SME Assist 'Meeting Your Obligations' - Manufacturing

Hello and welcome. I'm Melanie Leake from SME Assist at the Therapeutic Goods Administration.

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

I'm going to take you through some slides which focus on manufacturing to help you understand more about these requirements.

These slides are a summary only and should not be taken as statements of law or policy.

This webinar on manufacturing is part of a series of webinars which provide more detail on the regulatory process for therapeutic goods.

Our other webinars focus on:

• market authorisation
• advertising, and
• post-market monitoring

These can all be found on the TGA website and will help you navigate the regulatory maze.

Let's take a look at a general overview of manufacturing requirements.

I will be covering therapeutic goods in general.

Look out for these icons on the slides.

• The icon on the left represents medicines and biologicals. So when you see this icon, the information on the slide relates to both medicines and biologicals
• The icon on the right represents medical devices
• And if you see the icon at the bottom, it means the content relates to all therapeutic goods, being medicines, biologicals and medical devices.

We also have helpful information symbols in the PDF version of this presentation that link you to important information on the website.

So what do we mean when we refer to manufacturing?

It's any stage in the production of the good and depends on the type of product, but can include the following steps:

• producing
• processing
• refurbishing
• assembling
• packaging
• labelling
• testing and
• release for supply

There are certain regulatory requirements that must be met when it comes to manufacturing and we assess the manufacturing processes to make sure that they meet certain standards.

The standard for assessing medicines and biologicals is called Good Manufacturing Practice or GMP.

The assessment process for medical devices is called Conformity Assessment.

Both of these have guidelines and criteria that need to be met to demonstrate compliance.

For medicines and biologicals that contain live animal cells, tissues or organs, the criteria is the PIC/S guide to GMP. PIC/S stands for pharmaceutical inspection scheme or Pharmaceutical Inspection Convention & Pharmaceutical Inspection Co-operation Scheme.

For biologicals that are derived from human cells, tissues or blood products, it's the Australian Code of Good Manufacturing Practice for human blood and blood components, human tissues and human cellular therapy products.

For medical devices, the set of criteria for assessing manufacturing is called the Essential Principles.

Manufacturers that meet standards are issued with a certification, this is the manufacturing evidence that you need to present in your application.

If your manufacturer is located in Australia, they need to obtain a GMP licence from TGA.

They have to submit a GMP application to us with details about their manufacturing site.

This may also involve an on-site inspection.

After the inspection, the manufacturer then forwards the details of their GMP licence to the sponsor.

The sponsor is considered responsible for ensuring their manufacturer has a GMP licence.

If your manufacturer is located overseas, it's the sponsor's responsibility to make sure their manufacturer has GMP clearance as opposed to a GMP licence.

The sponsor submits this manufacturer evidence as part of their market authorisation application.

For medical devices if a manufacturer can demonstrate that they meet the relevant Essential Principles, they are issued a certificate or declaration of conformity.

Note the manufacturer evidence does not need to be submitted as part of an application for a Class I or export-only device. But it must be available upon request after inclusion in the Australian Register of Therapeutic Goods.

For other device types, the sponsor has to submit the manufacture evidence through TGA Business Services and get approval before submitting a market authorisation application.

The sequence of events is slightly different for medicines and biologicals compared to devices.

For medicines and biologicals, the manufacturer evidence is submitted with the market authorisation application.

For devices, you submit your manufacturer evidence first, pay the fee, get approval and then submit your market authorisation application.

We have the 'Good manufacturing practice application decision tree' that can help you determine what type of GMP application may be required.

If your manufacturer is located overseas, you have a few options to obtain GMP clearance or a declaration of conformity.

We have various international agreements and arrangements with other countries.

For medicines and biologicals, these are called mutual recognition agreements or MRA's.

There are around 25 different countries that are part of these agreements, including United States, Canada, Singapore, United Kingdom and numerous European countries.

If your manufacturing site is not one of these countries or you're not eligible for MRA, you have to obtain GMP certification through TGA which may involve an on-site inspection by one of our GMP inspectors.

It's similar for devices, we have comparable overseas regulators which include all of these countries and regulatory authorities.

In essence, we accept manufacturing certification by us and we accept certification from other countries which are a part of all these agreements.

We regularly inspect manufacturers of therapeutic goods to ensure compliance.

Inspections can happen at any stage during the market authorisation process: from pre-market through to post-market.

Generally:

• we'll contact the manufacturer informing them that an inspection will be carried out and agree on an inspection date
• the inspection might take a day or two
• the inspector identifies any deficiencies
• the manufacturer has to address the deficiencies and provide a response detailing any corrective or preventative actions

The manufacturer must agree to have their site inspected if required.

It's the sponsor's responsibility to have an inspection agreement in place with the manufacturer.

For our case study, we have Susie.

She wants to be the sponsor of a prescription medicine that is manufactured in Portugal.

Because the manufacturer is based overseas, Susie is responsible for obtaining GMP clearance.

Susie's first step is to confirm the following details with her manufacturer.

• Whether the product is regulated as a medicine in Portugal - Susie confirms it is
• Whether the site has been recently inspected by the Portuguese regulator - Susie confirms that it has
• Whether the manufacturer has a GMP equivalent certificate to TGA standards - yes they do and they forward this onto Susie

Susie uses the GMP clearance application assistance tool to check the general evidence requirements for her GMP application.

The tool guides her to find out a few more details about her product.

She needs to check the Mutual Recognition Agreement list of countries.

If a country is not listed, then you can't use that pathway.

Mutual recognition is the most straightforward pathway, but you may be able to use other pathways.

The tool also asks Susie to check if her type of product can be issued GMP clearance.

GMP clearance can be issued for manufacturers of:

• non-sterile active pharmaceutical ingredients or APIs
• non-sterile finished products
• sterile or biotech APIs
• sterile or biotech finished products and
• contract testing laboratories

She sees that she can get GMP clearance for non-sterile products, such as her tablets.

There are three possible options for GMP clearance.

The first is the Mutual Recognition Agreement 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 is the compliance verification pathway which you could use if:

• the manufacturer doesn't meet the criteria for MRA and;
• the site has been inspected by an MRA regulatory authority

The third is the GMP certification pathway, which you could use if:

• the MRA or CV pathways are not applicable or
• no acceptable evidence from a recognised regulatory authority is currently available. For example, if you require a GMP certificate for your sunscreen which may not be classed as a medicine in another country

In Susie's case, she can proceed down the MRA pathway because:

• she confirms that Portugal is an MRA country
• her product is regulated as a medicine in Portugal
• the site has recently been inspected by Portugal's regulatory authority and to TGA standards

Note that if Susie's site hadn't been inspected by Portugal's regulatory authority, she would not be able to pick option three involving a TGA inspection.

This is because we have a mutual recognition agreement with Portugal and we would ask their regulatory authority to perform an inspection on our behalf.

We would only perform the inspection if the product was not regulated as a therapeutic good in Portugal.

To proceed down the MRA pathway, the overseas regulator must:

• meet TGA standards for GMP codes and;
• have recently inspected the manufacturing site to TGA standards

Evidence must be current, accurate, complete and translated to English if necessary.

Susie submits her GMP clearance application through TGA Business Services by:

• logging in and selecting 'Clearance Application'
• providing the required details
• paying the associated fee, and
• agreeing to the declaration

Susie has now submitted her GMP clearance application.

Please visit the SME Assist hub on the TGA website which you can find under the heading 'Industry'.

Here you will find guidance articles and decision tools for beginners on various topics including 'what type of GMP application do I require?'.

Here are our contact details and we look forward to hearing from you.