Thermo Fisher Scientific Inc. (TMO) Earnings Call Transcript & Summary

Good afternoon, everyone, and a warm welcome to today's webinar. And thank you all for joining us today. My name is Ankita Barve representing Pharma Services Thermo Fisher Scientific. I am from the Business Development team, responsible for CDMO service offerings for clients based in India, Singapore and Australia recently. And I'll be the moderator for today's session. We would have liked to have this webinar in person, but because of the COVID-19 situation, we are happy to address you through this virtual platform. And we hope to see you in person in the near-future. Today's webinar will have 3 sessions from introduction of our overview capabilities to biologics product development and manufacturing, drug substance as well as drug product. Before we start, I would like to introduce Mr. Amit Chopra, Managing Director of Thermo Fisher Scientific India and South Asia. He will now introduce the company's presence in India. So over to you, Mr. Amit.

Good afternoon, and a very warm welcome to all of you to our session today on biologics development. I'm really pleased that you are sparing this time with us. And I want to take you through a very brief overview of Thermo Fisher Scientific and our operations globally and also in India. Thermo Fisher Scientific is a world leader in serving science, and we have more than 90,000 employees around the world, more than 5,700 of whom are engaged in R&D the scientists and engineers. About $1.4 billion of revenue invested in R&D and more than $35 billion in revenue. We are a Fortune 100 company. So really, truly a world leader in serving science. We are very proud of our mission, which provides us the purpose. Our mission is to enable our customers to make the world healthier, cleaner and safer. And this is something that we live everyday day in and day out. This slide reflects the leading brands of the company, and I just want to differentiate and make a distinction between the company and the brands. Our company is Thermo Fisher Scientific. And we have 6 major brands, Thermo Scientific, Applied Biosystems and Invitrogen, which are the innovation and the search-oriented brands; Fisher Scientific, which is a brand for the U.S. and European markets, which is really a fan for choice and convenience; Unity Lab services instruments and enterprise services brand; and take care of course, with the Pharma Services brand, which we acquired a few years ago. We are committed to scientific advancement, and we offer products and solutions that enable customers to push the boundaries of innovation. So the focus of the company is on you to make -- how do we make you successful. And really, it's about having an unmatched portfolio of products and services, industry-leading scale and an unmatched depth of capabilities, which enable us to accelerate -- help you accelerate our innovation and drive your productivity forward. I talked about the unique scale and depth of capabilities, which enables our customers working in health care, in life sciences, in applied markets and in pharma and biotech industries, to really access world-leading technologies and world-leading service levels and services to advance their own businesses and to become more successful. So truly a very unique company with a very broad range of technologies and services. This slide captures a very small part of our portfolio, which is representative of the kinds of technologies that we have. On the left-hand side, you see some specialty diagnostic platforms like immunodiagnostics, clinical diagnostics and transplant diagnostics in our healthcare segment. In the Life Sciences segment, we have clinical oncology platforms based on next-gen sequencing and RT-PCR. We have the Genetic Analysis platforms, mass spectrometry, which is used for proteomics, reproductive health, human identification and so on and so forth. So really truly an unmatched portfolio for Life Sciences. In applied markets, which is in semiconductor, in material sciences, we have electron microscopy, chromatography for pharma and biotech. And then finally, the lab equipment and chemicals in pharma and biotech industries where we have multiple product lines. So really an unsurpassed and evolving portfolio and product mix. In India, we have a large commercial infrastructure and operations, more than 2,300 employees, 900-plus of which are customer-facing. We have multiple locations pretty much all across the country with 17 offices, more than 400 channel partners, multiple distribution centers, application labs, R&D centers, manufacturing sites and custom modern warehouses as well. So truly a very diverse and a very big presence in the country with multiple lines of businesses, local manufacturing, R&D and application capability. So once again, I want to thank you all for spending your time on this session today, and I hope you really enjoy and benefit from the sessions that follow. And appreciate your time very much. Thank you very much.

