARTG entry would not be required in that case.

When we are assessing your product for market authorisation approval, we do use a benefit versus risk approach. Goods that do pose a higher risk of adverse events or are used for more serious diseases like prescription medicines, are more tightly regulated than those that pose a lower risk like herbal supplements. Each therapeutic good will have different degrees of benefit and risk but in all cases, benefits must outweigh the risks.

We'll have a look at benefit versus risk in the context of medicines here. As you can see, medicines are considered low- or high-risk depending on the claims made about the medicine, what it contains, the benefits and risks associated with it. In Australia, lower risk and higher risk medicines are given particular names. Lower risk medicines are called listed medicines. Higher risk medicines are called registered medicines. And anything in between those are called assessed listed medicines. The take-home message here, I guess, is that higher risk registered medicines do require more rigorous pre-market evaluation.

Our work at the TGA is ongoing. It does continue over the lifetime of every therapeutic good, from manufacturing through to adverse events.

Our regulatory compliance functions do support consumer protection and enable a fair market for industry. We monitor and enforce where necessary compliance with legislation, regulations and rules for therapeutic goods. We do promote high levels of voluntary compliance through engagement and education as well.

All types of therapeutic goods do have their own Australian regulatory guidelines to assist applicants and sponsors with the process of applying for market authorisation. These are listed on the slide here, as you can see. Do note that they are guidance documents only. But you can access them through the links shown on the slides. If you do access them and need any help with them, if you're not sure what something means in there, you're more than welcome to give us a call here or, of course, pop us an email.

The Australian regulatory guidelines are located in the industry tab on the TGA website. The different types of therapeutic goods are listed underneath, as you can see. Here, you select the standards and guidelines and then you'll find the relevant guidelines for the type of products that you're looking at supplying. You can see there, we've got prescription medicines, over-the-counter medicines, complementary medicines, as well as sunscreens, medical devices and so on.

The TGA Business Services is where you'll submit and manage your applications. Every sponsor does need an account for the TGA Business Services portal and you would create an account by completing an organisation details form, which you can find on the TGA website. You complete that form and send it back to the email address on the form itself. If you do need any help with that at all, again, please don't hesitate to get in touch with us here.

Fees and charges, we do cover costs through fees and charges for activities that fall within the scope of the Therapeutic Goods Act. As a sponsor of a therapeutic good, you will be required to pay fees and charges that apply to your good. Fees are for a service, while charges of course are an annual tax. All therapeutic goods on the ARTG are subject to annual charges, except for export-only products and products that fall under the annual charge exemption scheme. We do encourage you to have a look at the link to fees and charges so that you do know what to expect.

I did mention the annual charge exemption or ACE scheme. This allows for the exemption of annual charges until a product first generates turnover. All new entries on the ARTG are eligible and sponsors would need to make a declaration each year confirming $0 turnover. We do note that fees are not included in the annual charge exemption scheme, only charges. And I will just note here also, if you do have a product that doesn't make turnover in the first couple of years and then it does, you'd no longer be eligible for the ACE scheme, even if in the future it doesn't generate turnover.

The SME Assist hub, you can find a range of information on the SME Assist hub under the industry section of the TGA website. As you can see here, you can click on that section on the front page there. You can also go to the industry tab of the TGA website and you'll see SME Assist at the top of the page there. We'll now take you through some of the aspects of supplying medicinal cannabis in Australia.

Please do note that we will briefly cover access to unapproved medicinal cannabis products. But our focus will be on domestic supply of products included in the ARTG and the pathways through which this can be done.

As we've already learnt, all therapeutic goods, unless exempt or excluded, must be included in the Australian Register of Therapeutic Goods before import into, export from or supply in Australia. This includes medicinal cannabis products when for general supply in the marketplace. There are also particular circumstances in which approval is granted for the use of unapproved products. And we'll touch on that now.

