SME Assist 'Meeting Your Obligations' - Post-market monitoring

Hi my name is Faye Lux and I'm from the SME Assist team at the Therapeutic Goods Administration.

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

Today I will take you through some slides which focus on post-market monitoring. I'll outline what some of your on-going responsibilities are once your product is on the market.

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

This webinar on post-market monitoring is a part of a series of webinars which provide more detail on the regulatory process of therapeutic goods.

Our other webinars focus on:

• market authorisation
• manufacturing, and
• advertising

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

In this webinar, I'm going to provide a general overview of post-market monitoring requirements.

I'll 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 this icon at the bottom, it means that the content relates to all therapeutic goods. That is to say medicines, biologicals and medical devices.

We also have helpful information symbols throughout the presentation that link you to important information on the TGA website. This will be particularly significant for this presentation as many essential details not provided here can be found in the guidance material online.

You can access these links through the PDF version of this document.

Post-market monitoring is the continued upkeep of the therapeutic goods once on they're on the market.

As a sponsor, you are responsible for ensuring your goods remain compliant and maintain an appropriate level of quality and safety. This includes reporting back of any issues with your product to the TGA.

Let's look in general at what you need to report.

We'll start with the occurrence of adverse events which affect all types of products.

The term adverse event, as I've used it here, is broad and encompasses many types of adverse events, such as reactions from a medicine or an injury from a medical device.

Terminology of an adverse event will differ and is important, because it defines:

• what the event is,
• if it's mandatory for you to report and
• how long you have to report it to the TGA.

I will cover these topics in more detail a little later.

For medicines only, we also have deficiencies or defects and medicine shortages. These both have mandatory reporting requirements which I'll outline later.

Let's now go through the basics of an adverse event and how it differs and shares similarities between medicines and medical devices.

Reporting an adverse event to the TGA provides understanding of current issues and helps prevent further issues with therapeutic goods.

There are different pathways and terminologies when reporting an adverse event for medicines and medical devices but the concepts behind them are similar.

For medicines, the term used with capturing adverse events is Pharmacovigilance and reports are received by the the Adverse Event and Medicines Defects Section.

Medical devices term it as part of post-market monitoring, and adverse events reports go to the Devices Post-Market Monitoring Section.

For medicine sponsors, it's mandatory for you to notify the TGA of your Australian pharmacovigilance contact person within 15 calendar days of your first ARTG entry.

We want you to establish and manage a pharmacovigilance system to help collect, record and assess serious adverse reactions and we need to know who to contact in the case of an unexpected event.

You may be subject to pharmacovigilance inspections at any time, which will examine your compliance with the applicable Australian pharmacovigilance legislation and guidelines.

For biologicals, the Biovigilance team is who you report to.

We can request information from you to audit and ensure compliance with any of the products.

Note that this TGA request for information is a legal request under the Act and has strict timeframes that you must adhere to.

For medical devices we perform audits to make sure you are compliant with the essential principles.

Reviews can be done following an adverse event or when we conduct a post market review.

Medical devices do not require you to delegate a particular person for adverse events but request you keep your contact details in TGA Business Services up to date. Consider using a general email, so if someone is away other staff can locate the email.

The Devices Post-Market Monitoring Section may go out on inspections in the future. But at this stage that team currently do not conduct inspections.

Two main concepts are shared when it comes to reporting.

1. Establish a system to identify and collect all reports of incidents, big and small from the reporting person and
2. Keep all of your records.

Medicines, always record four main points of information from the reporter for every report.

And for medical devices, the adverse event reporting form will prompt you to collect more information from the affected user and manufacturer. Best practice here is to collect as much information as possible.

As I mentioned before, terminology of an adverse event is very important. Terminology and mandatory requirements will differ between medicines and medical devices. I'll go through some of these differences now.

The Adverse Event and Medicines Defects section have four main terminologies.

An adverse event which is any untoward medical occurrence in a patient, consumer or clinical investigation, which may not have a causal association with the medicine.

For example, this could be an abnormal laboratory finding.

This does not have the same meaning as a medical device adverse event.

An adverse drug reaction is a noxious or unintended response to a medicine with a reasonable possibility that the medicine caused the adverse event.

A serious adverse drug reaction is much more serious. It's any adverse drug reaction that results in death, is life-threatening, requires or prolongs hospitalisation, results in significant disability or incapacity, or is a congenital abnormality.

A significant safety issue is a new safety issue or validated signal considered by you in relation to your medicine to require the urgent attention of TGA.

An example of this could be finding out that a raw material used in your medicine was suddenly deemed not as safe as first thought.

A serious adverse drug reaction and a serious safety issue are mandatory for you to report to the TGA.

Now let's look at medical device terminology. These have three main categories.

An adverse event for medical devices is an event that led to death, a serious injury or serious deterioration to a patient, user or other person.

A near adverse event is an event that might have led to death or a serious injury.

A serious public health threat or concern is a hazardous event arising from systematic failure of a device, usually coming from an adverse event or near adverse event itself. Typically, it would be something that the TGA must act on swiftly to avoid impact on the public as opposed to an individual's safety.

Medical devices - all of these are mandatory for you to report to the TGA.

Timeframes will vary depending on the type of event.

Timeframes are strict and are in calendar days, so this means that public holidays and weekends are not exempt.

It's important that you read the relevant guidance material to understand the required timeframes.

