Power of Partnership: Finding the Right Provider to Streamline Cell Line Development

"Hello, and welcome to Sartorius' webinar titled Power of Finding the Right Provider to Streamline Cell Line Development, presented by Doctor. Lisa Blaschka, Sandrine Schivalier, and Jerome Thiolier. Please allow me to introduce myself. My name is Elaine Hogan, and I will be your moderator today.

Let me introduce our speakers now.

Lisa Blaschke has been working for Sartorius since twenty seventeen in various roles. She earned her PhD in the field of technical biology from the University of Stuttgart in Germany and started her career as an application specialist for cell line development services at Sartorius. In twenty twenty, Lisa was assigned as a project leader where she led various cell line development projects focused on launching new cell lines and cell culture media products. Since April twenty twenty two, she began driving the strategic development of Sartorius' CHO cell line development portfolio.

Now, Sandrine Schivalier has worked for Sartorius since twenty twenty one as a regional marketing manager in EMEA for the CELLINE Media and Testing Solutions team. She has more than fifteen years experience in the pharma and biotech industries, where she has held various product marketing and business manager roles.

She has a master's degree in cellular and molecular biology and oncology, and an MBA in pharmaceutical management.

And finally, Jerome Thiolier has more than thirty years of pharmaceutical R and D experience in various senior leadership positions, helping to develop first class products for IMDEX, I'm Tix, Sandstock, and Innate Pharma.

He has managed multiple areas of drug development, including CMC, toxicology, PK, drug nonclinical demonstration, translational scientific research, and early phase clinical and regulatory operations. So let's get started. We hope you will enjoy today's webinar on cell line development services at Sartorius. Lisa, please begin when you're ready.

Very good. Thank you very much Elaine for the introduction and welcome everybody also from my side. Very happy today to introduce you to our CHO platform and the services that we can offer to you, in order to reduce the protein biologics development risk.

Good, so the first part will be on the typical protein development pain points.

To highlight then how we can really support here, we will also give an overview over the whole CHO cell line development platform. We also include the cell banking under one umbrella and also the analytical testing. So these will be the topics that I will lead you through now.

So typical challenges of cell line development: You always have to balance of course time to market on the left side and quality mostly on the protein, but also on the cell line of course, and also service quality and so on in your cell line development projects. So within these projects, you will probably see challenges in the identification of the optimal clone, which is very tedious, and you always need to make sure that you end up with a hydroducing clone, which fulfills all the quality needs that you have.

In order to know what you actually achieve as your product, you need to thoroughly characterize your protein and also the cell line itself. And in the end, need to make sure there's a cell line that you have corresponds to all the regulatory requirements FDA and EMA and so on. And you also want to make sure that the cell line not only performs in the small scale and on the lab bench, but also in the large scale.

So these are the typical challenges that our customers face.

And we support our clients by offering the CHO platform.

In the services area, we offer the DNA to cell banks. So that means under one umbrella in one company, we have the cell line development, the protein characterization, this showed cell banking and the biosafety testing. So this is all taken together, all managed by one project manager, one client project manager, who will take care internally that all of these different process steps are aligned in the timeline to ensure that everything goes very smoothly within your project.

And together with these services part of the platform also is the media solution. So we have dedicated media for the cell line, so that also from this aspect everything can go as smooth as possible, in order to be sure that in the end your production process will work out fine.

So where do we do this cell line development? Here we would like to present you a little bit the Center of Excellence for cell line development in Germany. It's in Southern Germany in Ulm and the facility is quite new still. It has been opened in Q1 twenty twenty with six thousand square meters.

We currently have roughly one hundred and thirty five employees there taking care specifically of the cell line development, making sure that around fifty cell line development projects can be performed per year, meaning that we are really dedicated to cell line development here, and we have all the expertise to take any challenge actually from the client and their proteins.

The additional on-site capabilities that we have here is not only COD development for customers, but of course also always improving our services and the platform from a technical perspective, meaning product development.

Then we also have the cell culture media optimization in there on-site and even a pilot batch media manufacturing facility. And by having all of that under one site, we can ensure that the services and products really match together very smoothly.

So based on our CHO services and CHO platform, we have a really solid track record, which would give you the confidence really that you will get a saline and services which cover all your needs. We have performed two forty COD projects already and out of these, the clinical success is really good. So we have started working with clients roughly twelve years ago, ten to twelve years ago. So the first of our clients have now reached market approval. So you see here that two of our clients already have passed the successful market approval and further projects are of course late in this stage and further will come. So all our documentation, the wholesale line has been checked by regulatory agencies in different regions, different countries already.

