Presentation: NATA TGA IVD information session 1 - Refresher: Regulatory framework for in-house IVDs

Andrew Griffin
Afternoon, everyone.
And it's about 12:30.
We’ve still got a lot of people coming in, so we might just wait a couple of minutes before we start.
OK, at 12:31 might make a start.
So welcome everyone to the first of our sessions to be run in conjunction with TGA and today we have Shraddha Swami speaking today director of devices in IVD Diagnostics section.
We're really thankful to Shraddha, Rebecca and Euan for volunteering to talk to us about the IVD framework as it exists in Australia. It's obviously generated a lot of interest. We have over 400 people registered for today. So yeah, that's very exciting, we have so many. 

The sessions will be run as a series, so each one being different, not repeated, so we hope you can attend all three sessions over the next today, Thursday and the following next Tuesday.
In terms of, as there are so many participants in this meeting, we won't take questions today live. We have just too many people to be able to manage that.
So what we'll do is provide email addresses at the end for you to send your questions in and we'll probably answer them in a sort of frequently asked questions type document that will be published.
As we liaise who's the best organization to answer those questions, whether it's TGA or NATA. I would say, if you have specific questions about your laboratory and your in-house IVD then probably speak to your client coordinator first because that's more of an accreditation NATA type question. So speak to your client coordinator 

If you're not accredited yet or you're technical assessor and you have questions then use the NATA email address we will be providing to you at the end.
And just to note that these sessions are recorded.
You'll note when you joined it says session recorded.
So what we will do is endeavour to post those probably on the TGA website when all three are completed with post those on the TGA website and we'll provide a link to you where you can find those on the NATA website and also on our socials.
So I think we'll hand over now to Shraddha to begin the first presentation of today.
So I hope you'll enjoy it and once again, thank you all for attending.
I see we are over nearly 150 people already.
So Shraddha, I might pass over to you, take myself off screen.

SWAMI, Shraddha
Thank you.
Thank you, Andrew, and good afternoon everyone.
And just a couple of logistic checks, you can hear me alright.
You can see my screen in the slide show mode.
Just a thumbs up would be great.

Andrew Griffin 
Yes.

SWAMI, Shraddha 
Awesome.
Thank you.
Well, good afternoon, everyone, and welcome to the first of the three information sessions on the in-house IVD regulatory framework.
Andrew has already given my introduction.
I'm Shraddha Swami, I’m the director of the devices in vitro diagnostics section over at the TGA and will be taking you through the session for refresher on regulatory framework on in-house IVDs.
Before we begin, I would like to acknowledge the traditional owners and custodians of the lands on which we meet today and pay my respects to elders, past and present.
I would also like to extend that acknowledgement and respect to any Aboriginal, Aboriginal and Torres Strait Islander peoples here today.
The aim of today's session is to cover definitions in our regulations, the legislation and regulatory requirements underpinning our framework, clarify the role of TGA in NATA and the testing laboratories in ensuring the in-house IVDs being used, are safe and perform as intended and some common compliance issues we have identified and also the intention is to inform you about some of the work that is currently in progress in the in-house IVD space.
This, what you can see on the screen is the definition in our regulations of what is defined as an IVD medical device.
I'm not going to go through it, but basically an IVD medical device is defined as a device that is intended to be used for in vitro examination of sample taken from the human body and is intended to provide therapeutic information.
Those intended for general lab use, say such as pipettes, and that are not presented for use as an IVD, are not IVD medical devices.
I guess the important point here is what the manufacturer claims as the intended use of the device and that will be used to determine whether the device is an IVD medical device or not.
This slide covers basically wanted to indicate what is in and what is not an in House IVD. In-house IVDs are pathological tests that have been developed or modified within a laboratory or a laboratory network to carry out testing on human samples where the results are intended to assist in clinical diagnosis or they are used in making decisions concerning clinical management.