Thank you very much, Amit, indeed for this brief introduction to our company. I'm hopeful that this would benefit the larger audience today. Let us now move on to our first session for the day. The first session is about CDMO services. So I myself will briefly introduce our integrated services offering. Once again, a warm good afternoon to everyone, and thank you all for joining us today from different locations. I would like to spend the next 15 minutes providing a brief about our CDMO service offerings at large and introduce you to our integrated service offerings. I shall be covering these topics in my presentation: Patheon Pharma Services, who we are and what we offer; addressing customer needs, quality, investments and innovation. As mentioned by Amit, Thermo Fisher Scientific acquired Patheon in 2017. Thermo Fisher Scientific provides industry-leading service solutions for drug development, clinical trial logistics and commercial manufacturing to customers through our Patheon brand referred as Pharma Services Group. We will be speaking more about our Pharma Services in the next slides. With more than 65 locations around the world, we provide integrated end-to-end capabilities across all phases of development, including API, biologics, viral vectors, CGMP plasmids, formulations, clinical trial solutions, logistics services, and commercial manufacturing and packaging. In line with conditions to enable our customers to make the world healthier, cleaner and safer, our Pharma Services Group develops and delivers medicines to market that enable our customers to help more than 1 million patients a day. We offer flexible business models and integrated drug development and clinical services tailored to fit your product journey from development through commercial supply. The pictorial presentation on this slide reflects the depth of the CDMO capabilities. The increased availability of the technologies and the riser biologics has unleashed discovery on unprecedented scale, and to cater to that space, we offer CDMO services for large molecule drug substance and drug products. Our cell and gene therapy capabilities, including viral vectors and plasmid. These capabilities enable us to meet with the increasing demand of new novel medicines. We also cater to the small molecule drug substance and drug product development and manufacturing. Our clinical trial division has clients with the needs of labeling, packaging, distribution and logistics. In a nutshell, we offer industry-leading end-to-end pharma services to simplify the supply chain for our customers. This next slide will give you an idea about the depth and capacities of our different service lines. These numbers are from previous year 2020. We were able to serve 1,200 customers across pharma, biotech, research and clinical lab, consumer, academic and government segments. We understand the unique needs of small companies. And as you can see here, 78% of our clients are new, emerging or mid-sized pharma, biopharma company. We supported over 6,100 clinical trials in 2020. Pharma Services completed 135 CGMP 1 million batches, along with the manufacture and supply of 169 million steriliquid and [ nile virus. ] We also were able to achieve manufacturing of 9.8 billion units of oral solid dosage, including tablets, capsules and softgel. Also, this helped achieve our goal of bringing medicines to market with expertise, flexibility and scale. Let me now take you a little back in time. This slide will provide you an insight as to how we have grown in over the last decade and how we expanded our capacities and capacities across the group. We have tried to present a time frame with a mention of the various acquisitions to date. Thermo Fisher leverages the power of these acquisitions to meet customer needs and offer a unique, fully comprehensive end-to-end solution for our customers. The legacy Patheon business had a strong drug product offering. And with the acquisition of Brammer, we added high point [indiscernible] to the site. Thereafter, in 2014, Patheon merger with Royal DSM added [indiscernible] API site and ground [indiscernible] biologic sites. Acquisition of [indiscernible] added [indiscernible] [ Princeton ] biologics site. We enhanced our trading capabilities with the addition of [indiscernible] site. Acquisition of IDEXX added North American API services with Greenville and Florence West site. Acquisition of Roche site added Florence East API separately, Right after, Thermo Fisher acquired Patheon in August 2017. With the ever-increasing demand of cell and gene therapy space, Acquisition of [ gramma viral ] added wider viral vector services at Alachua, Cambridge and Lexington site. In 2019, acquisition of the GSK site in Cork, Ireland further enhanced API services, including high quadrant compounds. Recently, we had a strategic partnership with CSL to operate the biosite located in Lengnau, Switzerland. And latest to the addition has been the acquisition of Henogen Novasep's viral vector manufacturing business in Belgium. And this is how we have been able to build an industry leader CDMO over the last 10 years. In