Audio automatically transcribed from the webinar. Please excuse any minor spelling and grammar mistakes.
[00:00:00] Kelly Stanton: Combination products, regulatory approach, and GMP requirements, quick disclaimer. These this presentation represents personal opinions and interpretations does not reflect any company or organizational position. And a lot of the material we've taken today is sourced from various PDF, sorry, FDA presentations, and other communications available to you in the public forum.
Our topics to. Introduction to combination product CGMP requirements, the classification of drug device, combination products and CGMP requirements best approach for development of these types of products. Along with a few pitfalls here and there that we've seen in our experience in industry Risk management and control strategies, the new regulations applying for these products between the FDA guidances, as well as some of the new guidances and things coming out in European Canadian markets, for example.
And then we'll talk a little bit about labeling again, reminder please do post questions in the Q and a box. And we'll either try to grab them as we go along or we will answer them at the end. Combination product GMPs. What does this look like? We should start by talking about what is a combination product so that we can make sure we're all on the same page from an applicability perspective.
So it is defined as a product comprised of two or more types of medical products. So this could be drug and device, a drug of the biologic or all three of these things together. The intent or the the intended use of this product is based on the capabilities of two or more different product types to provide effective health care.
It's important to note that the drugs and devices are still covered by the relevant individual regulations. So drugs are covered under 2 10, 2 11. The medical devices are covered under CFR eight 20 or again, other markets outside the U S you would have the relevant regulations from both sides of the fence.
And the constituent parts are how the regulations refer to the individual components that put together comprise the combination product. For purposes of this. Presentation. We are talking about the combination of a drug and a device, a drug, and the biologic, a device, and a biologic, or all three of those things together.
We are not today talking about combinations of multiple drugs together or multiple devices in use together those things while could be called, a combination type products. Those are not in the scope of the regulations that we're looking at today.
So classification of these things and how that falls into the GMP framework.
It's important to note that the articles and combination products retain their regulatory status as a drug, a device, a biologic, or a cell and tissue based products. The finished combination products are subject to the CGMP requirements that are applicable to each constituent parts. So as we talked about in the last section, The the device is regulated under eight 20 or the G QSRs.
And the drug is regulated under 2 10, 2 11. Combination products were subject to these requirements before 21 CFR part four came into effect. And all of these things have to be considered together. When you talk about regulations, submission procedures, pathway to market. And post-market safety requirements in most markets.
So lots of applicable GMPs again, it gets pretty complex, but if you've got a good handle on the requirements for each constituent, you can then figure it out. What parts apply? So cross labeled products, for example constituent parts are sold separately. But perhaps those things are sold together.
So things like light emitting devices, light activated drugs, certain imaging devices and imaging agents. For example, the drug is not used by itself. It's used for the purposes of a scanning procedure that would be cross labeled. Cool packaged are where the constituent parts are packaged together.
So first aid surgical kits or syringes, pre-packaged with the drugs already inside as opposed to sold separately or they're packaged together to be sold as a kit. And then you also have single entity where a chemically or physically combined constituent parts, such as drug eluting, stents, prefilled, syringes, transdermal patches, et cetera, et cetera.
Those things must comply to both drug and device. But there are ways to streamline. You don't have to have two completely separate quality systems to support those activities.
All right. And a little bit more slow chart for you. Sumatra, did you want to speak to this a bit?
[00:05:05] Sumatha Kondabolu: Yes. Kelly, thank you for the kind introduction. So they take you through with a combination product where the CDMP requirements are applicable. So as Kelly was mentioning about in the previous slide about the single entity code package to products and cross level products, so here you will see that what the.
Specific applicable requirements would be when it comes to a single entity. So here one has to, the manufacturer has to make sure that the final rule is applicable which talks about especially for the combination product. If it is a drug specific requirements than 21 CFR two, 10, and two 11 would be applicable.
