ICOpre – the story behind a new, generic inhaler platform to Ellipta

Iconovo has developed a new and innovative dry powder inhaler platform – ICOpre – aimed for a global market. ICOpre is a pre-metered dry powder inhaler for simple, once-daily treatment, containing 30 individually sealed doses.

Welcome everybody to uh this workshop by ikenovo it will be a workshop about the development of a generic dpi platform for a global market and i’m auras lastov the founder and currently the cto of iconovo some background about our company is that we’ve been founded for almost seven years and have grown significantly to 29 employees and we are based in lund in

South of sweden at the old astrosenica site which is now american village we have all the capabilities in-house we do engineering device development formulation and all the analytical work in-house in our labs with our staff we are currently listed on nasdaq stockholm so we’re publicly traded and we deal with with entire development of a dry powder inhalation

Product why do we do this well you can say that we develop products for people with diseases to the lungs it’s mainly asthma and copd and it’s over half a billion of people suffering from those diseases and those those are chronic diseases that cannot be cured they can be managed and we develop drugs to help people manage their diseases and we’ll be doing this

For a while and now we are entering a new segment when we are looking at the family of the jsk ellipta products uh which is the like the new world-class uh platform of of inhalation products and as you can see they are selling very well very well uh over 3 billion dollars annually and it is a franchise that we are have entered to develop a generic product family

And the challenge here is to match the expo expiration of the patterns both of the drug and for for the device and as you can see the the drug expiration is uh beginning 20 already 2021 but the main main one reload is 2025. so that’s our main target to have our product ready for that expiration then there is expiration also of the of the device which hinders people

From entering with a device which is a copy which is a exact carbon copy of the original and for that reason we have decided to develop our own inhalation device which does not in any way infringe or mimic or the elliptic device when developing these products you you need to attack them from from two sides one is the device and then also the formulation and

In in those products uh you also always have two different formulation in every product so it’s a combination product with one api in each uh powder or sometimes in in the triple case you have two apis in one and one in the other and we do development of both the device and the formulation ourselves in-house and that’s what we offer to our our partners developing

This kind of products is is very challenging especially if you’re targeting the us market the fda has very rigorous a very detailed requirements and guidances of what what you need to achieve to be approved as a generic so it’s several kinds of equivalence that has to be proven we need to have a formulation that’s equivalent we need to have in vitro equivalence

Prudent and also in vivo equivalents so those are very very challenging uh requirements that we must meet but we we know this from the beginning so we we have this on on a target on our radar from the beginning and we develop a product especially to meet all those requirements and then also we need to have a product that is it’s equivalent in terms of use it’s the

Flow resistance the use of handling et cetera so for the patient it must be very very similar and nonetheless it must be low cost manufacturing must be fairly simple and easy to manufacture and also completely non-infringement in terms of the original patents when we did this product development we started off by setting up a high-level specification we did a

Very very uh thorough analysis of the original product of the lipta portfolio and decided what features do we need to have and what metrics do we have to meet and of course we need to have the same kind of formulation the carry-based formulation and also have the same performance which is this is key for of course the pharmaceutical and in vitro the clinical

Performance and also the in vitro performance and it’s uh pre-filled it it has the same kind of uh humidity protection as the original and we have a dose counter of course and it’s handled in the same way it’s open inhale close divide so this is uh is the absolute must but we have also decided to introduce some features to help the patient to be more safe or

More confident in the use and also uh to improve compliance so we we have introduced a load indicator showing that when the when the device is loaded and it’s ready for inhalation there’s a visual indicator showing us loaded ready for inhalation and then after inhalation this changes to a clear indication successful inhalation the drug has been delivered you have

Received the dose and this is to to make the patient feel safe and confident when using our product uh when starting off doing this kind of development of a brand new uh from from blank paper kind of device there are a few things you you need to consider first and you can say that the this this kind this class of devices they have the certain anatomy as i call it

So you have you have a cavity that is filled with drug that is sealed to protect it from humidity and dirt etc and stopping it from falling out and then during use by the by the patient you in some way open the cavity you remove the foil or lid or whatever and then you inhale and those steps are in all of those inhalers so we need to solve this uh this task in

A novel in uh innovative way that stuff that does not in any way infringe the original patterns and this is a very very important uh decision early to make in such a development so either you decide to do a copy of the original which means you use the proven technology you can you get 3d scan and and do uh like a carbon copy of the original and that’s uh from

A technology point of view a safer way because disapproval technology and you know that it works as long as you are able to copy it properly the con is obviously that you are you’re risking infringing the patterns and in the ellipta case there are patterns protecting the technology until 2030. that’s almost 10 years from now so this is a long long duration of

Those patterns and that closes the door for those devices based on being a copy the other choice you can make is to develop your own new technology which is don’t use a blister strip use something else come up with something new innovative novel and that’s that’s the route we have decided to take so we have our own technology that is we have patents pending

And it’s completely different from the original and i think that this is a key strength of our product that we can launch this product before the expiration of the patents currently the elliptic patterns the device patterns there are six patterns covering the device and aluminum strips and so it’s six patterns that that protect that technology and so we have