As an example, significant safety issues for medicines need to be reported within 72 hours and serious public health threats or concerns for medical devices need to be reported within two calendar days.

If you're unsure at any point of the severity of any type of adverse event or drug reaction, report it. Best practice is to treat it as serious and report it right away.

So how do we report?

Reporting pathways for medicines and medical devices differ.

There are three main ways to report a serious adverse reaction, that's through:

• TGA Business Services
• an online form available through the TGA website
• or through email

and significant safety issues are reported through email.

For medical devices, they have an online form available through your TBS account for all reports.

Finally, there are two other mandatory reporting responsibilities for medicines.

A medicine deficiency or defect needs to be reported to TGA.

For example, we expect you to monitor the manufacturer, storage and handling of your medicine and report any deficiencies or defects you find, even if just in a single batch.

The medicine shortages mandatory reporting scheme only applies to prescription and some over-the-counter medicines.

For these medicines, this is a mandatory reporting scheme with timeframes. This allows the TGA to monitor the effects of the shortage, take steps to mitigate its effects and promote awareness of the shortage.

We recommend that medicine sponsors develop internal procedures to ensure they can comply with the mandatory reporting requirements, including the reporting timeframes.

This brings me to my case study. Here we have Daphne and her TENs machine which is a medical device.

And we're going to look at how she reports an adverse event.

So what do you do if someone reports that they have been injured by your medical device?

Daphne has received an email from an affected user, who claims they have hurt themselves using her TENs machine product.

Although Daphne is somewhat skeptical that anyone could harm themselves using her device, ignoring the email is not best practice.

Daphne needs to report this incident to the TGA as an adverse event.

She goes to the TGA website and finds out more information on reporting adverse events for medical devices.

Daphne's first step is to consider what type of adverse event she is dealing with as medical devices have both adverse events and near adverse events.

Both can be associated and by that I mean caused by or partially attributable with the use or the misuse of a device.

An event concerning a medical device also does not have to involve a patient or user. This won't exclude it from being reported.

An adverse event is an incident that resulted in serious injury, illness or death to the patient, healthcare professional or other person.

A 'near' adverse event is similar, except that it could have resulted in serious injury, illness or death.

Daphne is confused and slightly worried.

The complaint doesn't seem very serious to her and she's unsure of where it fits.

Daphne's friend Susie is her go to.

Susie reassures Daphne and tells her if she's unsure about it, she should report it.

The act of reporting is not an admission of manufacturer, sponsor, user or patient liability for the event or its consequences.

An adverse event does not necessarily mean that something is wrong with a product.

And Daphne does not know the extent of the incident. What if it turned out to be quite serious and maybe just that the information provided to her was very vague?

Daphne decides to report it.

Susie then reminds Daphne that there are expected reporting timeframes for adverse events that she'll have to follow.

Together they look at the TGA website, and following the guidelines, determine that they have 30 calendar days to report this incident. She will also have to inform her manufacturer.

The website prompts Daphne to collect information from the affected user.

The bare minimum information she will need to collect are:

• details about herself, as the reporter.
• details about the affected user, referred to as the 'patient'
• details on the product involved
• and details of the incident itself.

So Daphne gets back in contact with the patient and gathers all of this information from him.

Daphne now has to report this information to the TGA.

She's surprised to learn that the online form for reporting is actually done through her TBS account.

Daphne enlists the help of the TGA guidance material on how to submit a report to the Medical Device Incident Reporting system or the MDIR system.

Using this step by step guide, Daphne successfully creates a new report of the incident.

This report is titled the initial report as she does not yet have all the information required to make it a final report.

Daphne receives a Device Incident Report or a DIR number, this is a reference number.

And she'll have to hang onto this DIR reference number, she's going to need it later.

This is not the end of Daphne's adverse event reporting.

Within the initial report, as she is filling it out, Daphne is prompted to seek out more information.

Daphne needs to now check her own information and report this to TGA.

For example, she needs to assess her own Quality Management System, and her own surveillance practices in supplying her TENs machine.

She needs to check that she hasn't received a similar complaint about her device in the past and if the device was returned, Daphne will need to send it to her manufacturer for analysis to include in her final report.

Daphne then needs to log back onto her TBS account and update her initial report, using the DIR number she was given.

After providing the additional information, her initial report then turns into a final report.

She can relax and have a cup of tea.

Once TGA receives the final report, they will typically contact a sponsor within three to four business days.

This is done through email. The email will contain further questions about the report for the sponsor to answer.

For example, we may want to know the current supply numbers of the device, or request a copy of the instructions for use and ask for the sponsor's analysis.

Daphne successfully answers all these questions.

It turns out that the TGA have received numerous similar reports from the improper use of TENs machines.

Although no one had previously struggled with Daphne's device, the TGA held a much bigger picture in view about the machines in general.

And this is why it's so important to report.

TGA informs Daphne that because of a growing number of misuse cases, we will require her to update her instructions for use for the device. After Daphne has completed that, she has successfully reported and addressed the adverse event, fulfilling part of her post-market obligations. This brings me to the end of my case study.

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

Our SME assist pages are designed with beginners to regulation in mind and contain useful tools and guidance articles.

And here are our contact details. We look forward to hearing from you.

Thanks very much for your attention today. I hope that this webinar helps you better understand your Post-market responsibilities.