Medicines that are not included on the ARTG are known as unapproved medicines. With these products, it is really important to note that the TGA has not evaluated them for safety or efficacy. As far as accessing these goods, any Australian medical practitioner can apply to supply these products via the Special Access Scheme or SAS or the Authorised Prescriber Scheme. The Authorised Prescriber Scheme, under that scheme, medical practitioners can apply to supply a specific unapproved medicinal cannabis product to specific patients, patients with a particular medicinal condition or symptom. As far as the Special Access Scheme, medical professionals can apply to prescribe these products for any particular indication. As far as actually making application, health professionals would lodge their Special Access Scheme application or Authorised Prescriber Scheme application through the online SAS or Authorised Prescriber online system. They may need to also make application to relevant state or territory health departments. But we do have an arrangement in place with the online portal now where we can submit those in tandem. Anyone supplying medicinal cannabis through these schemes, what would be known as a sponsor, is responsible for meeting their regulatory requirements. This would include the submission of the TGO 93 declaration form. The Therapeutic Goods Order 93 or TGO 93 is a standard that specifies minimum quality requirements for medicinal cannabis products. That would need to be submitted to the TGA. More information about these processes is available on the TGA website or you can contact us by telephone or email again. The government's ultimate goal is to have a wider range of medicinal cannabis products included in the ARTG as registered medicines. We're now going to move on to general supply of medicinal cannabis or those products requiring inclusion on the ARTG.

First of all, our first stop, of course, is to look at the scheduling of products. Scheduling of medicines plays an important role when supplying medicinal cannabis. The Poisons Standard has been developed to ensure the safe handling of substances in Australia. It does provide a uniform approach to control the availability and accessibility of substances that can be used as ingredients in medicines, as well as cosmetics, agricultural products or household cleaners. It also includes provisions about containers and labels, with a view to promoting uniform labelling and packaging requirements through Australia. The Poisons Standard is given legal effect through state and territory legislation. It's also known as the Standard for Uniform Scheduling of Medicines and Poisons or SUSMP. As I said, the different states and territories may give that different legal effect and it's always good to check with them also. Medicines and poisons are classified into schedules as shown here on the slide. For our purposes, we're looking at Schedule 3, which is for a pharmacist-only medicine. Schedule 4 is prescription-only medicine. And Schedule 8 is for controlled drugs. You can find more information about scheduling on the TGA website. And we do have a link in the slides today. Again, you can contact us if you need assistance.

If we look at cannabis and the cannabis scheduling, cannabis and its derivatives do appear in Schedules 3, 4, 8 and 9 of the Poisons Standard. For our purposes today, though, we'll be looking at Schedules 3, 4 and 8, as Schedule 9 substances cannot be used in therapeutic goods. The first things that we'll look at here are cannabis and tetrahydrocannabinol or THC. As you can see from the slide here, under certain circumstances, cannabis and THC are controlled drugs and appear under Schedule 8 of the Poisons Standard when prepared or packed for human therapeutic use. Access will need to be confirmed with relevant state or territories, as this can vary between jurisdictions. The next substance that we'll have a look at here is cannabidiol or CBD. Cannabidiol or CBD can appear in Schedules 4 or 3. For the Schedule 4 entry, it is in preparations for therapeutic use or analytical and scientific research when it comprises of 98% or more of the total cannabinoid content of the preparation. And any other cannabinoid other than cannabidiol, must only be those found naturally in cannabis and comprise of 2% or less of the total cannabinoid content of that preparation. It would not be included Schedule 4 when it's included in Schedule 3. And we'll have a look at that now. A Schedule 3 entry for CBD or cannabidiol is a low-dose CBD entry. It is for oral oromucosal and sublingual preparations included in the ARTG when the cannabidiol is either plant-derived or when synthetic, only contains a certain enantiomer. And of course, the cannabidiol comprises 98% or more of the total cannabinoid content. And there's a couple of other requirements there, including specific restrictions on dose, packaging, pack size and intended uses. And I'd suggest having a look at the Poisons Standard or SUSMP, just to have a look at the different entries there if you are looking at supplying a product to see where your product might sit. We do have other substances as well. As you can see on the slide here, we do have nabiximols, nabilone and dronabinol, which are listed as controlled drugs as well. That's Schedule 8 of the Poisons Standard. Any Schedule 8 controlled drug does require a prescription from an Australian registered medical practitioner. And there may be certain state or territory requirements as well.

We'll move on to manufacturing requirements. First of all, we'll take a look TGA manufacturing requirements under the Therapeutic Goods Act, which are different to the requirements of the Office of Drug Control, which we will cover a bit later. Therapeutic goods must be manufactured by a TGA-approved manufacturer. When we look at manufacture, we're looking at anything from packaging, labelling, processing, testing, release for supply and some other steps that are listed on the slide here. All manufacturers must comply with the principles of Good Manufacturing Practice or GMP. That's a term that you'll hear quite often. GMP or Good Manufacturing Practice, describes a set of principles and procedures, which when followed by a manufacturer of therapeutic goods, helps to ensure that each batch of a therapeutic good is safe, reliable and of consistent high quality. Manufacturers must obtain a GMP licence or clearance for the manufacturing steps that they perform and also the type of medicine. The TGA website, which includes a step-by-step guide around manufacturing medicines. And you can also refer to the decision tool on the SME Assist hub. This can help you determine whether you're looking at requiring GMP licencing or certification. And we'll go into the different types of requirements now.

