- 2 days ago
by Christoph Hüls, Founder Additive Manufacturing of Tablets, Merck Innovation Center, Merck KGaA
Additive Manufacturing of Tablets has the potential to simplify the manufacturing of pills (tablets). Instead of a multistep complicated process, a three step process (mixing a powder formulation, printing the tablets in the printer and coating of the tablets) will lead to cost and time savings for customers.
In a strategic collaboration with AMCM GmbH, Merck is introducing the technology first for clinical trial supply, addressing the pain points of the pharmaceutical industry of very costly and long pharmaceutical drug development. The technology holds also the potential to decentralize the pharma production in the future by scaling the production with printers installed in the growing markets. The technology has therefore the potential to bring urgently needed medicines faster to patients.
Additive Manufacturing of Tablets has the potential to simplify the manufacturing of pills (tablets). Instead of a multistep complicated process, a three step process (mixing a powder formulation, printing the tablets in the printer and coating of the tablets) will lead to cost and time savings for customers.
In a strategic collaboration with AMCM GmbH, Merck is introducing the technology first for clinical trial supply, addressing the pain points of the pharmaceutical industry of very costly and long pharmaceutical drug development. The technology holds also the potential to decentralize the pharma production in the future by scaling the production with printers installed in the growing markets. The technology has therefore the potential to bring urgently needed medicines faster to patients.
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TechTranscript
00:03So thank you very much for the opportunity to speak here, it's a very interesting conference
00:07and I would like to introduce to you now our activities in going forward for 3D printing
00:14of medicines in the future.
00:16We even call it digitalizing the production of pills or tablets because we think this
00:22is really a very different approach into the market and I will show you in my last slides
00:27what we mean by that.
00:28So I'd like to show you how we came to that area, what we are currently doing and what
00:35is then in the end our vision.
00:37But maybe first let's see where this idea came from.
00:43I'm working for Merck, that is a German company, family owned.
00:48It is, we call it the oldest pharmaceutical company in the world.
00:52We celebrated in 2018 our 350 years birthday.
00:57We are active in three business areas that are depicted here in these pinky areas that
01:06is healthcare, life science and performance materials.
01:09I'm working in a central innovation unit that is tasked to generate new business for Merck, that
01:16is either combining expertise of these expertise that we call innovation between, or that is
01:23outside of the existing strategies of our businesses and that is what we call innovation beyond.
01:29In fact, this is in some way both because we are combining here expertise from our life science business in
01:37excipients with the certainly drug development expertise in healthcare and we are also developing the next generation production technologies that
01:46is even beyond what is done in current technologies in life science and healthcare.
01:52The central innovation unit is certainly dedicated to first establish innovation culture in the organization, but is also, as I
02:03tried to describe also in the previous slide, dedicated to bring business forward into the market.
02:11And therefore, I mean the light blue bubble here, that is, that is meaning that we built a strong internal
02:17innovation project portfolio.
02:19In fact, we are with this really going forward to the market.
02:23We are in the commercialization phase of this activity already.
02:27That probably as a kind of introduction where this project or this activity, this business came from, our vision for
02:37this is that we really 3D print medicine in the future in some way, really substituting some of the technologies
02:44that are currently used in let's say the classical way of producing pills, tablets, we would like to revolution some
02:51revolutionize a bit this production environment for tablets and pharmaceuticals.
02:56And certainly, and certainly this whole area gives a possibility to lead to digital design and very tablets, I think
03:05this community is quite aware of that, but with that, you are also enabling a digitalized decentralized production, because you
03:15are trying to print print them in the markets, the medicine, I will show you later what I mean by
03:22that, but let's dive into this.
03:24I think I think I don't have to explain to this, I think I don't have to explain to this
03:28community this slide, but I want to certainly mention that all these technologies have their application in this area.
03:37On the left side of the FDM technology, you heard a lot already, we heard from a pre-share around
03:44the binder jetting.