In House IVDs are where a laboratory or the network is responsible for the design and production of the in-house IVD, and that includes design, control through assignment of specification, assembly, processing and packaging of components that make it an in-house IVD, or assigning the intended purpose through the information supplied along with the IVD, and this could be through use of laboratory controlled documents. IYDs developed in-house but supplied outside of the laboratory or the network fall outside the scope of the definition of in-house. And in-house tests that are developed by the Laboratory for research purposes only, that is where there is no reporting of patient or client results, are not IVDs.
Now one of the examples for in-house IVD is where you using a commercial IVD, say which is approved for use with a saliva sample type and you're using it with a different specimen type, so you're using it with a nasal specimen type which is not specified in the manufacturer’s instructions for use. Then that particular device where you're using a commercial IVD with a different sample type not specified in the manufacturer's IFU, becomes an in-house IVD.
We've also defined in our regulations on what a laboratory network is.
So laboratory network’s basically are a group of organisations that operate under a single quality management system.
Slide provides information on the authority to regulate, where the authority to regulate IV's in Australia is covered under, so it is basically covered under the Therapeutic Goods Act and the Therapeutic Goods Medical Device Regulation.
These pieces of legislation includes the authority, the provisions and the regulatory requirements for in house IVDs supplied or available for use in Australia.
Now, so as a blanket rule, all therapeutic goods must be included in the Australian Register of Therapeutic Goods before they can be legally supplied in Australia, unless exempt. Now this slide, I just wanted to cover a few things that, a few provisions which are available in our regulations that enable this or provide us with this ability to exempt. Now in-house, just before we go into the exemption, in house tests or IVD's are considered to be supplied when they are used to test the patient specimen and report the results for patient management or clinical decision.
Now the various types of exemptions or the provisions for various types of exemptions that are available in our regulations include the experimental purposes one.
So the laboratories that need access to an unapproved commercially supplied IVD or where they develop an in-house IVD specifically for experimental purposes, those are exempted. Now the emergency exemption, this emergency exemption allows certain therapeutic goods to be made available in Australia usually in circumstances where it is urgent without including in the ARTG and usually it is to deal with actual emergencies.
This was basically one of the provisions that was used during the initial COVID pandemic management phase to make the tests available, and this is an exemption that can typically be initiated by government only.
Now the other one which is relevant to the, very much relevant to the in House IVD space, is the exemptions with conditions.
Now the class one to three in-house IVD's and certain class 4 in-house IVD's which the class 4 in house IVD's typically those are used for donor screening purposes, are exempt from inclusion in the ARTG. The important point to note here is they are exempt from inclusion in the register, but they are associated with certain conditions which I will go through in detail in in my next few slides.
The other aspect is the special access scheme or the authorized prescriber scheme.
Now these exemption is typically where the health practitioners can apply to access unapproved products to either use it for individual patients on a case by case basis through the special access scheme and the authorized prescriber scheme is usually for multiple patients with the same conditions, so that qualifies for an approval under an authorised prescriber scheme.
Now, if you're unsure about whether the device that you have is exempted on or not, please contact us and we will be able to provide you with the information of whether it's exempt or not.
Now in terms of authorised prescriber scheme and the Special access scheme, if you intend to seek approval, there is information on our website for you, you need to apply to get this approval and there is information on our website on what the different, what is the avenue to make such an application and what is the sort of information that needs to accompany such an application.
Now, the overview of IVD regulation, as you're already aware IVD framework was introduced in 2010 with IVD's being regulated as a subset of medical devices. In Australia, we have a single framework that covers both IVD's and medical devices.
Unlike some other jurisdiction like Europe, for example, that have separate regulations for medical devices and IVD medical devices. Now in that for IVD's, this particular framework applies to both In-house IVDs as well as commercial IVDs. The risk based classification is the same for commercial and in house as it does not matter whether the device is in house or commercial, the risk posed to the patient is the same.
