SME Assist 'Meeting Your Obligations' - Basics of therapeutic goods regulation

Hello, I'm Bronwynne Bulless, Director of SME Assist at the Therapeutic Goods Administration (TGA).

Before we start, I would like to acknowledge the traditional custodians of the land on which I stand today and pay my respects to their Elders past, present and emerging.

Therapeutic goods can be challenging to navigate.

We provide the SME Assist service at TGA to help small and medium enterprises, start-ups, researchers and anyone who is new to regulation to understand their responsibilities.

Please note that these slides are a summary only and should not be taken as law or policy.

The SME Assist team takes complex information on therapeutic goods regulation and makes it easier for you to understand.

We do this through workshops and presentations,

Information on our webpages,

And responding to your enquiries.

We work closely with our expert colleagues at TGA to give you the information you need.

In today's presentation I will provide:

• an overview of our regulations
• and give you some tips and tools on where to go for more information.

This webinar on the basics of therapeutic goods regulation is aimed at beginners.

We have separate webinars with case studies that provide more detail on:

• Market authorisation
• Manufacturing
• Advertising and
• Post-market vigilance.

When it comes to therapeutic goods, lots of people can be involved.

This image represents the different people who might have a role to play:

• the consumer at the top uses the therapeutic good
• we also have the wholesaler, retailer, importer/ exporter and manufacturer
• and also the TGA.

You could be any of the characters circled in yellow and you are also likely to be a consumer at some stage in your life.

All these people have different responsibilities and this presentation helps to clarify what these are.

So first, let's have a look at TGA – who we are and what we do.

We are part of the Australian Government Department of Health. We regulate and monitor all therapeutic goods to make sure that they are safe and they do what they are meant to.

We do this in line with the Therapeutic Goods Act – which provides a uniform, national system of controls over therapeutic goods and this benefits both consumers and industry.

When going through these slides, please look out for the 'i' symbol which will link you to the relevant page on the TGA website. The link here takes you to the Therapeutic Goods Act.

So, what do we mean by a therapeutic good? It's broadly defined as something used for:

• preventing, diagnosing, curing or alleviating a disease, ailment, defect or injury, for example, paracetamol
• influencing, inhibiting or modifying physiology, like a pacemaker
• testing for a disease or ailment, like an MRI machine
• influencing, controlling or preventing conception, such as a condom
• testing for pregnancy, self pregnancy test, and
• replacing or modifying a part of the anatomy, like a prosthesis.

We have decision tools on our SME Assist webpages that help you determine:

• whether your product is a therapeutic good, and
• the classification of your medical device.

Therapeutic goods generally fall under three categories and they are: medicines, biologicals and medical devices

Let's look at medicines first.

• Prescription medicines, like antibiotics, require a doctor's prescription.
• Complementary medicines contain herbs, vitamins, minerals, nutritional supplements, homoeopathic and certain aromatherapy preparations and they include things like: multi-vitamins, some herbal teas and essential oils.
• Over-the-Counter medicines can be purchased without a prescription and are not complementary, things like: lozenges and some cold/flu tablets.
• Medicines also include vaccines, and blood and plasma.

The second category is biologicals which are things that are made from or contain:

• human cells or tissues, or
• live animal cells, tissues or organs.

An example is a skin graft between patients.

And medical devices have a physical or mechanical effect on the body or are used to measure or monitor bodily functions. They include:

• instruments like surgical tools
• appliances like pacemakers
• and materials like sterile bandages.

It's important to know that the TGA doesn't regulate:

• vet medicines
• health professionals
• health insurance
• food standards, and
• cosmetic and chemical standards.

These are regulated by other federal, state or territory bodies.

Note that cosmetics used in surgery such as breast implants and cosmetic injectables are actually regulated by TGA.

It's also worth noting that we sometimes interact with other regulators, so when you work with us, you may also need to work with others.

We don't research and develop new therapeutic goods.

We don't provide clinical advice to individuals.

We don't consider cost effectiveness or recommend one product over another.

And we don't make decisions about subsidies for therapeutic goods.

Here we have an overview of the therapeutic good development lifecycle to show you how the different stages fit together.

First you design and get approval to run your clinical trial.