So here we are really proud that we can support our customers very nicely and provide them everything they need during their drug journey and make sure that they get everything what they need.

The platform is also versatile, so it can be used really for almost every kind of protein. Of course, the typical MUPs, but also fusion proteins, bispecifics and more.

And to show you that in a bit more detail, you can see here the real data. So these are the titers, the outcome of the cell line development projects for the different molecule types. You see the different IgGs, fusion proteins, bispecifics and also enzymes and hormones. And you can see that the titers go up really nicely, not only once over seven grams per liter up to the eight grams per liter, and also not just for standard molecules, but really very nicely distributed over the different molecule types.

So we are just about to launch actually. So we are launching thirty first of October the new timeline, which is DNA to RCB in nine weeks. So this is really competitive.

This is a very quick timeline and we are shortening that pretty a lot, meaning that we can go from the vector cloning and transfection up to the research cell bank within nine weeks.

And after these nine weeks, we have the RCBs and then we can go to the fat batch assessment and make sure that the RCB will be fully characterized. And in the end you get the RCB, the bioreactor run and data and process and also the regulatory relevant documentation.

So it looks like I always have to switch off the laser pointer to go next.

The major components that we have in the COD platform to ensure the success is actually on the left side, the stable host cell line and optimized expression vectors. So meaning we always use the same host cell line and always the same vector.

And this can address really all molecules. This has been optimized for many different molecule types. It's fully compliant with all regulatory agencies and documented, so everything will be there in the documentation.

Together with that, we also have the tailored and scalable media system. This is also optimized for our platform. It's of course chemically defined and animal component free and of course it perfectly supports the growth and tighter production within our cell lines. And on the right side, we also have implemented the process, so the fat batch process typically, which is predefined, meaning that together with the cell line actually, so after nine weeks if you get the research cell bank, you already know which media you can use and which fat batch process and then you're good to go. So that is our benefit of the platform approach. And of course the fat batch process is also easily transferable and scalable, so it's very easy to get started at your facility or at any CMO and in any stage up to the two thousand liter for example typically.

And I already mentioned that our system is regulatory proof, meaning that we know the documentation is well accepted by the regulatory agencies and you can be sure that you have full traceability of the clone history. All the materials and methods are documented. We have a specific single cell cloning validation report, which is also very helpful to prove that the single cell cloning technology is appropriate.

And of course for your dedicated research cell banks, you will get the results including monoclonality assessment.

And yeah, of course it's a full report. And then together with the cell line development, of course, you also need to characterize your protein. So we have the different levels. This is a predefined package that we have here, and then we would sit down together and check for your molecule at which stage you will really need what.

And afterwards, if you have your finally characterized RCB, we can move on to the GMP production of the master cell bank or also the working cell bank. And also here we have all the biosafety tests and so on, to end up with a fully GMP compliant MCP in the end.

On the protein characterization, this is also according to regulations ICH Q6B compliant, and you can divide it here into the physicochemical and structural analysis on the left side, having all the typical assays if you want to characterize the amino acid sequence, the glycosylation profiles, the aggregation and so on.

So this is the left side and then on the right side we also have the activity analysis using bioassays.

We can do basically everything. We have certain platform assays available for different molecule types, the IgG's, mode of actions.

And then we would sit also down there with our scientific experts and check which platform assays might be applicable to your molecule and then also adapt and optimize and develop dedicated assays for your molecule. And these can also cover all the different quality grades from the early development phases up to the validation of the methods for lot release testing, for example.

On the GMP cell banking facility, we have a nice closed system. So meaning that the risk for contamination is really, really low, everything is closed. And we use a lot of our Sartorius equipment, so we have the benefit that we also have that knowledge and expertise under one umbrella. So we can use most importantly actually is the fillet device, which is used to automatically fill the cell suspension into vials, meaning that we can fill more than five hundred vials within just twenty minutes, meaning that the quality consistency of one batch of CELLINK is very high, because the time is so short.

And as I already said, of course we can cover master cell bank and working cell bank and also end of production cell banks. Actually, we can always adapt the different testing that is required depending on the grade or the process step of the cell bank.

Yeah, as we have also the biosafety testing here, this is all managed still by the same client project manager.

And another quality aspect is actually that we have a dedicated qualified person for the CELLINK release. That means that you really have the highest compliance assurance.

So in the end, your MCB will be of high grade here.

