0:03
So welcome everybody and I would like to thank the organisers for allowing me to speak.
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So I will talk today about a novel solution that we have established which we can use for vaccine manufacturing as it stated here.
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But it can definitely also be used for viral therapy production if needed.
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I will start off with a company introduction of Batavia and then I will tell you a little bit more about our development platform.
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So Batavia has a has a global presence.
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We are located in Leiden in the Netherlands, but we also have a location in Woburn in Massachusetts near Boston.
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And we also have affiliation with our CGA headquarters in South Korea and an office in Hong Kong.
1:00
The facilities in Woburn, MA, is an R&D facility that has lab space for about 1200 square metres.
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And our headquarters in Leiden has an 8000 square metres for R&D.
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And on top of that, we also have a GMP facility in in Leiden that will accommodate phase one and phase two clinical trial manufacturing.
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Very soon.
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We are able to expand our capabilities in Leiden even further because we're in the process by help of an investment of a company CJ to build an additional GMP facility in Leiden, which allows us to also do phase three and commercial manufacturing.
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It will be a facility that will have about 12,000 square metres of production space in total, six production suites.
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We can produce in that facility, up to 1000 litre scale.
2:03
And of course we'll have a state-of-the-art fill and finish possibility as well and robust platform usage of which I will tell you more later.
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The vision of Batavia is to reduce human suffering from infectious diseases and cancer.
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And our mission is therefore also to be recognised as a centre of excellence in biopharmaceutical R&D and clinical manufacturing.
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And one way that we want to achieve that is to really work together with you and become a partner.
2:40
And our aim is to bridge the gap between early discovery and late stage commercial manufacturing.
2:47
And also in the near future, we can also take on the late stage commercial manufacturing as soon as our new facility is up and running.
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And the way that we want to bridge this gap is to work on process development and do clinical manufacturing phase one and two.
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And our bridge is built on 2 pillars.
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1 is partnership, as I already said, but the other one is quality because we, of course, do aim to deliver high quality materials.
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Our track record is that we are a process development powerhouse, and we were working with more than 100 experts with industry experience.
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Up to now we've done more than 500 projects successfully, 97% of successful runs in GMP and we have about 70% returning customers.
3:42
And our expertise is on viral vaccines, viral vectors for gene therapy or oncolytic virotherapy.
3:51
We do process development, thinking of upstream and downstream process development, but also analytical developments.
3:57
We do technology transfer, and we make in the early stages pre-MVS material, which is basically pre-clinic, pre-GMP material.
4:08
And we and we do cell line generation. And for manufacturing we do cGMP manufacturing, we do stability studies, virus and cell banking if that's required.
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We produce research or tox material that’s also required, and we provide GMP release and regulatory supports.
4:29
So now a little bit more on the platform that we want to talk to you about today.
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If you're working with viral vectors, for example, also for your oncotherapy, you may know that if you want to produce them.
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And particularly if you get a low yield, that you are already looking at for GMP capacity at high cost.
4:53
Because if you have a relatively low titer production, you automatically will also need large capital investment for your GMP construction because you will need a high amount of production ability.
5:09
Then you of course you have a relatively low output per square metre floor space.
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So meaning a high CapEx.
5:16
You also will have a high OpEx, because those types of processes are labour intensive, they're costly, they're large and you need also, as I already said, a large facility.
5:28
And then on top of that, low process yields or long bioprocessing times and many steps that you have to do, you end up with a high cost of goods in the end for your products.
5:40
One of the things that we also look at when we work with our clients is first of all, we want to make sure that the client gets a production system that is scalable and that is well set up.
5:53
Because if you set it up from the beginning and it's not only just for your phase 1-2, but you also think ahead that you have to go towards Phase 3 and commercial.
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That's how you can basically start off with the right process from the beginning.
6:07
So when we work with our clients, we design and develop production processes and then of course we look at optimization of cell cultures, optimization of your transfection or infection protocols, all to aim at a maximised yields and quality of your upstream processing.
6:25
Downstream processing, of course, we look at improved product purity and recovery. Also, there the system must be scalable and cost effective and minimise the time and the amount of unit operations and you cannot do it all also without doing formulation development or developing your assays that you will need for testing and release.
6:49
On top of that, of course, we prepare all the manufacturing and release documentation that will be required, and we will in the end produce the products.
7:02
And, then I basically get to our technologies because we've been thinking of how we can make sure that we have a very scalable but also a well enough USP system that that allows for a good cost of goods in the end.
7:19
And one of the platforms that we have established for this is our HIP-Vax platform.
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And I will tell a little bit more about it.
7:27
So the HIP-Vax platform, it's based on this novel type of bioreactor, which is basically a fixed bed bioreactor.