contribution to the last slide, this slide shows our global presence as of today. Our global network of 65 locations has unlimited access to an integrated network with industry-leading capacities to support customer needs from clinical sales development to commercial manufacturing from drug substance to drug [indiscernible] . As you can see from the slide, we have 6 sites supporting large molecule drug substance, 6 small molecule drug substance supporting sites, 5 sterile fill and finish sites and several [indiscernible] sites in our network. The clinical trial, labeling, packaging and distribution centers are also widely spread across the globe. Our experts around the group have a various of experience and deep technical expertise to solve complex challenges and support your drug development journey. I would now like to summarize our integrated drug substance and drug product offerings with the help of this slide. Our Pharma Services site can develop our source drug substance for large and small molecules, providing viral set of contract development and manufacturing services, design formulations, create clinical supply chain strategies, develop and distribute clinical trial products and flawlessly execute drug product launches for both clinical and commercial. This slide, I would like to highlight that how well positioned we are to maintain supply chain continuity during unforeseen challenges like COVID. We maintain our commitment to our customers as the patient's population they serve. All sites remain operational with no major service disruption to patients receiving the clinical trial medicine. Customers were provided with clear and updated information on the project progress. Also, our TTM, the total transport management services, came in handy for successfully navigating the quarantine zone. We understand the importance of our customers' work and will continue to be a trusted and reliable partner because the world's more stressing diseases don't stop during pandemic and neither do we. [indiscernible] your needs, we analyzed our customer needs and understood that the customers want a partner who can deliver high-quality medicines with assurance, speed and flexibility. And accordingly, we have built strategic pillars to enable us to achieve these customer needs. Our 3 strategic pillars are start your [indiscernible] , integrated offerings and going digital. We are investing and building capacities that not only align with our strategic pillars but also address the value drivers that are most important to our customers. In next slide, I will take you through these. Start Here, Stay Here. We want the customers to start with us in development and stay with us through the entire product life cycle. One of the biggest drivers behind our Start Here, Stay Here strategy is our global network. It enables our customers to deliver medicines to the patients anywhere in the world. To support the Start Here, Stay Here strategy, we have made significant investments in our development and workflow capacities. I will speak about these investments in the next slide. Start Here, Stay Here strategy ensures that customers have an uninterrupted pathway from development through commercialization providing access to specialized technologies and expertise across the Thermo Fisher network. When we talk about our integrated offering, it's about how we work as a team to simplify the experience our customers have with us. Some ways we are able to do this is through our Quick-to-Care program. The program streamlines your drug substance and drug product development, demand planning and clinical and trial supply execution into a single customized solution to simplify your supply chain and accelerate your discovery through clinical development. Recently, we have enhanced our Quick-to-Care program on the basis of the learning and feedback from our customers. Instead of requiring customers to sign up for a whole program at the beginning, we have evolved the process to provide more flexibility to our customers so that they can go at their own pace through this program. This has enabled customers to save as long as [ 40 ] weeks of development time. Another important factor here is a global [indiscernible]. For many of our customers, we are working with them to move all commercial production across multiple sites and medicines under a single [indiscernible] , making it simple for them to continue the relationship with us. This is just an example of how we are simplifying the supply chain, fulfilling our mission and providing incredible value to our customers. Commercial packaging. As another example, we have streamlined our processes and increased speed of delivery for the customers requiring complex packaging concentration, small rounds and quick turnovers for overall solid dosage and sterile dosage. Our focus remains to further simplify the invoicing, proposals and contracting processes so that it's easier for customers to leverage more of our service capabilities. The biggest testimony of our quality is the number of NDA approvals. Pharma Services supported the delivery of 117 NDA approvals for therapeutic