And then to characterize the cell banks, we fulfill the ICH Q5A regulations and under that you have the biosafety assays, also the typical ones. So there we have specific predefined packages for FDA for example or for EMA, but we can also accommodate for different other regulations, whatever you would need there.

And the assays are the typical ones. We have the microbiological contaminants, also the viral safety and on the right side the characterization. We do have all the assays for genetic analysis and appearance and identity.

So to sum up, what we can offer as a service provider for cell line development, including the testing and the banking, meaning we can guide clients. So that means we have all the knowledge, we have a very solid track record, so we know what we're doing there. We have done more than two forty CLD projects, so we can ensure that you get everything that you need.

And the dedicated client manager, where we always try to have the same client manager for one client, so that you already have the relationship and so on. You know each other and this person would be the single point of contact for you as a client.

We can predict the performance really well. So the platform approach means that we can easily rely on the system and the protein titers can now go up to the ten grams per liter. We have a standard fat batch process, but also some intensified versions.

It's an integrated platform, so we already know as I said the RCP will be ready together with the media and the process and everything will be regulatory ready.

And ultimately what you need is the speed to clinic or speed to commercial. So of course you want to accelerate and that can be done by, again, using the platform approach. We know that once you have the RCP, it's scalable up to two thousand liter. That saves a lot of time. The DNA to RCP timeline is heavily reduced now with the nine weeks. That is really quick. And then thinking further up to the GMP grade, we can go to the GMP cell bank in less than six months.

And also on the testing side, our platform assay development can be really speedy in six weeks, because we have the platform assays available and can use them and adapt them to your needs and your proteins.

And with that I am at the end of my presentation. Thank you very much for your attention and we will continue now with the interview.

Hello.

Hello, thank you, Lisa. Now, we are on the main event of our webinar. It's always an exciting opportunity to speak with the key opinion leaders in the bioprocessing industry and the people that are supporting the creation of novel therapeutics.

Jerome Cheolier has over thirty years of experience working in pharmaceutical R and D and is currently the president of NoCode M, a consulting boutique in biologics department.

Jerome is here to share insight about his client, Spikeleam, a new biotech startup and how they partnered with Sart 30s to streamline their cell line development for monoclonal antibody therapy targeting COVID-nineteen. Thank you so much, Arium, for joining us today.

Good afternoon and thank you for the invitation. It's always pleasure to share some professional experience.

Good, thank you, Jerome. You already worked with Sartolyse in the past for a cell line development project and you came back to us when your customer Spike Lim was looking for an outside company to develop their cell line. You agreed to share your experience and thank you for that. I have a few questions for you. Are you ready?

Yes.

So first, may I ask you to introduce yourself, please?

Well, you already did some very good descriptions and on LinkedIn you can find my profile.

I stopped working on a day basis three years ago and just consulted to a different company.

I'm a PhD by training and I used to develop a dozen of different monoclonal antibodies in the past.

So it's the reason why some of the people are very happy to work, and I'm very happy to work with Spikeyng on this project.

Great. Can you give us some background about Spikeleam and what you are working to accomplish?

Yeah. First, you have the time, you can have a look on spikeleam dot com, where there are some full descriptions of the company and the project. Spykilm is a new company developing monoclonal antibodies against COVID-nineteen.

These antibodies came from acidic Pasteur and the spiking and the development are financed currently by Truffle Capital. Filter Puritie, who is the president of Truffle, asked me to build together with different people a team to develop this new antibody. And due to the emergency to move as quickly as possible, we hired different senior consultants available at the moment. Kathleen Plato is now the Chief Development Officer of Spiken, driving all the pharma and program operations, and we are working together. And Entrinter is acting CEO. We have currently a team of more or less twelve people working on these very exciting projects since one year and a half.

Then, in fact, we succeeded to bring from the lab, so from the Arium Foster Igo Minkay Lab to the clinics two monoclonal antibodies in less than twelve months between the starting CLD with CELLINK and the first patient in the beginning of August this year.

The goal has been to move as quickly as possible these antibodies, which are a very large spectrum of action against the different COVID variants and which should be in phase two efficacy in immunocompromised patients early next year.

The phase one is currently ongoing and should be added more or less in a few weeks, and we are currently looking to the next step.

Good. That is very interesting, the way you are developing monoclonal antibody against COVID-nineteen in a short time.

Now, can you tell us a little bit about the challenges faced by SPACHIM that required them to decide to work with Sartorius?