And also if it is a device, then obviously the 21 CFR eight 20 need to be applied for a single entity product, but it comes to the co-pack caged. There are two different routes that can be applied. It depends on the type of the product that is being manufactured. So if it is a drug company, so they the 21 CFR.
Beyond the 24 CFR two, 10, and two 11 would be applicable. But also one has to remember that the constant parks, which are specific from a medical device, then those requirements of the medical device belongs to the applicant. Especially when it comes to a coop packaged products. So the same rule would apply for the device company when the 21 CFR eight 20 for the quality system regulations would be applicable and some sections of the 21 CFR, two 11 and two 10 from the drug specific, those requirements would be applicable for the construction, but.
Then it comes to the cross labeled. So here it, more or less, it would be similar to the single entity bed of the 21 CFR two, 10, and two 11 would be applicable for the drug specific requirements. Similarly for the device, it would be the eight 20. So going ahead with the next slide, you will see that. Especially when it comes to FDA or if one has to apply the final rule or based on the 21 CFR part four, which is for the regulation of the combination products at the time, one has to make sure that the streamlined approach is the best approach that can be applied, where the specific.
Requirements for a product type that would be for example, if you take a drug, then those GMP requirements would be applicable. Whereas the remaining congruent parts would be from, if it is a device, then the device specific requirements like management responsibilities, or it could be designed special.
Controls specifically which derived from 8 20 30, that is the design controls and also the ISO 34 85 with the clause 7.3 from the design control. Those would be applicable. So similarly the purchasing controls is also very important going. In the next upcoming slides and be taking you through with the risk assessment.
They, we will talk about more on the risk factors that are associated with the purchasing controls. So similarly for the corrective and preventive actions, which would be applied both for the medical device, as well as for the drug company, which would be following. So one has to make sure that these requirements are aligned and followed current.
Within what the companies, whoever is responsible for manufacturing the device, and then they So there is another streamline approach, which I'll be talking about is the device. So if the manufacturer is a device company and they are implementing all the quality system regulations when it comes to the infants, especially, aligning with the treatment CFR four, section 4.4 at the time one has to make sure that they are also following the drug specific.
The requirements, which would be like, for example, the testing of the drug, or it could be the calculations which get into specifically when one applies all the required testing requirements, especially with the applicable regulations. Similarly, there would be a stability testing that is required and also the testing requirements.
And specifically one has to make sure that deserved samples, how they are being followed in compliance with 21 CFR two 11.170. And if we go ahead with the next slide here, you will see that the GMP requirement. When it comes to the structure development process. So where they for the pharmaceutical, it would be the ICH regulations that would be applicable.
And similarly, if it is a device, then the device specific regulations. If it is for us spaced, the targeted market is us. Then one has to follow the FDA regulations. So similarly it also depends on the product where it is being distributed. Apart from this ISO 1345 is the specific regulations. So for the medical device industries, so that need to be aligned with, and also as I was mentioning about the design and development phase, that need to be.
Compliant with these student relations, if it is for us and also for the other regulations as well.
Can we so the best approach for the drug and device development here, we will see the common pitfalls that drug companies face when they pursue the development of a combination product. So we will go ahead with the next slide. Here the development process, where we mainly focus on the basic research and also the prototype development with the design and discovery and where the preclinical studies, which.
Conducted going ahead with the early development phases where the clinical trials will be involved in, this is how the drug development will be conducted. Whereas when it comes to the combination product one both the companies, if they are working together, or it could be the same company who has been manufacturing, both the drug and the device, then the functionality and interaction, or especially the human factor studies.
These need to be evaluated. Based on the risk that is being associated both drug as well as the device. Kelly, would you like to talk about a few points on the development of the device?
[00:11:53] Kelly Stanton: Perfect. Thank you, Samantha. Yeah. It's always interesting to bring these products together and we're sick. Of course, we're seeing a lot more of this in the market. One of the biggest pitfalls that I've seen in my experience has been not enough or not robust enough testing around the drug device interface.