The regulatory oversight by TGA for in-house IVD's the first two, the commercial, as it is managed with support from accreditation bodies such as NATA and the performance requirements are determined under the and NPAAC standards.
The classification of IVD's, the IVD's are classified based on the intended purpose and the risk an incorrect result would pose both to the individual health as well as the public health.
Now there are few examples in the table there, but basically tests that are used to detect high risk transmissible agents such as HIV and those kits used for the purposes of donor screening are classified as Class 4 purely due to the high personal risk and high public health risk due to the transmission and the impact.
Whereas test like pregnancy, ovulation test kits are classified as Class 2 due to the medium personal health and the low public Health Risk. Classification is determined based on the intended purpose of the device, the laboratory or the manufacturer is responsible for determining the classification based on the intended purpose and the classification rules that are prescribed in our regulations.
Now, what does the laboratory need to do?
A laboratory manufacturer, manufacturing or developing an in-house IVD, must determine whether the device, I think the first step is you must determine whether the device fits the definition of an in-house IVD.
Once you've determined that, the next important part is the classification of the device, that classification needs to be determined by the intended purpose and the classification rules that are described in our regulations.
Once the class is determined, the laboratories or the manufacturer need to understand and comply with the applicable conformity assessment procedures, the level of technical documentation and the regulatory obligations. Classification is important because as that is responsible or that directs the requirements that go along with the classification of that type.
I will go through in my next few slides. Basically, what I mean when we say conformity assessment procedures, technical documentation and what are the regulatory obligations that we are referring to in the in-house space.
Conformity assessment procedures. So conformity assessment is the systematic and ongoing examination of evidence and procedures to ensure that a medical device complies with the essential principles.
What it usually relates to it relates to the quality management system requirements for developing the in-house IVDs. It can include specific regulatory requirements, such as the post market monitoring requirements. It could refer to specific record keeping requirements and also the obligation of making or providing information to the TGA when requested.
So all of this I guess conforms to what is called, referred to as conformity assessment procedures.
So the conformity assessment procedures. There are two types of conformity assessment procedures that apply in the in-house IVD space.
One is which applies to class one to three in-house IVD's and the other is for the class 4 in-house IVD.
So in the class one to three in house IVD's, the laboratories need to seek and maintain accreditation by national accreditation bodies such as the NATA, against the ISO 15189 requirements and the performance requirements detailed in the NPAAC standard.
This also includes the requirement to establish and maintain a post market monitoring system, which is for, which basically requires monitoring and reporting in relation to post production phase of the device or the performance of the device when it is in use.
The other important regulatory requirement is the notification to TGA.
Now if it is in the financial year, notification to TGA for these one to three in House IV's is a regulatory requirement.
If it is in, if the device has been manufactured in the financial year, a Class 1 to one to three in-house IVD's, and it is not covered by the previous notification that you've provided to the TGA, then you are required to notify by 1st of July of the next financial year or 20 working days after manufacturing the device for the first time.
So all of these sum up the requirements for the laboratories who are responsible or who have manufactured class one to three in-house IVD's.
The conformity assessment procedures for the class 4 in-house IVDs. These are these requirements are quite similar to the class for Commercial IVD's and this is because of the risk these IVDs posed to the public health and the personal health.
The these class 4 in house invites need to be included in the ARTG unless they're exempt.
Now I'll touch on the exempted part, but this slide will basically cover how can you include the device in the ARTG, how can you meet this requirement?
There are basically two ways. One way, first pathway one is a two-step process come to the TGA where you're where you're applying to the TGA to seek a conformity assessment certificate.
This requires the manufacturer or the testing laboratories to apply to the TGA for a TGA Conformity Assessment certificate.
Now, once you make an application, TGA will undertake an onsite inspection to assess the QMS requirements and they will undertake also a desktop audit or an desktop assessment of all of the technical documentation and to ensure that they comply with the conformity assessment procedures and the essential principles.