There are different processes that apply for obtaining approval for manufacturers in Australia compared to overseas. If your manufacturer is located in Australia, they'll need to obtain a GMP licence from the TGA. They'll have to submit a GMP application to us with the details about their manufacturing sites and their manufacturing steps. This would involve an on-site inspection and after the inspection and after the application's assessed, if a licence is granted, the manufacturer would then forward these licence details through to the sponsor for them to include in their market authorisation application. At the end of the day, the sponsor is considered responsible for ensuring that their manufacturer does have a GMP licence. It is important to note as well that manufacturing inspections can happen at any time during the market authorisation process to ensure compliance. If your manufacturer is located overseas, it would be the sponsor's responsibility to ensure that they have GMP clearance as opposed to a GMP licence. We do have various international agreements and arrangements with other countries and jurisdictions. These are called Mutual Recognition Agreements or MRAs. For medicines and biologicals, there are around 25 countries that we do have an MRA with or an equivalent arrangement with Australia. You can find a list of these countries on the TGA website. Do have a look there. Again, if you need any assistance or guidance there, you can always get in touch with us. Again, if your manufacturer is located overseas, you do have a few options as far as obtaining GMP clearance. The first, of course, would be the Mutual Recognition Agreement or MRA pathway, which you could use if your manufacturing site is within the borders of an MRA country and your site has been inspected by that country's regulatory authority. The second would be the compliance verification pathway, which you could use if the manufacturer doesn't meet criteria for MRA and the site has been inspected by an MRA regulatory authority. And the third and final would be the GMP certification pathway. You could use this pathway if the MRA or CV pathways are not applicable or if there's no acceptable evidence from a recognised regulatory authority available. This pathway may also involve an on-site inspection by one of our GMP inspectors. The GMP clearance application assistance tool on the SME Assist hub will help you determine the general evidence requirements for your GMP application. If you go to the TGA website, again under industry and select SME Assist, go to the interactive decision tools and you'll find that tool there. Again, if you do need assistance with the tool or anything to do with GMP requirements or TGA's manufacturing requirements, you can always give us a call, send us an email or send your inquiry direct to the GMP team. There's contact details at the end of these slides.

We'll have a look at requirements from the Office of Drug Control. The Office of Drug Control is part of the Department of Health. ODC regulates and provides advice on the import, export and manufacture of controlled drugs, as well as the cultivation of cannabis for medicinal purposes, to support Australia's obligations under international drug conventions. A medicinal cannabis licence authorises either cultivation, which is the growing of the cannabis plant, or the production, which is the separation of cannabis and cannabis resin, or both. There are no restrictions on the number of licences that can be granted. However, under international conventions, the overall quantities produced must not exceed domestic requirements. We've also got a cannabis research licence. A cannabis research licence authorises the cultivation and/or production of cannabis for research related to the medicinal use of cannabis. In order to obtain a cannabis research licence, an applicant will need to explain the purpose of the research and of course, how it relates to medicinal cannabis and/or medicinal cannabis products. In all cases, the licensee will need to hold a permit issued under the Narcotic Drugs Act before any cultivation or production commences. For further information on the role of the Office of Drug Control in the supply of medicinal cannabis in Australia, you can find some really helpful information on their website. That would be www.odc.gov.au. We will provide the links here as well. Or by contacting them on the details that we'll provide.