drugs from 2010 to 2020. This includes both small and large molecules, and we have supported these NDA at various stages, including early development and clinical trials that we get for many of these molecules. With the help of these digital tools listed on the slide, we have enabled quality and a zero defect mindset. All our sites within the network are U.S. FDA EMA approved apart from various other regulatory organizations. Quantum quality is an important capability within our integrated digital supply that included standardizing our quality process and system across the globe. In 2020, we were focused on the rollout of 3 tools. [indiscernible] a quality management system platforms that have automates quality process, allowing users to document GMP quality topics, perform searches and queries and generate report. Documentum, an electronic document management system that will be used to manage the complete life cycle. Documentum, in compliance with applicable applications, this system safeguards integrity of our data and ensure we are compliant with good documentation practice to meet regulatory standards. Sample manager link, an integrated software platform that uses a laboratory information management systems to manage that workflow. This brings me to the last section of investments and innovation. This brings me to the last section of investments and innovation. With an increasing demand of our services, expertise and capacities, counter commitment to continuously expand our production services. This is why we have been making unprecedented investments in our network of sites and capacities around the world. Our investment is not just about adding capacity. It's about enhancing capacities across our Pharma Services businesses. Some of the examples, and our roadmap are briefed in the next slide. Here on this slide, I would like to highlight the digital supply chain. We are investing to provide customers with fast, real-time access to information to enable an exceptional customer experience. Additionally, in this time of reduced travel and interpersonal content, we are also making it easier for you to actually see our facilities from the inside out through our virtual site tours. If you would like to book a virtual site tour please feel free to contact me. This brings to my last slide for today, which further speaks about the various investments made and the road map. As you can see, we have expansion plans for all the service lines, including biologics. The new bioprocessing collaboration center in Central East uniquely positions Thermo Fisher to bring together industry-leading expertise in single-use technologies and biologic product development. Additionally, we also have strategic partnerships with CSL for the Lengnau, Switzerland site. We also have plans in 2022 for a new site in China, Hangzhou, which would support the biologics development and manufacturing. In terms of sterile, we are increasing our capacity in sterile in several parts of the world to support our customers. We are working arm-in-arm with industry innovators, government agencies and academic institutions to provide scale, flexibility and expertise for the sterile demand. As you can see down the line, in 2022, we have several expansions for sterile: sterile commercial expansion in Greenville for the live virus filling, and live virus filling as well in Singapore and sterile fill/finish in China. Coming to the cell and gene therapy segment. Thermo Fisher certainly expanded its viral vector development and manufacturing capacities -- capabilities of a new site in Lexington, expand sites in Cambridge and Alachua. Additionally, to address the growing demand for cell and gene therapy, in 2020, we announced the construction of a new viral vector manufacturing facility in Plainville, as well as the expansion of our global networking capabilities in [indiscernible] . In early 2021, we announced the acquisition of Henogen, the viral vector manufacturing business of Novasep's based in Belgium. Likewise, we had several investment plans for the API solid dose and clinical drugs over the period of years. This brings me to the end of the presentation. Thank you, and I hope it was helpful for you to understand our capabilities and offerings. So I just wanted to again highlight that we have a question box on the chatbox, which would be visible on your screen. If you have any questions about the services, please feel free to send any questions using the question box or reach out to me directly. Let us now move on to the next session. Our next speaker for today is Ms. Palak Patel. She is one of our global subject matter experts in Cell Line and Cell Culture development. And as mentioned in my presentation, we have 3 commercial biologics [indiscernible] sites built in Australia, [indiscernible] Netherlands and [indiscernible] site. Apart from that, we have operational New Jersey site, which is the center of excellence for the sterile development. In her session, Palak shall talk about the innovative [indiscernible] to activate the cell line and cell culture development. [Operator Instructions] Over to you Palak.