Once the compliance has been demonstrated, a TGA Conformity assessment certificate will be issued. That's the first step of obtaining a certification.
Now the second step is where the manufacturer will provide the TGA Conformity Assessment Certificate to apply or will use the TGA Conformity Assessment Certificate as an evidence to apply for the ARTG inclusion application.
Usually, if it is supported by a TGA Conformity assessment certificate, there will not be any assessment as TGA has already looked at the technical documentation and the device will be included in the ARTG. The sponsor will be notified once the device is being included along with the ongoing obligations the sponsor will need to have while the device is included in the register.
Fees will be applicable for both of the steps, to obtain the TGA Conformity Assessment Certificate, as well as for the ARTG inclusion application, and when next further slides will cover what those fees are as well. But this is just to give you an idea of what that pathway one is.
Now the pathway 2 which is in the slide is where laboratory has a NATA Accreditation or has a TGA GMP license. Then what they can do is they don't have to apply for the TGA Conformity Assessment certificate.
They can apply directly for ARTG inclusion now as part of that inclusion, application TGA will undertake a desktop assessment, which we refer to as a mandatory application audit, which is basically a desktop assessment to go through all of the technical documentation to ensure that they, to verify whether they have demonstrated compliance with the relevant essential principles and delegated decision will be made whether to include or not to include the device in the ARTG. In this pathway two, there will be only one set of fees that will be applicable, which is for the application of ARTG inclusion.
Now, I've been referring to this essential principles, so essential principles are basically the safety and performance requirements that are detailed in our regulations.
So all devices irrespective of what classification they are, are required to have technical documentation to demonstrate they comply with the safety and performance requirements.
Higher the classification, the depth of information required in a technical documentation will differ, class four more requirements compared to a Class 3 or Class 2 device IVD, which will be a lesser depth of information required. Now in-house IVD's are required to comply with the essential principles as part of the exemption that they currently have.
The compliance with the NPAAC standard is considered currently as compliance with the relevant essential principles for safety and performance of an IVD medical device.
Now, once the device is in use, it is very important that there are systems.
Let me rephrase it.
I guess before you notify or before the device is being supplied for use, it is important that you have a post market monitor monitoring system in place.
Then, once the device is in use, these systems are required to monitor the ongoing performance of the device, such as through, it could be through participation in the External quality assurance programs and also the requirement to report any adverse events to the TGA and you also have to notify the TGA of any malfunction or deterioration of an in-house IVD that has led the laboratory to take steps to cease using the device. So the post market requirement as much as it is important for you to have validation documentation available before, and as much as it's important to undertake validation, have the documentation available before you supply the device, it is equally important to have a post market monitoring system in place once the device is in use, so you can ensure and monitor the ongoing performance of the device.
Now this is there's some of the regulatory exemptions that are specific to in-house IVD's. So I think we've gone through the class one to three in-house IVD, the exemption that they currently have that is they're not required to be included in the ARTG.
The important aspect is yes, they are exempted, but they are exempted with conditions. What are those conditions? They must comply with the essential principles, they must comply with the applicable conformity assessment procedures, which I've gone through with you in the previous slides, and they need to make information available to the TGA when requested. TGA under the regulation, has the authority to request the laboratories or the manufacturers for information regarding the in house IVD medical devices and the manufacturer are required to provide that information to the TGA and that information could pertain to the safety and performance requirements of the relevant IVDs.
Now, the class 4 in house IVDs. These are not they do not have a blanket rule of exemption, like all class 4 in-house IVD are not exempted. There are certain class 4 in house IVD's where there are there is currently an exemption in place and that is for the class 4 in-house IVD's used for screening of samples from potential donors for use in faecal microbiota transplant manufacture. All the exempted these also come with a set of conditions. They need, the laboratories need to make need to ensure that they have data to demonstrate the safety and performance requirements, they need to notify, the laboratories are required to notify TGA no later than 20 days after the manufacturer such a test and ensure that they obviously have data to demonstrate its performance.