Import and export of medicinal cannabis products between countries, including those made from low THC cannabis, is tightly controlled and subject to international drug conventions. Approval must be granted by the national governments at both the importing and exporting countries before shipment can occur. As far as import into Australia, if a medical practitioner considers a medicinal cannabis product suitable for a particular patient, they can either apply through the Special Access Scheme, as we discussed earlier, or the Authorised Prescriber Scheme. These schemes do relate to unapproved therapeutic goods. If we have a look at the export of therapeutic goods, provided the domestic supply of medicinal cannabis isn't affected, some products are eligible for export if a licence and a permit to export are granted. Here, we're looking at things like Australian manufactured medicinal cannabis products that are manufactured under a GMP licence. Also, medicinal cannabis products that are listed as export-only or registered on the Australian Register of Therapeutic Goods or ARTG. Extracts of cannabis or extracts of cannabis resin manufactured under a Narcotic Drugs Act of 1967 licence and permit that are not in the form of the finished product may also be eligible. Really, if the product doesn't appear on the ARTG either as an export-only or registered medicine or a licence and permit to export the drug hasn't been issued by the Office of Drug Control, it wouldn't be permitted for export. If we look at wholesale, a person who supplies unregistered medicinal cannabis products by wholesale is likely to contravene the Therapeutic Goods Act of 1989. Those contraventions may result in a regulatory action under the Therapeutic Goods Act and can also have implications for licences issued under the Narcotic Drugs Act. Customs that prohibited imports regulations and also state and territory legislation. It's important to have a look at the information that we do have available on our website around supply and wholesaling of medicinal cannabis products.

If we move on to supply, sponsors can submit an application to include Schedule 4 CBD preparations in the ARTG, which are regulated as prescription medicines. Applications are individually evaluated for safety, quality and efficacy and must meet all legislative requirements for therapeutic goods as set out in the applicable legislation.

Information on the application process and data requirements is available in the Australian Regulatory Guidelines for Prescription Medicines. And currently, there are only two products approved. I'm now going to hand you over to Klara Koelmeyer, from our prescription medicines team, to briefly take you through the application process. Over to you, Klara.

Klara Koelmeyer

Hi. Thanks, Steve. You can hear me okay?

Steven Smith-Fleury

Yes, we can hear you.

Klara Koelmeyer

Thank you. I will be talking about the prescription medicines' registration process, which outlines a number of different processes for prescription medicines. We have different application types, different categories and they are all fairly detailed. As Steve had mentioned, you can refer to the Australian Regulatory Guidelines for Prescription Medicines or you can always contact the application entry team and myself and my team will always help out with any questions, if need be.

For prescription medicines, there are different pre-application activities that you may consider before applying for a prescription medicine application to go through the process. There's also things to consider like the approved terminology for medicines and ingredient names. Then this is a requirement before applying for a prescription medicine. This will also determine the type of medicine it is, will determine the scheduling as well and whether or not it will have to come through the prescription medicines process. There's a number of options available as well, such as pre-submission meetings. At a pre-submission meeting, you can discuss with the relevant clinical evaluation areas and all the other experts within our branch about your proposed pathway forward and if you've got any questions before you actually put in an application. All of our prescription medicine applications will require a product information document to be submitted or a draft PI at the time until it is approved, a Consumer Medicine Information document as well. And then you would also need to consider patent certification, information and data exclusivity. Data exclusivity for a new chemical entity is outlined in Section 25A of the Therapeutic Goods Act. And it does talk about a five-year data exclusivity period from the registration of the new chemical entity. The patent certification is required at the end of the process before the product is actually put on the ARTG and that's outlined in Section 26B of the Therapeutic Goods Act. But again, I know this is all a lot of detail to take on board. Please do contact us for more information, especially about pre-submission meetings and any pre-application requirements.

The different categories that we have within prescription medicines is Category 1 applications, they're our highest application category and Category 1 applications do contain a number of different application types within that category, the highest one being a new chemical entity or a new biological medicine application. And then we can go into an application type for an extension of indications. If you already have a medicine on the ARTG and you wish to extend the indications for that medicine, then that's our next highest category. We also then have major variations where you may want to register a new strength or consider a new dose form. All of these are Category 1 submission applications. And even things such as changes to the clinical aspects of the product information document may require a Category 1 submission to be submitted. Category 1 submission does require clinical evaluation and at times, toxicology and quality information and that's why they have the longer statutory timeframe of 255 working days, which is legislated. But then we can also consider a comparable overseas regulator category, which may reduce the timeframe. And I'll move on to the next slides to actually detail that process a bit more. But it may reduce the legislated timeframes down to 120 working days. Category 3 applications and minor variations are usually a standard 45-working-day legislated timeframe. And just as the name implies, the minor variations, it's minor changes to your registered good. Category 3 applications may be things like changes to shelf life and manufacturer information, for example and do not have clinical or toxicology data. The statutory processing times are outlined in the regulations and that's why they are legislated timeframes. I've already mentioned the different application types that we have for our Category 1 submissions.