Decided to have a technology which is based uh on injection molded disk so instead of an aluminum blister strip we have an injection molded disc with cavities and this this disc is filled with drug sealed and then opened with our own novel innovation i cannot show you any details of that because we just few months ago filed our first pattern so this is still

Very sensitive to show publicly so i can only talk about it in principle so what we do we have we have two circular disks filled with with cavities filled with drug they are sealed with aluminum foil and then we have some kind of operation that we do that opens both cavities simultaneously and then you inhale emptying both cavities simultaneously and the drug

Is delivered and how how those discs are designed how we seal them how we open that that’s covered in our pattern so i cannot unfortunately not go more deeply into that so what do we have we have our ico pre it looks like this this is a real life size with a dose counter here we operate by opening like this very similar in terms of handling to the ellipta

And a clear dose indicator so in this case is equivalent to the ellipta but inside is completely different so how did we go about in this development because this kind of develop and when you do like a massive parallel development of device formulation analytical methods all the documentation documentation it’s a lot of hurdles it can be very uh costly and very

Risky if you don’t go about it in in a smart way so the way we approach it is that we see we see it as a product we don’t see it as a device and a formulation we see it as a product and this product has like four parts uh so it comprises four parts one is of course the formulation one is uh the mechanical side of the device one is the filling of the drug into the

Device and the fourth one is the ceiling the aluminum foil inside so we develop all of all of those in parallel in the same labs same people involved so we have analytical people involved in all this development where engineers develop involved in the formulation of filling and sealing we have pharmacists developed developing the feeling and sitting as well so we

We try to have a cross-functional group developing this in concert uh to to boost really the understanding and the engagement and the commitment to develop a product i like to show it uh illustrate like this with like four parallel arrows so we develop everything in parallel and it’s pretty much uh the same team of people working with different parts of this and

I think this is extremely difficult difficult to do if you are not a real team working jointly i know examples of companies where the formulation development is done in one city and the device developed in another city sometimes it’s different countries even and then you you don’t have this very close cooperation even in some cases if you have the formulation

In one building and analytical in another building you don’t get this joint effort and joint engagement in the development that you we achieve by mixing the people working together in the same labs so this gives us a excellent understanding of the product from different aspects so we have the pharmacist input on the device we have the device people’s inputs of

On the formulation of the analytical testing etc so this enriches our development and it makes it uh less risky reduces the cost and also the development time but of course there are a lot of challenges that we need to address and we need to solve in uh in this exercise so for the formulation we need to have humidity control labs we need to have all the

Equipment available we need to think about how to scale the process up how what the batch size is how do we transfer it to the commercial manufacturing when it comes to filling we need to do some filling initially small lab types of filling and that have the same technologies being able to scale up to a large scale feeling and and in that case both in the

Filling and ceiling you need to very early in the project connect with partners that can help you throughout the process the device it must be low cost manufacturing low port count simple processes a suitable fully automated assembly and of course the testing you need to have very integrated testing of the product another uh very very challenging aspect is that

When you develop everything at the same time how do you prototype how do you test if you don’t have a ready formulation how do you test the device how do you develop a formulation if you don’t know what the device would look like so you need to do this in a very clever way early on so you have like model formulations model geometries of the device that you can

Optimize them in peril even before they are finalized and this is very challenging because everything interacts with everything so as i try to illustrate with those arrows so in order to manage this we like to say in terms of the device we started off by having like a unit dose version of the device with just single cavity then we scale it up to have multiple

Doses but instead in a circular disc we have on a linear linear strip because it’s easier to test easier to feel and then we move on to the final shape which is a circular disc this is the way to to facilitate early testing and optimization of the formulation and some features of the device when it comes to filling we start off with simple spoon feeling then we

Go up to like small man manual scrape filling and then we go further on to more benchtop simple machine type of feeling using the same technology as uh in a commercial case we also do a lot of uh computational fluid dynamics to optimize uh the geometry inside of the device so we i cannot of course show you the real uh simulation because then i would uh show

The geometry inside but this is this is uh you can say emptying of a cavity i can i think i can show that so we simulate how the air flows inside the cavity what kind of turbulence you have and how well you get the air into the cavity uh break up a powder and empty it so all of this we can we can simulate uh doing cft and use that to optimize the product in

Terms of formulation development we are developing five different separate formulations and those are the formulations that actually make out the whole ellipta portfolio so we have two fluidic assault formulation one of the lanteral one homocledius and one combination umecladio and velanterol formulation so we develop all of those at the same time and they can

Then be combined differently to make out the different ellipta products i’m very glad to be able to show you this because we already have data using our inhaler our formulations tested in ngis in our labs and comparing them to the original ellipta so this is we use the relvar as a comparison and here you can see uh the left two uh bars are the high strength

Relevar so to the left you see our fine particle fractions the the blue is fluticasone the orange is velanterol and compared to the ellipta and both the low strength and high strength we are very close already and we are very very early in the development of formulation and very early in the development of the device when it comes to the fine particle dose which

Is clinically the relevant metric we have very good results but we are slightly slightly lower than the original which means that we need to increase the fill weight in our in our cavities but we are as you can see very close already to meet the requirements that we plan to meet four years from now thank you very much

Transcribed from video
ICOpre – the story behind a new, generic inhaler platform to Ellipta By Iconovo