TGA can ask for this information and the labs must be able to provide this information if requested. So I guess the summary of the slide is yes, they're exempted, but they're exempted with these conditions and the laboratories must ensure that they meet these conditions that the exemption is associated with.
Now in this slide, I just wanted to briefly go through and the IVD inclusion process because this process is still applicable for laboratories that manufacture class four in-house IVDs.
This is a very high level simplified flow chart of the different steps involved, so the different steps are TGA will, as a laboratory if you want to include a class 4 in-house IVD in the ARTG you need to make an application to the TGA with the information on the device, the manufacturer and the sponsor details. There is an application form on our portal. You need to make that application and it will require you to pay an application fee which needs to be paid and then an application becomes effective and it comes into the our portal.
So once an application is received by the TGA, we undertake a preliminary assessment to ensure the device classification, the GMDN code and all of that are appropriate.
We will advise the sponsor of an application audit. Now as these devices are class four, they undergo mandatory application audit, so we will advise the sponsor of the application audit and also request technical documentation to be provided along with the application audit fees invoice. Typically 20 days are provided for the sponsor to provide us with this information. Once the application audit fees has been paid and the information has been submitted, TGA undertakes desktop assessment and can and during this process of desktop assessment, it can request laboratories or the manufacturer for additional information as required during the audit process.
Once the audit has been completed, a delegated decision is undertaken to either include or not to include the device in the register.
There is no on-site inspection by the TGA as part of this application audit. It usually comprises of desktop audits only. For example, I just give you a bit of a very high level idea on what this application audit actually means. Say if an in-house IVD is developed and is the same class as the, if an in-house IVD is developed by modifying a commercial IVD and is the same class as commercial IVD and the only change say is the expanded indications of use. The application audit in that instance will only focus on the expanded aspect and the fees will be reflective of the assessment effort.
So that's just to give you an idea of the what the desktop application audit usually covers.
Now the inclusion in the ARTG the up, the relevant fees that would be applicable.
The application fees, which is $1098 for in in this in the in House framework space it will be the fees for class 4 in House IVD's and the audit assessment fees which will be which is around 22 grand. The one point to note on the application audit fees, TGA has recently completed a public consultation on the fees proposal to further reduce the application audit fees. Now, if the government agrees with this proposal and the fees will be further reduced to around 14K, to around 14,000 is what I understand the proposal is and those if the government agrees, those new fees will be implemented from the next financial year, which is the 24/25 financial year, but this is obviously subject to government approval.
The other point to note is once the device is been included in the ARTG, unlike the other commercial IVD, there is no annual charge for class 4 in-house ARTG entries.
So there is no ongoing maintenance fees that they that is applicable to the class 4 in house IVD's.
I guess with that, uh, this is more a, I guess, a 1 page snapshot of what the regulatory requirements are based on the classification of the device.
Now this is basically to detail what the, or clarify, I guess, what the role of TGA is when it comes to in House IVD, so our regulatory requirements indicate that you need to notify TGA. Once you've notified to us TGA and looks records this information in an in-house IVD notification database and basically it helps us or provides us with the visibility on the in House IVD's supplied for use and if there is any information that we need or any information that we need with respect to those in House IVD's that have been notified to us, we have the authority to reach out to the relevant labs. TGA is responsible for the inclusion process, inclusion assessment, assessment and inclusion of class 4 in-house IVD in the Australian Register of Therapeutic Goods and also responsible for the different exemptions that are in place for the in House IVD's.
We assist NATA with information on In-house IVDs and also with technical assessment for complex technologies, as requested by NATA and obviously from, by consent from the labs, TGA's role is to ensure regulatory oversight for in House IVD used the safety and performance of the IVD but not the clinical or the laboratory practice.
Now the different interactions with the NATA that I indicated, where is all of this detailed or what provides us with that authority to do so? It is the MOU with NATA that provides us with this authority, which is covered in my next slide.