These are some of them just outlined on the slide. And even things like new generic medicines are incorporated within our Cat. 1 applications, as long as you're able to provide bioavailability data and all of the required information for a new generic medicine.

The key phases or milestones for a Category 1 application is, we have a pre-submission stage. And this is different to a pre-submission meeting. A pre-submission meeting occurs outside any of the application processes, whereas the pre-submission stage is what generates and initiates your application. This is what is required. Once you've actually registered as a sponsor and you have your client ID, you can then go onto the TBS portal and submit a pre-submission application and follow the processes at that stage. With a pre-submission application, it is mainly just to generate the submission number on our workflow system. And then the next step, the submission step, is where the dossier is provided. And the dossier is what includes all of the required information that we need to determine whether or not your application is actually acceptable for evaluation. This is just that determination stage to determine whether or not we will accept the application for evaluation. The rest of the steps then are what happens throughout the evaluation process. We may reach out and our section 31 questions and then follow the process through to the TGA decision. And then the administrative aspects of the post-decision process and writing the product onto the ARTG if the evaluation or the product is approved.

This is the comparative overseas regulator applications, which we used to call Category 2 submissions. They may have a reduced timeframe of 120 working days or 175 working days, depending on what part of the criteria you can meet. There is certain criteria that you do have to meet, such as that the application must be exactly the same in the comparable overseas regulators as well. We've got the countries listed on the slide that we do accept evaluation reports from. But the criteria doesn't stop there. The criteria means that the same application should have been submitted and the same evaluation must have been completed by those regulators. They're not very common, but they are becoming a lot more common as we start working closer with our overseas counterparts. Criteria for full submissions is that it should be a Category 1 submission. This criteria does not apply for any of our minor variations.

Over the last few years, we have been trying to streamline our processes and trying to minimise the 255-working-day timeframe. And as a result, we've introduced a number of various pathways to accompany our Cat. 1 application, N4 application pathways. The priority review pathway does allow for a faster assessment of eligible prescription medicines. But there is a determination step that is required prior to submitting an application. And that this step also requires an application through our TBS portal and there is a very strict criteria that the sponsor would have to meet to be able to receive a priority determination application. If priority determination's granted, then you may proceed with your Category 1 submission, with that priority pathway and the evaluation timeframes will be significantly reduced.

As a result, we've also introduced the provisional approval pathways, which allows the sponsors to apply for time-limited provisional registration on the ARTG. The timeframe is specific and eventually, after a number of years and extensions, if possible, you will be able to submit all of the data required to have the product fully registered on the ARTG. There is always a transition from the provisional to full. But the provisional pathway does provide earlier access to certain promising new medicines. And again, it does require the determination step prior to submitting the Category 1 submission. And it does have an even stricter criteria where our team of clinical experts within our prescription medicines authorisation branch will assess all of the determinations for provisional application submitted to us and make sure that all of the eligibility criteria are met before the provisional approval is provided.

There's also requirements and the way we deal with our dossiers, because they are very complex and our evaluation areas need to know where to find specific information. We do specify and require that all of our applications' dossiers are submitted in the Common Technical Document format and that they do meet all of the general dossier requirements. We are still accepting NeeS, non-eCTD submissions to the TGA. But please know that this is very quickly transitioning to full eCTD requirements. And all those requirements, they are very detailed. Again, there's links on our website provided. But if you do have any questions, do reach out and we will explain anything at all. But basically, the eCTD common technical requirements do specify that there are certain modules that you have to provide. And each one of those modules determines what type of application is within those modules. For example, module 1 will have all your administrative aspects, whereas module 3 will have all the quality information and then module 5 will be your clinical information. But as I said, this is all specified in the common technical data requirements.

There's more information on our website and there's quite a bit of information. And especially with the introduction of our new provisional and priority determination pathways in our orphan criteria, it's probably best just to refer to all of these links. And then if you don't understand any of those aspects, do reach out to the application entry team and we'll be more than happy to answer any questions.

I guess the final hints and tips is just to ensure and check that your product is a therapeutic good, a Schedule 4 for a prescription medicine, for example. Decide whether you want to have it approved in your name to supply in Australia. Because if this is the case, then you must be a registered client within our client database.