So what effects does this have on the drug? If it's a, if it's a novel packaging method, for example and I think, device, folks coming at it from that perspective are good about, thinking about user needs and how the usability of it, but maybe. Experienced in considering does this device actually have an effect on the drug stability or the drug purity or vice versa?
Does the drug have some effect on the device causing the device to wear or break down faster, for example, in storage? So it's very important to design some of your requirements and studies around. That drug device interaction or interface that, and I've seen a lot of companies get, oh it's just, it's a syringe.
We're going to throw a drug in it and package it this way. There's lots of different kinds of syringes out there with lots of different plastic materials and such. Definitely important to really consider that interaction and doing some of your development work around the finished product packaged together.
[00:13:30] Sumatha Kondabolu: Thank you, Gary. So here you will see that the design controls that help ensure a focus on the designing and the polity and incorporation of the relevant expertise during the device device development process. So one has to make sure that the drug consequent part, which has involved in the product development activities are related to its use.
Combination product. The design controls need to be in place for both the device as well as the truck. And one has to make sure that these requirements are being aligned and implemented across, throughout the design control.
Can we go ahead to the next slide? Kelly,
thank you. So here we see that the combination product consultations, specifically when to design control, start for a combination product. So we always say that When do we start, especially when it comes to a combination product. So here, one has to make sure that the company commits to pursue a commercial product.
For example, there should be a pre-submission plan. And that's how one has to identify all the specific requirements that are applicable for both the drug and the device, or it could be a biological product that is being involved. Combination product. So that is the case then the initiation of the design starts at a very early stage.
So that's how one has to make sure that the initiation of the design controls have been initiated. And those are being applied across the drug development process and also for the design development process. And drug CGMP is so there are no provisions specific to product development, but however one has to make sure that streamlined approach has been applied during this process.
Similarly, if there are any laboratory controls that need to be applied, that has to be identified and implemented in those specifications for the testing part.
[00:15:48] Kelly Stanton: And
[00:15:49] Sumatha Kondabolu: here we will see that each combination product that requires a design history fight. So when this design history file would be one, we'll be working on when the design specific requirements are being met, everything has been planned and then implemented for the design specific requirements.
All the details. We'll get into the design history files, and that's how the necessary design control elements are readily accessible. And also if you can see that the actual, the design history file information may recite in various locations it all depends on what are the different constituents and then the confidence or.
But it's limited to the device that it's being manufactured. So based on that, one has to make sure that all these are readily available specifically during the audit purpose.
And the design changes for the combination product. This is very important when it has to make sure that the if there are any design changes that will be affecting the overall product quality or else are these changes being communicated to the drug development team as well. So this is where both the design development team and then the drug development team.
To get it and make sure that all the changes have been met and those changes are applied across in all the processes and also leverage drug development process and practices during the design process.
And. This would be as I said, that all the implications of the specific requirements, but whereas when it comes to common pitfalls, especially when a drug company or a device development company would fall in this, we have seen, especially when, during the implementation of the quality management system, I have seen that there are chances of poor use case modeling.
A streamlined approach has not been applied across during the development process. Especially when it comes to the pre submission of the requirements to the , there should be a plan that is available. So that is how one would have, or phase these kinds of patients. Specifically if there is any incomplete user needs.
So if you see that the user needs are available and those have not been percolated across or shared with the different teams both when it comes to the drug company, as well as the device, then there could be issues that would arise from this similarly. Cross-functional teams. As I was mentioning to you, if there are any design change requirements or changes has been done, those need to be immediately shared with the rest of the team members to make sure that everything has been.
To meet the specific applicable requirements and also the pre-submission plan. So this is very important. One has to make sure that the plan is available and it is being aligned. All the processes are aligned based on this plan. Kelly, would you like to share some of the pitfalls or anything or any experiences
[00:19:10] Kelly Stanton: here?