So we do have an MOU with NATA. It is available on the website if you would want to have a look at it. Basically, it sets, clearly sets out the roles and responsibilities of NATA and the TGA. It sets out the roles and responsibilities it for the TGA, it allows information sharing between the TGA and NATA. It allows us to provide technical assessors for participation in the laboratory accreditation or desktop audits to undertake assessment for complex technologies and also liaise with NATA on any adverse event related information with respect to the in House IVDs.
Now I did want to take this opportunity to also highlight some of the compliance issues that we have identified and some of them are, we have not received adverse events notification on in-house IVD's. Potentially this may be due to the lack of awareness of the post market reporting requirements or also lack of awareness on actually, what qualifies for an adverse event.
Our regulations as well as the In-house TGA guidance available on our website provides information on what qualifies for an adverse events.
We are also currently in the process of updating the in-house IVD guidance and the intention is to provide a bit more information and a bit more clarity on the post market requirements and it would be good for the labs to familiarize with this so that you understand the regulatory obligations. And in my previous slides I did indicate that the class four in house IVD 's are exempted but they are exempted with conditions meaning they are required to notify us, they are required to comply with the conditions and one of the conditions is to notify that they're Undertaking such testings. there has been a lack of notification that the TGA has seen, so it's important for the labs to understand this requirement as well as comply with this requirement. Certain other issues That we have identified, such as the investigational use only device, you know being used for the purposes of reporting results or for the purposes of clinical and patient management. So I guess that's also some of the things that we have tried to, we are trying to make it more clearer in our guidance to say that these such devices cannot be used for the purposes of the supply and it should not be used for the purposes of patient clinical decision making.
What is coming or what we are currently working on? the new in House IVD notification form, session three of the series will cover the new form.
It will also be accompanied with an update to the in-house IVD guidance, which will aim to provide greater, which will aim to provide a lot more clarity on the regulatory requirements and also provide information on this new form, the intent and also guidance around how to complete the new form. in the companion diagnostics space, the companion diagnostic guidance has been updated to provide clarity on how to determine whether the device is a companion diagnostics or not.
The clinical and performance requirement and also the associated clinical and performance requirements.
This, we are in the current process of currently releasing this shortly for public consultation, so please watch this space in and on the TGA website. 

Along with the public consultation of the on the companion diagnostic guidance, we will be publishing the TGA CDX list. initially this will include the list of only the commercially developed companion diagnostics But the intention is as we move ahead in the next tranche or so, to include the list of in House IVD companion diagnostics as well.
So that's really what's happening in the in-house IVD regulatory framework space.
And we come to the end of the session and I do hope that it has provided you with a, I guess, a refresher on the regulation. I'm more than happy to receive any questions you may have to either of this inboxes and we will aim to get back to you.
Any responses received through the inboxes, we will aim to get back to you with responses before your next session this Thursday, which is on the data requirements and assessment approach, including companion diagnostics.
With that, I would also like to thank NATA for facilitating this and to you all for attending these sessions as well.
Hope you found it useful and would also want to conclude by saying that if in doubt about the device classification, the regulatory side of things, the existing exemptions in place, please feel free to contact us on the IVD inbox and we are very happy to provide any assistance as needed.
Thank you.

Andrew Griffin 
Thank you, Shraddha. That was that was really good. And it's really interesting there.
Some things that I didn't know. So and I've been doing this a long time, so I've got some questions for you but and so thank you everyone for attending today the email address again is NATATGAIVD@nata.com.au.
That's the preferred email looks a bit weird on screen, but it actually makes sense when you read it out and so it Thursday same time 12.30.
And I think Rebecca Corey is presenting on Thursday.
So once again, thank you for attending Shraddha.
Thank you for your time.
It was really thorough and comprehensive, so thank you.
I'm sure we get lots of questions and thank you everyone.
We'll see you on Thursday.

SWAMI, Shraddha
Thank you everyone.