In fact, subcontracting and outsourcing activities are key and critical when you do not have a real internal team, when you are working as a virtual company with different people.

And this is really highly challenging.

And past experience in different development is key to succeed when you have the opportunity before to compare different contract result organization and to try to leverage on past success.

Concerning this first step of regulatory development, which is a cell line development, I used to work with CellCase after use for another cell line development in the past two years ago with a great success. And I have been impressed by the results and the program management by this company and the organization.

In the past, I used to work with at least three different cell line development companies, so previously my career. And so I found the balance between technical and cost is for me the best at the moment with CELLINK.

Thank you very much, Arium. This is very nice to hear that, and I'm sure that our colleagues in UMA are happy to hear that.

Let's see now how did Sartor's expertise help Spikelins overcome the obstacles you faced.

So, yeah, the key are in fact timing and reactivity.

Urgency and speed are the masterwork in this COVID-nineteen area, and with Catherine and Katja as a team, we did a very quick survey of different cell line developers and select CELLINK as the best option.

We view, in fact, we selected the acceleration tract because you have a specific acceleration track in order to move forward. But I saw that you provided another more accelerated one. Okay, thank you very much.

And this was very monetary and compatible with the timeline of this development because we are able to take the right decision at the right time and try to do the shortcut during the development.

And for example, we did some batch with CELL pools and we did, in fact, the first CGM path with research cell banks. So we are facing really technical challenge during this development, and we try to share together all the issues and problems and to look at all the different options in this three party collaboration between CELLINK and the CDMO where we are manufacturing the product.

That makes sense.

After cell line development, Certois developed a CELLINK for spiking and providing media for the early phase of the development and the scale up.

Can you tell me what having one provider for all those services and media brings to Spyclim?

Again, in fact, simplification during the process development and manufacturing.

This was really mandatory in this process because we didn't have the time to make some real process development and we used media and fields for the first batches, which have been essential to succeed to, I would say, decent productivity without development steps.

A full development process was impossible due to the timing of development and urgency to move forward to clinics.

That makes sense. Last question, Jerome. Would you recommend Sart 30s services on the way?

Yeah, for sure. And I would like to say that I don't have any compensation to this sharing experience because it doesn't matter. The goal is really to explain how the experience we have together could be shared with other stakeholders.

As mentioned, the development community in the biotech is a small world and share experience and affirmation is really essential to the different stakeholders.

And it's what we did, in fact, with different nonprofit organizations like Frost Bioprinter or Membrane Filters. And all this community, which is relatively small in this world, especially in France, is essential to try to make the right choice at the right moment.

That's great. Thank you so much for joining us today, Jerome. The team at CellCode enjoys working with you and your clients such as Spyclimb. New biotechs like Spyclimb are responsible for significantly impacting the health care industry and leading scientific breakthroughs. And we at Sartorius are honoured that we can play a role in increasing the speed at which this novel therapeutic gets into clinics. Now we have some time to take questions for Jerome and Lisa from the audience. So I will hand over to Elaine.

Yeah, thanks, So like Andre said, now we'll move to the live question and answer from the audience.

Sorry. So if you have a question, please type it in the question box in the control panel. We have already received some questions from the audience.

So our first question, I think this is a question for Jerome. When selecting a cell line development provider, what are the main considerations a virtual biotech must consider compared to more of a traditional biotech?

I would say what I said just before, in fact, is really to have expertise because when you are designing a development, you are more, I would say, a general program manager. You know the people, you know the process, but you don't know really the technical detail and you don't have any teams internally to do the job. So you need to rely on really a network or a different expert.

And then you have the opportunity to work with different people. So Spiking is really a virtual company.

There are several people with different type of experience, but really nobody in the lab except for the biology and pharmacology.

Then it's why it's essential to have some people like you in the cell line development. There are most probably other people in this field, compared to pharma, where in the pharma industry, most of the time, they have their own cell line and their own people working these fields.

Yeah, that makes sense. So it's really expanding capabilities and opening up additional resources to those virtual biotechs.

Okay, so we've received another question as well.

This one, one's for Lisa. How do you ensure scalability for the cell lines produced?

Yes, scalability. So first of all, it's again the platform approach. So we always use the same TODG44 host, we always use the same expression vector, same fat batch process and same media. So as the clones then in the end behave very similarly, it's quite easy if you know that in general the system is scalable, then also this specific clone will be scalable.

The other aspect is that at Sartorius, we have the broad bioprocess background and expertise. So we are manufacturer of EMBER. Everyone knows the EMBER in the field probably.