Hi, everyone. I am Palak Patel from PSG division of Thermo Fisher Scientific, and I am very excited to be here today to introduce some of our innovative technologies we have incorporated with global [indiscernible] to achieve an accelerated time line everyone is looking for. So just some background about me, I was born and raised in India, and I came to United States in 2009 for my Bachelor's. I achieved my Bachelor's degree from Cleveland State University, Ohio in 2013. I've been with Thermo Fisher Scientific for about 6 years. Currently, I have a part of scientific and technical affairs team. And in my current role, I support new business opportunities, that provide the technical support to client as well as business development team. My role also focuses on supporting development of new technologies, where [indiscernible] with different teams, different technical SMEs, diverse management and manufacturing scientific team. Prior to joining this role, I was a scientist in cell culture development where I focus on early phase development as well as [indiscernible] clinics for biologics. And I was also [indiscernible] cell and development team where I helped establish the workflows for our new cell and development offering. My areas of expertise includes process scale-up, technical transfers, client-facing and proposal development. So as an introduction of this topic, I would like to talk about the trends we have been seeing in drug development market. So based on drug development market trends, we have seen that previous [indiscernible] biologics market was mainly dominated by IgG1 and IgG4 molecules. But nowadays, we do see that more and more emergence of complex molecules such as bi-specific SD fusion, fragments of [indiscernible] recombinant protein. If you get the trend of complex molecules, there is a need to develop new technologies and new cell lines as well as automated strategies to achieve that speed up that speed that everyone is looking for. Changes in clinical pipeline can also influence changes in business dynamics. Now the existing manufacturing capabilities may not match with the new complex molecules that are in the pipeline currently. And with multiple companies running to the market, time lines are getting shorter and shorter. So there is a need to incorporate innovative technologies, efficient workflows and better strategies to achieve speed to market or to outsource to a CDMO. So as we saw in the previous slide, there are changes that are occurring in drug development market. Even though the trends are changing, our industry still maintains all the biologics pipeline, which is still sustaining approvals, which is ultimately resulting in significant global volumetric need, as can be seen from the left-hand graph. The graph is depicting continued growth in biologics pipeline as well as steady proportion of drug approvals. Although there is a demand for significant volumetric needs, the overall volume needs have significantly gone down due to usage of high-yielding cell lines as well as improved production processes. Before, running 20,000 meter [indiscernible] bioreactor was the standard. But now we are seeing that we are running more and more intermediate scale bioreactor such as 2000 liters as well as 5,000 liters due to improvement in cell lines as well as production processes through incorporation of innovative technologies. So in the next few slides, I would like to introduce you the technologies as well as strategies Thermo Fisher Scientific has adopted to achieve through the clinic and as little as to 2 months from the start of transaction to IND and IMPD filings. To achieve that accelerated time line, we have developed a platform for our cell culture downstream processes as well as [indiscernible]. Along with that, a lot of work was to happen in parallel not just on drug substance side but also on drug product side as well. We are also deploying high-throughput automation technologies such as peaking from [indiscernible] like for single cell owning, high throughput m15 mega bioreactor system, [ TKM clarification ] platform and [ multi-attribute ] methods for CPA analysis. So talking about some of the technologies we have adopted from [indiscernible] combined, microfluidics platform along with optoelectric positioning platform to screen thousands of clones together at once and giving us the reduced time line. We have also incorporated our high throughput AMBR 15 system, which are mini bioreactors for our clone screening process to screen up to 48 clones at once in a [indiscernible] environment. We are also leveraging [indiscernible] liquid handling platforms as well as active systems to optimize all loading conditions. On the analytical side, we are using our multi-attribute method, which is amassed by [indiscernible] that can detect those transmission modifications and giving us also one on glycan as well as charge rating data along with some additional information. So we offer cell and