Absolutely.
The number of times I've been involved in this where the team has a desire to not do the pre-submission process. And in the case of a combination product especially if you end up with all three branches of the FDA involved, for example they're all going to be looking for slightly different things.
And while once submissions go in. There's cross-functional review happening within the agency. Each branch is going to bring their own perspective. And so making sure that. You have those conversations upfront way early in development gives you an opportunity to ensure that you don't miss important steps as you're going through the development process, get all the way to the end.
And now have your submission to the agency delayed or. Full on rejected because you missed something important. The whole point of overlaying these regulations together and looking at these things early in your development process is to really streamline for later. There was a comment in the forum a minute ago about design control, not applying to drug development.
I would respectfully disagree with that comment. If you are developing a drug. For the explicit purpose of marketing that drug in a combination therapeutic, these are all considerations to have along the way. The good news about the streamlined approach and overlying overlapping. These regulations is for the most part, they're really not that different, putting together a device master record.
Is the recipe. And, for making the device is not different than your master batch record for your drug. So how you plug the pieces together to put, to, to tell the whole story of your product and using leveraging. Open, conversation with your regulatory authorities through the pre-submission process, you really can streamline your approvals for later and make sure that you're not missing pretty major elements of the requirements.
As you go along. So Samantha, I'll hand it back to you to talk about risk management and control.
[00:21:32] Sumatha Kondabolu: Thank you, Kelly. I be taking you through on the risk management and control strategies a bit a weekend focus on especially when it comes to the combination products. Within the company, even When it comes to the drug development or the drug manufacturing company, but the quality by design can be applied.
And similarly, the specific controls, which are a specific bill or device, those will be applied. But that is in device manufacturing company. The important part, one should focus on is the disc assessment specifically a proactive risk management is important. When it comes to the human factors, audit could be B a medication editor deductions, or it could be purchasing controls with one has to make sure that those areas are identified and a proper mitigation has been.
To make sure that the risks are not affecting the overall product quality and especially before, pre-market or post-market discuss assessments are also important. And also the change management, if there are any changes being made. So how this is being communicated, how the I can give you an example of where the medical device, like a loaded syringe or it could be the device which gets into a medical device as it append for insulin.
Administrator. So in that case if there are any changes which are made in the medical in the device, then if those changes are not communicated and the violets are being manufactured based on the previous drawings or the requirements. So that's where those issues would come up. So one has to make sure that those risks are identified and implemented across in both the companies or.
But the same company, that two different teams who are working on. And if you go ahead with the next requirements where the risk analysis. So as we all know that in, for the device, the risk analysis is based on the ISO 1, 4, 9, 7 1. So 2019 is the current version which is being followed. And for the, when it comes to the drug, it would be the ICH Q nine that need to be followed.
So here for the medical device industries, the risk assessment is already there as a part of the drug design device development, and all the risk assessments are recorded. There is a file, a risk management file that is available. At every stage or every phase of the design device design development, but when it comes to the drug device interface, that's where there could be some common pitfalls and one has to identify, make sure that these are being identified at a very early stage where the product is being developed.
And I would like to take you through with some of the considerations for both the truck and device that we can consider for specifically for the risk for the drug. It would be formulations where the identities trend as Kelly was also focusing or mentioning about the purity of the requirements that need to be focused on.
So similarly, the change in internet use that may impact safety and efficacy, and also. Physical discomfort if there are any physical discomfort associated, especially when it comes to the drug administration. So these kinds of risks need to be identified and made sure that everything is especially when it comes to the dosage liquid, the dosage is accuracy is involved in if there is an overdose or where I would also take an example of And drug administration, where there is a program involved in for the incident administration.
So at that time there could be some overdose or underdose. So these are all the different risks that need to be identified. So similarly for the device considerations, there could be product differentiations or maybe some technological characteristics that are involved, especially for the intended route of administration and also a clear unit.