And also note that you will have all regulatory activity responsibilities for that product once it is on the ARTG and obviously throughout the evaluation process. Understanding the legal requirements for the product and your legal responsibilities. And basically, determining if it meets a particular submission pathway and application type. That can often be a little bit complicated. And we do receive a lot of inquiries through the application entry inbox about whether or not a particular submission pathway is appropriate and what the application type should be. And we do encourage sponsors, before they submit the actual application through the portal, to discuss whether or not this is the right application with us, as we would like to ensure the smooth transition of any application processing for both sides.

At the end of it, we will publish what we call the AusPAR, which provides a summary of the submission and the TGA's evaluation of the company data submitted. The considerations and what led to the decision-making process for the TGA to approve or not approve an application. We may have AusPARs on the system as well for rejected goods, but there is a lot of negotiation that goes on with our sponsors in relation to this. But one thing to consider is just that the AusPAR is what we call a summary of the evaluation process. It obviously doesn't detail the whole evaluation pathway. And I think that's me done, Steve.

Steven Smith-Fleury

Thank you for that, Klara. It's really great. Now we're going to have a look at supply of medicinal cannabis as an over-the-counter medicine. Just a bit of background, on 15th December 2020, a final decision was made to down-schedule a certain low-dose cannabidiol of CBD preparations from Schedule 4, which is a prescription medicine, to Schedule 3, which is a pharmacist-only medicine. The final decision was that low-dose CBD products containing up to a maximum of 150 milligrams per day and for use in adults 18 years and over and used in oral mucosal and sublingual preparations, that are packed in blister or strip packaging or in a container with child-resistant closures and containing no more than 30 days' supply in a pack. And that meets specified formulation requirements in that the cannabidiol that is either plant-derived or when synthetic, again as we discussed a little bit earlier, only contains that certain CBD enantiomer. And it also contains cannabidiol that comprises of 98% or more of the total cannabinoid content of the preparation. Any cannabinoids other than cannabidiol in these preparations must be those that are only naturally found in cannabis and can only comprise of 2% or less of the total cannabinoid content of the preparation and of which tetrahydrocannabinol or THC can only comprise of 1% of the total cannabinoid content. And those products would need to be approved by the TGA and included on the ARTG. Those products, as per that determination, can be supplied as over-the-counter medicines by a pharmacist without a prescription. It is important to note that there may be other requirements set out in legislation, including complying with advertising requirements and displaying any required warning statements on packaging as well. I'm now going to hand you over to Kevin Eager from our over-the-counter medicines space to take you through the application process for over-the-counter medicines. Over to you, Kevin.

Kevin Eager

Thanks, Steve. In order to get an OTC medicine registered on the ARTG, the sponsor must submit an application to the TGA. There are various application levels to register a new OTC medicine, ranging in complexity from the N1 application pathway at the most simple level, to N5 at the highest or the most complex level. An application to register an OTC CBD medicine needs to come in at the N5 the application level. These are non-generic medicines and fully evaluated for safety, efficacy and quality. There are guidance documents on the TGA website, specific for OTC medicines, which detail the application process, application formatting requirements and data requirements.

The data are provided in CTD format. As Klara said, that's the Common Technical Document format. Guidance on the format of an application is included on the TGA website. In summary, the data are provided in five modules. Modules 1 and 2 comprise the administrative and the summary data. Module 3 includes the quality data. An important point to note here, in addition to the usual OTC module 3 data requirements, which are outlined on the website, CBD applications along with many other N5 level applications, will also be required to include a module 3.2.S component. Or if the product is manufactured, the drug substance is manufactured by a third party, then a DMF, which is a drug master file. This provides important information on the drug substance itself such as information on the manufacture of the substance, classification and stability. The module 4 data, the module 4, includes the non-clinical data. That includes toxicology data and pharmacokinetic data.

The module 5 includes the clinical data. The clinical data on the formulation proposed for marketing in Australia as expected, this should also include dose-ranging studies to identify the minimum effective dose which is specified for your product and specific for the therapeutic indication. Due to the lack of high-quality published trials, any literature submitted as part of an application is likely to be supportive at best. Further, the relevance of the studies and the literature to the proposed product would need to be demonstrated. All literature searches must be systematic searches. There's guidance on the TGA website on conducting a literature search.