03:45I'm going to focus more on selective laser centering now, and I will show you in the next slides why
03:50we are focusing in this particular activity that I'm showing today on laser centering, but I want to re-emphasize
03:59all these technologies will have the applications we think in the future.
04:03It's just that we have chosen for our way forward, the right side, and the reason being is here is
04:10somehow described in this table.
04:12If you compare the different existing and let's say future 3D printing technologies in this area for pharmaceutical production, you
04:23certainly have to compare certain properties like appearance, mechanical properties, the cost per tablet, the throughput that you can achieve,
04:33batch sizes you are considering, and so forth in the different technologies.
04:39And maybe I have it right or wrong, but let's say in some way the numbers presented here are right,
04:48then we have chosen the laser centering powder bed fusion technologies because the appearance, the throughput, the cost per pill,
04:58and the time for formulation development is somehow in the sweet spot for the application we have chosen, and that
05:05is clinical trial supply.
05:09And certainly we have chosen.
05:10And certainly we have looked into this in more depth.
05:13I don't want to show here the technical details, but in our technical studies, we could clearly show that using
05:20this technology, the shape is in the specification that is required from the regulatory bodies.
05:28We could clearly show that the roughness, that the roughness of the surface, that the roughness of the surface is
05:31acceptable, that the mass of the tablets is in the expected specifications, as well as the hardness of the tablets,
05:42the mechanical stability.
05:43Then what is very important in the pharmaceutical setting is certainly that the active pharmaceutical ingredient, the API is uniform
05:52distributed in the different tablets produced, and it should not be degraded.
05:58So no side product should be visible in this production process.
06:04And since our laser centering approach is also using low temperature, around 60 degrees, we also see no degradation of
06:14the active pharmaceutical ingredient using laser centering in our approach.
06:18What is also then important is certainly that the dissolution profile is acceptable, and when we tested this in comparison
06:27to selected normal, let's say, fabricated and normally produced by tablet pressing tablets, you could see that the dissolution profile
06:38is quite comparable to the traditional manufacturing methods used.
06:43So therefore, there was a decision to go forward with this technology, and we think that by now using this
06:53technology setting, we can really avoid a lot of complexity in the normal production process.
07:05I think you know it probably that there is a plethora of different steps used in the traditional tablet manufacturing
07:14process, from milling the different excipients, APIs and powders, to blending them together in a formulation, and make a granulation
07:24of these so that the size distribution is in a way that there's no separation of the four powders, and
07:30that you can really work with them in the classical tablet pressing machines.
07:34Then you have to lubricate this whole formulation powder, then you have to lubricate this whole formulation powder, then comes
07:39the classical pressing of the tablets in a pressing machine and a tableting machine, and in the end, you have
07:47a coating of these tablets still to do.
07:50So we think that with our technology approach, we can really do it in a three step approach in some
07:57way, like mixing printing done, you just have to mill and blend the powders into a formulation.
08:04And in our experience, formulation is much easier, much less complex, it only contains less of these excipients for the
08:13whole process, then comes the printing process in the machine and that is kind of the picture from our machine
08:22that we have in our premises.
08:24It is an industrial size machine, it's not a tablet, it's not a tablet, not a tablet, not a tablet,
08:28not a tablet, not a tablet machine, it's, it's really something that is, you know, meant to be in and
08:32ended up used in an industrial setting.
08:35And then we still have, because the roughness of the tablets is just not acceptable by the patients in the
08:41end, we still have to do the coating of the machines like in the classical printing, the tablet manufacturing process.
08:49But as you can see, a lot of steps are avoided, that means run up losses of the formulation is
08:55not there, means we have less consumption of the very expensive active pharmaceutical ingredient in the clinical development.
09:03Just to give you an impression, a kilogram of active pharmaceutical ingredient in these early phases of drug development, the
09:12synthesis process, the production process of the API is not optimized, the kilogram of the API can easily cost up
09:19to 200,000 euros per kilogram.