Measured with one has to identify and make sure that. What would be the actual measures that need to be followed and it comes to the clarity of those completion. So what would be the, those completion when it comes when the device is being developed. So all these considerations need to be a teacher.
Prior, especially during the device development phase and also the drug delivery activity activation bit, the spring compression force required. So those kinds of minor issues also need to be evaluated specifically when one is developing the final manufacturing specifications before that all this need to be evaluated and recorded.
And also if there are any assembly lines for production scale-up so definitely there could be assembly product assembly. So what all the different requirements are required, the specifications are written down and also the applicable regulatory requirements that need to be followed during the inspection of the various assembly steps that will be performed during the production phase.
And he obviously that the overview of a typical quality risk management process with the risks should be considered during all aspects of the development. As I was mentioning to you before also that the design intent and based on that, what would be the usability of this particular device and based on the usability engineering requirements that needed.
Implemented and risk need to be identified. Similarly, continuous engineering verification. So they also need to be there. The verification steps are one has to make sure that those steps are followed and made sure that there is no major risks that are associated similarly the test of the device.
So overall, the test cases need to be developed in such a way that the risk assessment is aligned with those requirements and test cases. There could be like someone would come up with a few test cases in the verification and they say that, yes, my design verification has been completed. But whereas in, in the risk assessment, you might have not covered the specific tests that need to be followed.
Kelly, would you like to share your thoughts on the risk assessment specifically when it comes to a device?
[00:28:30] Kelly Stanton: Definitely. Thank you. Excuse me. I think you touched there briefly on using appropriate sample sizing. And that's often a question I spend some time with our customers talking about and there's a lot of good information out there.
On tying a sample size to risk assessment and how you go about proving those things. Unfortunately, there, while there's a lot of good information, there, isn't one specific formula that I'm aware of because the guidances and the and the regulators expect you to determine that for your product. So it's important to really see.
Back at a high level and look at risk management overall, always keeping in mind, what is your intended use? What is your label claim that you're trying to make here with this product and starting from that place of really understanding what you intend your product to do, and then start diving into, okay.
What could go wrong? Make sure you've assessed those things and you don't have to get crazy. This isn't three fault layer. If this, then this kinds of scenarios unless you have evidence to believe that something in. Super complex scenario has actually happened in maybe a similar product on the market, or if you're developing a new device to deliver an already approved drug, that's also a really good place to start.
Make sure that you've pulled that information into your entire process and then tie that back justifying. Document those justifications. That's another place where I see things get missed. The design team sits around in a room and has these conversations, but it doesn't always write everything down.
So sometimes it's hard to go back, think about future you needing to understand why a decision was made way back in, in your early development. I think sometimes the research guys are hesitant to write those things down. They don't seem important, but as someone who has spent many years on the commercial side of the fence, trying to, deal with issues that come up in the field, I have found myself often going clear back into R and D notes trying to find more data or more information around those sort of one-off failures or use cases that have.
Making sure all of that stuff makes it into your risk management files and you have taken a stance on this is what we believe the risks are, and this therefore justifies the sample sizes that we did during testing. And whether or not you need to test that device to the point of failure. That's another place where I think things get missed.
Again, reasonable expectations. You don't need to go nuts with, every possible, way that this thing could fail, but you definitely need to have thought about that for your device and your drug. What are those known issues? Wherever possible.
All right. So on the control strategies side of things and how to address. Some of those things that we've been talking about going through your whole risk management program, making sure that you've identified those risks. What are you going to do to address them? Purchasing controls, materials, specifications supplier quality agreements in the scenario where you're dealing with outsourced manufacturing.
Especially on the drug side the requirements around quality agreements and contract manufacturing arrangements that's changed more recently on the drug side of the fence than it was, in device we've been doing those kinds of things for years. Drug it's newer. It's interesting to me that even though this guidance from the FDA went into effect gosh, five, six years ago I still have clients run into raw material suppliers who won't do a quality agreement because they're like, why do we need to do this?