Then approval to use your unapproved product in the clinical trial.

Then you apply for approval to supply your product which is known as market authorisation.

And possible subsidisation of your product.

Here you can see that TGA is responsible for approving the use of your unapproved product in a clinical trial, and approving the supply of your product, and these are shown in the blue boxes.

TGA isn't responsible for designing clinical trials or subsidising therapeutic goods, which are shown in the green boxes.

Subsidisation is carried out by our colleagues in 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 TGA for market authorisation. However, no pharmaceutical, prosthesis or Medicare listing will occur until the product is included in the Australian Register of Therapeutic Goods. For more information, visit the Pharmaceutical Benefits Scheme website, the Prostheses List Advisory Committee website or the Medical Services Advisory Committee website.

And remember that TGA approval does not automatically mean that your product will be subsidised.

Now let's look at clinical trials in more detail.

The clinical trial environment in Australia is 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 involve the use of 'unapproved' therapeutic goods are also subject to TGA requirements.

While TGA is not heavily involved in clinical trials, our two pathways for accessing unapproved therapeutic goods for experimental purposes are:

• a notification process for lower risk products, and
• an approval process for high risk or novel treatments, such as gene therapy.

Use of unapproved therapeutic goods in clinical trials must be in accordance with:

• national and international guidelines, and
• the relevant protocol approved by the Human Research Ethics Committee.

This table shows various responsibilities under TGA's clinical trials schemes:

The sponsor has overall responsibility for the trial. They make a submission to us, they ensure the trial meets requirements and they're responsible for safety reporting.

The Human Research Ethics Committee assesses, approves and monitors the trial.

The approving authority is the organisation that gives approval for the trial to be conducted at their site.

And the principal investigator personally supervises the trial and complies with requirements, including reporting adverse events.

Our Australian clinical trial handbook provides guidance on requirements when conducting trials using 'unapproved' therapeutic goods.

It helps those involved to understand their roles and responsibilities under our legislation.

For more information on responsibilities outside of TGA requirements, please visit the National Health and Medical Research Council Australian Clinical Trials website.

Let's move on to market authorisation or approval to supply your product. Market authorisation has three stages.

1. In the pre-market step, you compile data and information about your product and include any data you have collected.

   If you have a low risk medicine, like a listed complementary medicine, you don't need to provide clinical data with your application, however, you must hold evidence to back any claims that you make and provide it later, if we ask.

2. In the processing step, you submit your application online and attach the data and information you compiled in the pre-market stage.
3. And if your application is successful, you move to the post-market stage where you have ongoing responsibilities to maintain your market authorisation.

Market authorisation is required before you can supply any therapeutic good in Australia.

And supply is not only the sale of a product. It also includes: exchange, gift, lease, loan, hire or hire purchase.

Things like:

• a free sample
• leasing a dentist drill, and
• hiring out crutches
• all require market authorisation.

So, in summary, if you want to manufacture, import or export therapeutic goods or arrange for any of these, you will need to apply for market authorisation.

And once you've obtained market authorisation, you're known as the sponsor.

The sponsor bears all responsibilities and is financially liable for the therapeutic good.

This is the case even if there are multiple people working on different stages of manufacture in different countries.

And remember, the sponsor has ongoing responsibilities even after approval has been given.

Where possible, TGA makes use of assessments from comparable overseas regulators and international assessment bodies in the regulation of medicines and medical devices.

This can reduce duplication of effort where an assessment has already been conducted outside Australia.

Criteria and processes differ depending on the type of therapeutic good, and note, TGA is still the decision-maker.

There are also expedited pathways available for eligible prescription medicines.

The priority pathway provides a formal mechanism for faster assessment of vital and life-saving prescription medicines.

The provisional approval pathway allows sponsors to apply for time-limited provisional registration of promising new medicines where there is the potential for a substantial benefit to Australian patients.

When market authorisation is granted, the product is added to the Australian Register of Therapeutic Goods or ARTG.

And the ARTG is an online database available on the TGA website where you can search using key words.

It's a good idea to search the ARTG to see similar products that are being supplied.

Each ARTG entry is unique in some way, or 'separate and distinct'.