09:21And if we save here, a few kilograms in the process, a classical phase one production is consuming about 10
09:29kilograms of active pharmaceutical ingredient, and we think we can work with three to five kilograms, then you can see
09:35already a benefit to our customers here in using less API for the formulation development and the production of the
09:42clinical material.
09:43Therefore, we think there is a sweet spot of this technology approach from throughput, from cost, from saving time in
09:54formulation, in clinical phase one and phase two.
09:58And it also supports the need of the pharmaceutical industry to be really fast in man with their drug development
10:06programs.
10:07This is the proof of the pudding for the pharmaceutical industry.
10:11You can test your new drug in a patient.
10:15And if you come quicker to this point, if you come cheaper to this point, this is taking a lot
10:22of risk out of your of your programs, because you should know that only one in 10 programs progresses from
10:29phase one to market.
10:31And even in phase two, it's only one in six and in phase three is one in three.
10:35So if you can make this cheaper, if you can make this quicker, it really supports the need of the
10:41pharmaceutical industry.
10:43So I mentioned this already.
10:45So in our hands, and certainly this depends on the particular problem you have in front of you.
10:52It depends on the particular active pharmaceutical ingredient.
10:55It depends on the particular formulation challenge you have.
11:01But let's say generalized is the following two.
11:09We can save up to 50% of the active pharmaceutical ingredient in our processes.
11:15We can save up to 60% of the time needed for the reformulation that is normally done.
11:21So in the normal procedures, the pharmaceutical industry is doing a first formulation of the tablet for phase one, then
11:30a reformulation for phase two, a reformulation for to be reformulation for phase three.
11:36We think that can be that we can use the very same formulation, the very same production process during the
11:43different clinical phases and therefore save this time and formulation development.
11:48And you can imagine that in a GMP environment that the formulation time of people is quite also an expensive,
11:56an expensive resource.
11:58So therefore, the overall saving is up to 70% in the clinical development.
12:06And certainly we discussed this already in different ways in this Congress.
12:12We think that this is an excellent way forward for digitalizing the whole industry.
12:20The properties of a tablet can be just digitally adjusted.
12:25You just change the file on your computer.
12:27And with that, you can adjust the API dosage, the tap by the tablet volume, the shape, you can twist
12:38the dissolution by using different laser powers and speed.
12:42You can certainly influence the irradiation pattern in your powder bed, how this is exactly done.
12:50And yeah, the batch size is also easily adjusted by just using different sizes of chambers or just using different,
12:58you know, ways of producing the pills.
13:04And therefore, tap by the properties like appearance, content, purity, dissolution and hardness is all easy to adjust in a
13:14file.
13:15And with that, I think this opens up a very different way of thinking about pharmaceutical production.
13:23Today, most pharmaceutical companies are planning a big plant in their headquarters.
13:30They are producing the pills there and they are distributed over the world.
13:35We think with this technology, we can easily change this picture and place the printers in the market with the
13:46market authorizations.
13:47With the development of the markets, we would then scale this with the printers.
13:53That is certainly not applicable today with the throughput we have in hand for the blockbuster indications.
13:59But it's something that, you know, is certainly applicable to smaller indications, oncology indications or orphan indications absolutely also in
14:09the near future.
14:11So our offer then to the market is clearly here that we have a GMP printer or GMP environment with
14:19our formulation expertise at MAC.
14:22The customer can come with the API challenge and we develop in our, we call it one zero met from
14:29one zero met for digital medical medication service, the clinical trial supply.
14:36And later on, also certainly depending on the need of the market, the commercial supply.
14:41And we also foresee that if this technology is accepted by the market has proven that it is can can
14:48really deliver the right to medicine in the right way that then also we sell printers to our customers.
14:57I am stopping here and happy to take questions from the audience.
15:01Thank you very much.
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