The data supporting the safety and efficacy of the product must be relevant to the proposed therapeutic indications, the patient population and the proposed dosage. The therapeutic indication, including any claims made on the labelling of the product, must be suitable for a pharmacist's consultation. Therapeutic indications for a serious medical condition such as epilepsy, depression, anxiety disorders, etc., that require ongoing monitoring or advice from a doctor are not appropriate for an OTC medicine. Sponsors are expected to follow the relevant EU guidelines and the ICH guideline documents and, of course, the Australian Regulatory Guidelines for OTC Medicines. Links to all of these guidance documents can be found on the TGA website. And that's it for me. I think it's over to Melanie or maybe Steve.

Steven Smith-Fleury

Thank you for that, Kevin. Just bear with me a moment, I just need to get my slides here. We'll just take a brief look now at advertising when it comes to supplying medicinal cannabis products or therapeutic goods in general. Advertising requirements apply to all therapeutic goods, although some medicines such as prescription medicines and biologicals do have requirements that mean they can't be advertised to consumers. It's important to be aware that advertising is considered any promotional material at all. That can include, but not is not limited to, things like medicine labels, including packaging, TV advertisements, websites, including social media sites, and potentially endorsement in social media sites and comments as well. Advertising is regulated by the Therapeutic Goods Act of 1989 and the Therapeutic Goods Regulations of 1990, as well as the Therapeutic Goods Advertising Code.

There are certain circumstances when a good can't be advertised to the public. You can see some of the restrictions here on this slide. These do include, but aren't again limited to, pharmacist-only medicines, except for those that are included in Appendix H of the Poisons Standard. It includes prescription medicines. If we're looking at prescription medicines, of course, we're looking at things that appear in Schedules 4 or 8 of the Poisons Standard, as we discussed earlier. Also prohibited or restricted representations, unless prior approval from the TGA has been granted. Also advertising to health professionals and advertising for health services. We do, on the SME Assist hub of the TGA website, have another handy decision tool. It's called, can I advertise this therapeutic good to the public? It's a decision tool that will help you make that determination. If you are supplying a therapeutic good and you're not too sure about whether or not you can advertise it, jump onto the TGA website. Do have a look at that tool. Go through. It'll ask you a series of questions. And at the end of that, it will provide you some guidance. If you're still unsure at that point, please, again, feel free to give us a call here or drop us an email. We do have contact details at the end of the slides here today. You should all have received a copy of the slides by now. But if you haven't, please don't hesitate to let us know. Just provide your email address and I can get those out to you. Just back to advertising here, while there are advertising restrictions that do apply to therapeutic goods, there might be circumstances in which the advertising of these goods might be permitted. For example, in the interest of public health, as an example of this, in 2019, the TGA did authorise advertisements for vaccines that are or form part of the Commonwealth or state and territory health campaigns. We regulate advertising because, not only can a false claim be misleading to the public, it can also be really unsafe. It's important that we do regulate and monitor advertising of therapeutic goods. The advertising code applies to all therapeutic goods to varying degrees. It does outline key requirements that must be met when advertising to the public. Do make sure that you jump on and familiarise yourself with this piece of legislation and understand what you can and cannot do when it comes to advertising therapeutic goods. That advertising code is available on the advertising hub on the TGA website. Again, if you're having any trouble with it or need any assistance, you can give us a call, drop us an email or you can submit an inquiry through the advertising compliance hub as well. If you do have specific questions relating to advertising, you can also contact the advertising team using the details that we'll provide on a later slide. You can contact them directly. There is the advertising enquiries option on the advertising compliance hub as well. I highly recommend you have a look at that. But again, you can always pick up the phone and give us a call. That brings us to the end of this section. I'm now just going to hand you back to Rachel for some housekeeping before we take a break.

Rachel Wells

Thanks, Steven. It's a lot to get through, isn't it, a lot to take in? I'm just going to go through some basic information that may be of assistance to you. My name is Rachel. I'm from the TGA conferencing and events. I'm also part of the SME Assist team. This is the SME Assist website that Steven had mentioned earlier on and which I believe I provided to you in the link. There is the phone number there. We are actual people behind that 1800 number. Don't be afraid to give that one a call.

Social media slides, are you aware that we're on the Facebook, Twitter, YouTube topic blogs, LinkedIn and Instagram? There's all the information there for those and I will send those out into the chat function a little later as well.

Some other important contact information you might find that you'd like to have close by and handy, we have our TGA info line, our over-the-counter medicine email address, our prescription branch medicines email for application entries and the Office of Drug Control. Advertising team for any of your advertising inquiries and the unapproved products medicinal cannabis email address there.