EMBER fifteen and EMBER two fifty, which covers the small scale, the scale on models from fifteen ml to two fifty. So these are really nice screening tools, which we implement early on in the cell line development or clone screening process, specifically the EMBER fifteen to identify the top clones.

And then we also have the five liter scale. So also there we have the Sartorius equipment of course, using five liter as our final confirmation run. That's how we always call it. And if we know that a cell line works in the five liter bioreactor, then we know that it will also perform well in up to two thousand liter. So for that we have the data.

There is no need to repeat the two thousand liter scale up every time for every single cell line, because as I said, it's the platform approach. So that is basically how we ensure that once we pick a clone for the client, you can be sure that it can be transferred to the large scale as well and also be transferred. That's what I mentioned earlier, that as it is a generic fat batch process first, there might be slight adaptations for a specific clone, but in general it's always the same process and it's easy to transfer, easy to perform by CMOs or any other company.

Great. Thanks, Lisa.

I think this next question is also for you.

Does Sartorius have a drug master file for the production medium that will be shared with the client?

Yes. So as I said, the regulatory aspects are very critical to us. So we want to make sure that the customer doesn't face any issues, neither on the technical side nor on the regulatory side. So as we have the experience of twelve years working with clients, and I said two of our clients have already successfully filed their molecules and got the market approval, we know what we have to do. So everything is there and there is no need, no concerns needed in order to get the cell lines and the whole system into the regulatory process.

Okay, great.

Sorry, Lisa, sticking with you for a sec.

Sartorius is Cell Line Development Services.

Are we also working towards development of a cell and gene therapy requirements and offerings?

So in the CHO business, no.

We are a cell line development excellence center in Ulm, so we definitely have projects ongoing.

However, there yeah, I think I cannot tell too much, but we are CELLINK experts in general and we are working on new products.

With the speed to market being so critical, what early decisions can be made in the process to accelerate timelines?

I can, but actually I think this would also be nice for Jerome to share his experience.

I don't know how do you want to do that? Should I answer first, Jerome, or do you want to?

Yeah, answer first.

Okay. All right, so we have the different tracks.

The acceleration track that Arium mentioned means that we go as fast as possible, meaning that there is not a lot of time actually to discuss before going to the next step, but we want to make sure that even though we are going very fast and in that track the decisions are first in the first instance done by our internal experts and scientists, we still share the data so that there is no risk for the customer. The customer can always analyze the data and they see later on, oh, maybe I would have taken a different clone, we can still go back. But usually there is no difference in the choice.

So that's why customers are really happy with the acceleration track there, because it simply takes the time away for the decision that we need to send over data to the customer, need to find a slot for a call with the client, need to discuss and then customer has to decide. As I said, most of the time the decisions for which clones would go into the next step are anyways the same. And this is one of the successes that we have with the acceleration track, that this is really smooth.

Yes, for sure you have to make some decision, especially in this COVID-nineteen, a very interesting subject because, in fact, we did some shortcut at all the steps comprising at the RCB, where we start the GMP batch without all the stability data.

But it's also why it's good to rely on the very strong and robust process and cell line because with the past experience, we saw that it's not so usual to see non stable cell line, for example, and then you save some weeks and time to move forward.

This is probably more specific for COVID-nineteen because the regulatory authorities accept to have, I would say, for example, a tox with the sample directly not on the clone, but and to have a first GMP with research cell bank and not the master cell bank. But really, yes, it's good also to be sure that we know the system and we can then rely on past experience on this.

Yes, exactly. That's it. And maybe to add in to what Arium just said, the decision points are of course always critical, but if you are so as Sartorius is an integrated service provider and we have all the different steps in house, we can parallelize and we can also as we know the system usually works really well, we can also take a little bit higher risk to move on to the next steps, while doing things in parallel. Just for risk mitigation, you do the stability study for example in parallel, so that you already start the master cell bank generation, although you don't have the stability data yet.

So that is another approach that we always customize together with the customer, depending on the timeline needs. And there we are really flexible, we have some predefined workflows, but we always sit down with the customer and make sure that they always get what they need. Like for example, Jerome said the pool batch, where we produce material based on the pools, this is also something that we very regularly do for customers, because either for talk studies or for analytical development or DSP development, we always make sure that we provide the amount of material that is needed at a specific point.

And on behalf of all of us from Sartorius, thank you for joining us today, and have a great rest of your day. Thank you.

Thank you. Bye.

Bye bye. Thank you. Bye."