Cause it's the guidance say agency expects it of us. So really making sure that you understand. The quality systems in place at your suppliers at your contract manufacturers, et cetera, et cetera. What in process manufacturing, controls and release testing are necessary. This again, should tie directly into your risk management files areas where there's high risk of something going wrong that could possibly injure a patient.
How can you control for that in your manufacturing process? So those things never. Off of your manufacturing line. That's all really important which leads into manufacturing control plans. So again, incoming inspection, release procedures, incoming specifications your inspection and release process to release those materials or components to the manufacturing process.
And then how are you dealing with things that don't conform? So you're nonconforming. Product disposition decisions and it's really important to as well in that non-conformance process that you consider. Is there an impact from a device regulation perspective and a drug regulation perspective?
Even if you're the COO making the device side of it and not making the drugs. Is it possible that you could make a decision about the device in a vacuum that could have a problem or it could cause a problem with the drug itself? So anytime you're intending for these things to be used together the.
That, that interface, that how they interact with each other always needs to be in the, in your thinking packaging and labeling controls. And I think we'll discuss labeling in a bit more detail here in a few moments, but controlling the packaging and labeling materials across components suppliers, manufacturers making sure that's all defined.
And then final testing and release final acceptance inspection, release procedures, specifications, again, that non-conformance process and all of these things, while, perhaps the final release testing is governed under a two 11 regulation around test method validation. It doesn't mean that it's also not part of your device history file, your DHS records, right?
Because that is part of the recipe for how you make the entire product.
Oh, some new regulations in play. I believe Sumatra. You've got this one.
[00:34:50] Sumatha Kondabolu: Thank you Kelly. So the new regulations for combination products. So we will see what are the different regulations and then how they are applied for the combination products. So starting with the guidance on for industry from FDA, this is on the current good manufacturing practice requirements for combination products.
This has been aligned based on the 21 CFR part four for the regulation of combination products. And similarly health Canada has come up with a drug device combination products, which is still in a drought status for a consultation. And also when it comes to the EU requirements European requirements.
So European medicines agency has put a guidance document in place, which is still in draft status on. The guideline on the quality requirements for drug and device combinations. And as I was mentioning about in the risk management phase with the ISO 49 71 is applied for the risk assessment for the devices, but whereas AMI they have come up with.
Standard, which is specifically designed for the risk management guidance for the combination products. And I'm doing the next slide. I'll take you through support. Keene bottom points that are focused in these regulations. So this guidance from FDA, it focuses mainly on, or it is based on the final rule from 21 CFR part four.
So this guidance describes and explains the final rule on GMP requirements for the combination products in section one. So there are a few sections which are being mentioned total. Five sections. So section two is in this document is on how the, what is the combination product? What are the different types of the combination products that has been focused on?
So similarly, if you see the certain general considerations for the CGMP compliance for combination products, and also the content that is specific for the. CGMP requirements based on the final rule and also how these scenarios are applicable across in the GMP requirements, then one has to apply.
So this guidance document has been designed, but. If you see if you find anywhere as showed, that means it is not mandate free. That's how this guidance has been designed. It is only a recommendation for the manufacturers or who are involved in manufacturing, the combination products.
So going ahead with the focus on the 21 CFR part four, which is a deregulation of combination products, and this is focuses mainly on the requirements for the. Drug specific requirements would be aligned based on the 21 CFR two, 10 and two 11. Similarly for the devices this regulation guides that the manufacturer has to follow the CFR eight 20.
And when it comes to the biological products. So there could be, as we have focused on the various different combinations. So when it comes to biological products, so both 21 CFR 606 80, that would be applicable. If there are any tissues, so human cells, tissues and cellular or tissue based products when they are applied.
So it would be 1271 that comes into place or one has to apply for that combination product.