This uniqueness depends on the type of therapeutic good you have.

Please look at the definition in the legislation that is relevant to your product.

Let's 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, or different dosage or different indications, that product is considered separate and distinct, and will have its own ARTG entry.
• But, if it has a different pack size, so for example a 12 pack of tablets versus a 36 pack of tablets, it isn't considered separate and distinct and a separate ARTG entry is not required.

Sponsorship can happen in lots of different ways and we'll now go through an example of a multiple sponsor scenario.

Here we have a therapeutic good and let's just say it's a prescription medicine.

John from Victoria would like to import this good for supply in Australia, so he applies for and obtains market authorisation through the TGA.

This therapeutic good, in its exact, identical form, can only have one sponsor.

Meanwhile, Anna from Western Australia is interested in supplying the same product. She has two options:

1. She can contact John to see if she can be a wholesaler or retailer of the good and she has to get permission from him. There could be commercial agreements in place, and John is under no obligation to have a commercial arrangement with Anna.

or

2. She can choose to sell the medicine under a different brand name, making the product separate and distinct. In this case, she must apply for market authorisation herself.

When we're assessing your product for market authorisation approval, we use a benefit versus risk approach.

Goods that 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 risks.

Let's look at benefit versus risk in the context of medicines.

Medicines are considered low or high risk depending on:

• the claims made about the medicine
• what it contains, and
• the benefits and risks associated with using it.

In Australia, lower and higher risk medicines are given particular names:

• lower risk medicines are called Listed Medicines
• higher risk medicines are called Registered Medicines
• the ones in between are called Assessed Listed.

The take home message here is that higher risk, registered medicines require more rigorous pre-market evaluation.

As this table shows:

• no prescription medicines are listed
• some over the counter medicines are listed, and
• most complementary medicines are listed.

Conversely:

• all prescription medicines are registered
• most over the counter medicines are registered, and
• some complementary medicines are registered, for example, some folic acid tablets and some head lice products.

In general, if you have a prescription or over the counter medicine, you'll need to go through a more rigorous process.

On the other hand, if you have a complementary medicine, it's generally less tightly regulated.

Similarly, medical devices are classified according to their intended purpose and the level of harm they may pose to users or patients.

Classification takes a number of factors into account, including:

• the degree of invasiveness in the human body
• the duration and location of use, and
• whether the device relies on a source of energy other than the body or gravity.

As shown in this table, each class has a particular risk associated with it:

• so Class I devices such as tongue depressors are low risk, and
• Class III devices such as heart valves are high risk.

Our work continues over the lifetime of every therapeutic good, from manufacturing through to adverse events.

Our regulatory compliance functions 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 promote high levels of voluntary compliance through engagement and education.

I'll now take you through some general terms and concepts.

All the different types of therapeutic goods have their own Guidelines which are updated regularly.

These Guidelines help with finding out what you need to do when applying for market authorisation and complying with TGA requirements.

Note they are guidance only and the relevant part of the legislation is the definitive source of information.

The Australian Regulatory Guidelines are located under the 'Industry' tab on the TGA website.

The different types of therapeutic goods are listed underneath, just select Standards and guidelines and you'll find the relevant Guidelines there.

You can also receive regular updates of new guidance material such as:

• cyber security for medical devices, and
• comparable overseas regulators.

You can find the TGA Business Services Portal under the 'About the TGA' tab.

This is where you submit and manage your applications and every sponsor needs to have an account.

Fees and charges are also under the 'About the TGA' tab.

We recover 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 are an annual tax.

All therapeutic goods on the ARTG are subject to annual charges, except export only products and products that fall under the Annual Charge Exemption scheme.

We encourage you to look at the link to fees and charges so you know what to expect.

The Annual Charge Exemption or ACE scheme allows for exemption of annual charges until a product first generates turnover.

All new entries on the ARTG are eligible.

Sponsors need to make a declaration each year confirming $0 turnover.

Note that fees are not included in the ACE scheme, only charges.

This is how you access SME Assist, on the front page of the TGA website.

And here are our contact details.

We look forward to hearing from you.

Thanks for listening and I hope that this webinar on the basics of therapeutic goods regulation helps you to understand the regulatory process.