7:35
And as you can see here in the picture, it's built off a membrane that is folded around on multiple times and it's fitted in a relatively small bioreactor.
7:46
If you're working with adherent cells, they will be able to bind to this membrane and on both sides.
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So you can imagine that you have a really high number of square centimetres to which your cells can adhere and grow on and the medium will continuously flush through.
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So your cells will get a continuously fed during the during the production process.
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And the benefit of is that it's a high density because it's a large amount of square centimetre in one bioreactor.
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And it's also set up so that you will get a good homogeneity.
8:29
And this is basically what the system will look like in total.
8:32
So this is the pilot scale, which is the mid-size scale.
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It can be a 10 or 30 square metre of adherent surface.
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This system is set up such that it actually fits within biosafety cabinets, but you can also put it on the lab bench depending on what's possible.
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We use this system for proof of concept studies, process development studies, but also for GMP production phase 1/2.
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And by default this system is run as a circulation mode, but it can also be run as perfusion.
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And there's a possibility to use an inline concentration setup.
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And this is actually the bigger brother of the system.
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This is the system that this actually meant for commercial manufacturing.
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It has a surface of 200 to 600 square metre for cell adherence and this is run preferably with an inline concentration setup.
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When we use the system.
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What we of course wanted to do is because it's we wanted to see if we indeed will get a higher amount of cell density within the system.
9:56
We looked at this for both Vero cells and MRC-5, and indeed, we were able to get higher cells per mL densities for both cell lines compared to the other systems, for example T-flask or Microcarriers.
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Other thing that is very important especially also when you do process development, but also if you go from phase one to commercial is that you want to make sure that these systems are scalable.
10:24
So there is a small scale variant, there's the pilot scale variant that I showed already, and then the commercial.
10:30
And what we've been able to show for Vero cells is that the cell density of infection in all these systems is really comparable.
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So it means that the system is scalable.
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You can start off at a smaller scale and then go up commercial and then indeed also expecting the same result.
10:54
And that's the same is also true for virus production on the systems.
10:57
That's it's really comparable whether we use the small system, the pilot scale system, or the commercial system, regarding the virus output.
11:10
And as I already said, the system can be set up with an inline concentration step.
11:17
And if we do that then for example for the small scale set up which is 2.4 square metre, you get a harvest of about 240 millilitres.
11:27
For the pilot scale which is the 10 or the 30 square metre, you will end up with one or three litre of harvest material.
11:35
And the commercial scale, which is the 200 or 600 square metres, you can end up for 20 to 60 litres scale.
11:43
And especially the commercial scale, it is in comparison equal to about the 1000 litres of microcarrier process.
11:51
So you can also imagine that if you're able to concentrate your harvest in such a way that the next steps of processing will also be shorter and more cost effective because there's a lot less volume to work with.
12:09
We've set up this this HIP-Vax technology now for several different projects in collaboration with Global Health.
12:17
We've had a couple of projects based on the VSV vector that were successfully into GMP manufacturing, and some are still in R&D.
12:30
We also had a successful one for rubella and measles both also at GMP stage.
12:39
And within R&D we're also working on inactivated polio virus or oral poliovirus vaccine manufacturing with the system or a vaccine manufacturing with the system.
12:54
And also one thing that I said upfront, the aim that we have is to reduce the by the system the cost of goods for such products and for a couple of products we have successfully done so.
13:08
The aim was to achieve a cost of goods below $1.00 per dose.
13:13
And for the trivalent as IPV vaccine, we managed to reduce the cost of goods to $0.50 per dose.
13:24
For measles and rubella it even went down to $0.15.
13:30
And for the VSV-vector technology that we've set up, we were able to achieve a reduction to $0.70.
13:43
So to summarise the benefits of the HIP-Vax system, it's a suitable system for gene therapy, oncolytic viral therapy, and viral vector vaccines.
13:54
It reduces the time for the bands to clinic in nine months.
13:58
If you work with the system that is set up, we are able to reduce the cost of goods for a vaccine below the $1.00 cost per dose.
14:11
1000 litre output of suspension by reactor system is reduced to 50 to 100 litre harvest or can be reduced in a 50 to 100 litre harvest in this system.
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You can achieve high cell densities for both adherent and suspension cells.
14:27
If the inline concentration is possible, you will end up with a concentrated harvest, which opens all kinds of possibility for the next steps or even other product delivery technologies.
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We've shown excellent scalability from R&D to clinic and commercial scale, and we've proven qualified under clinical GMP conditions.
15:01
So for that we would like to acknowledge our partners, IAVI and Univercells to work on the system and our funders, the Bill and Melinda Gates Foundation, CEPI, and DTRA.