And when it comes to the health, Canada and health Canada requirements, or the requirements that need to be applied with the company specifically, if it is a class two and about classification of the medical device at the time, the requirement would be that the medical device licensing has to be.
Priority in place. And then if they are putting it in the market before that one has to go for the medical device licensing and also all three classes are required to satisfy the national standards of Canadian requirements based on the ISO 13 45, 20 16 specifically that has been designed for, or applied for the medical devices, the standard.
And that is another key important point. One has to focus on if there is a class to end up out device, then the medical empty step that is the medical device. Single audit program will be applied if the manufacturer is in Canada.
So what could be the key important requirements when it comes to the Canadian regulations? Those are like, if the products are classified as a drug device combination product, then. Drug delivery systems that are combined at the time of manufactured or if they are co packaged. So these would be considered as a drug device combination products.
So similarly the drug enhanced the devices, or it could be device enhanced to drugs. So this all will be classified as when it comes to a kids or cross labeled product. Companion diagnostics, but Netty combination drugs, or it could be the equipments that are used for the manufacturing of the trucks.
Those are not considered as the daily CP. Yes. When I mentioned about cross label products please make sure that if they are individually authorized and sold separately, then at that time the label to be used together exclusively then in that case, those are not transferred as the drug device combination products.
And here then it comes to the European medicines agency. So they are they have come up with a draft guideline, which more or less focuses mainly on the integral drug device combinations and also the EU requirements the new requirements from UMD, those are aligned based on the article one and article nine paragraphs of, from the article one.
So not integral. Drug drug device combination products that are two or more separate competence are available. And in that case, they are being classified. Similarly, something similar to the health, Canada regulations, health, Canada regulations, and before they are out of scope would be, if there are any combined.
Requirements from the active substance or from the formulation, or it could be big Canadian drugs that has been manufactured or in vitro diagnostic devices. These are not considered as combination products.
So the risk assessment when it comes to what guidance or guidelines need to be followed at the time It's always made clear that I sold 9 71 would be applicable when it comes to our device. Regulations need to be applied. But whereas the, this AMI is the technical information report that has been released recently in 2020.
So here the specific important requirement would be that they recommend if if the manufacturer. Are following the risk assessment, how the approach needs to be followed across during the development of this combination products that is focused mainly in this particular technical information report.
So that is how one can apply both the, I support 9 71 as well as the requirements.
Going ahead with the labeling requirements. So how the labeling requirements would be applicable. And if you see the primary component of the combination products, it would be that the gender labeling requirements which are applicable both for the drug and then the medical device. But, whereas when it comes to the actual European regulations, one has to make sure or should not get confused is the CE mark.
So because for a device, it has a seen mark. The Mark May be included on the device itself, but not, it should not be labeled on. Drug or the combination product overall combination product. So that is very important. One has to make sure that is being complied with, and also the outer packaging and that the package leaflet may not only include symbols or picto grams if necessary.
So that needs to be made sure. Specifically for that European regulations when the manufacturer is compliant or planning to distribute the product in Europe.
[00:44:13] Kelly Stanton: All right. I think we have reached the end of our presentation. I do see a new question in the chat. We've been trying to answer them as we go along, but Sumatra, I think you might know the answer to this one. Do I understand correctly that the IVD drug products for example, companion diagnostics are considered combination products in the U S but not combination products in Canada or EU.
[00:44:39] Sumatha Kondabolu: Yes, Kelly. When it comes to the combination products, especially the IVD in EU, yes, it is not considered, but whereas even us if it is a kit, then it may not be applied, but if it is IVD, yes, those requirements need to be made. Sure. It all depends on the regulations or the product constantly constituent parts, which are involved in based on that those regulations will be applied.
[00:45:11] Kelly Stanton: Are there any other questions? Please feel free to put those into the Q and a box.
All right. I believe the slide deck has been provided to everyone in the chat box, as well as the recording for this will be available.