development services. As a CDMO, we need to understand what clients are looking for in the cell line, whether it be high tighters or shorter time lines are strong well documented regulatory package as well as low licensing cost. With this these schools in our mind, we have collaborated with our colleagues from life production division and help established Thermo Fisher platform, [indiscernible] which I'll talk about it in a minute. But the cell line is exhibiting high tighters of between 2 to 5 lines per year. The time line from [indiscernible] is between 4 to 5 lines. The cell line is paired -- the cell line is paired with chemically-defined medium free of any more origin component as well as there is an agreement -- licensing agreement with no milestone or R&D payment. So the cell line, we are offering is for stable expression, the cell line ExpiCHO-S, the ExpiCHO-S cell line, which has been around for quite a bit of time for transient expression. That cell line has been paired with newer vectors, which significantly enhances the expression levels of our protein of interest. So just a little bit of background on our vectors that comes with the kit. The kit is dual vector system kit. The vectors are Freedom, P2 and 2.1 as well as freedom P2P 3.2. The vectors are smaller in size, which allows for more efficient transaction Also, the dual system allows us to adjust durations of heavy gene [indiscernible], allowing us to perform the BOE experimental in transaction. Now that we have talked about our vector system. I also wanted to give you some background on our ExpiCHO-S cell line. So the cell line is derived from our parental CHO-S cell, which has been around a long time and has been -- still used wisely for upstream cell culture processes. Most of the regulatory agencies are familiar with that cell line as well. The characteristics into [indiscernible] are very comparable to parental cell line. Cells do grow up to 20 million and even above 20 million cells per ml with a shorter doubling time of between 18 to 24 hours. We have not a very high specific current productivity as well. In terms of maintaining expression over many passages, we have noted that ExpiCHO-S has to exhibit better stability and expression profile when compared with the parental CHO-S cell line. The graph on the right is giving us a sneak peek of titer AMBR 15 run while during the cell line development stage 4 IgG molecule. As you can see for all the conditions, titer is above 2.5 grams per liter for most of the conditions is around 3 grams per liter . So just some information here on the regulatory support offer along with the cell line development services. As covered in the previous slide, the ExpiCHO-S cell line has to share a [indiscernible] with CHO-S cell line as it is [indiscernible] by supporting the parental CHO-S cell line. So the kit itself includes the ExpiCHO-S cell line. And along with it comes the [indiscernible] documentation which may be required for filing such as information on cell lineage as well as characterization, along with the testing details on AVA as well. Any other data to claim -- any other data to [indiscernible] stability, yields and scalability will also be available once generated. So now I'd like to go over some of the technologies that we are using to achieve that accelerated time lines and to achieve the speed to clinic. One of them is the [indiscernible] that we are using for single cell cloning for our cell and development workforce. It's a very high throughput technology. The system is a combination of OEP technology as well as microfluidics technology. What OEP does is it uses [indiscernible] in that out of chambers. As we can see on the second piece picture, the screen here, the chamber's doors are called Nanopass and that's because that's -- each chamber holds a very small amount of media, which is between 500 [indiscernible] to 1 nanoliter. So a very small amount of -- very small population of data pool is loaded on the beacon and the beacon imports that stable pool into the first [indiscernible] or this chip as we can see. Some of the pages here, which you see on the picture, that's the OEP technology, or OEP line, that's pushing the cells into chamber. Also, what we can beacon is it ensures that each chamber contains only one cell. And if there are more than one cell, the system has the power to take the cells out just to make sure that we do achieve that like high [indiscernible] 80% at the end of the workflow. So each business system holds up to 4 chips and each chip has about 1,715 nano [indiscernible] So when we are running beacon for one time, we get up in the screening power of screening up to 7,000 [indiscernible] in just one shot. This technology also enabled us to do -- to perform the on-chip assay. The assay that does come with the beacon are with the chips, buying [indiscernible] of the molecule and get us through a signal. So as seen on the right-hand side of the picture, as we are growing cells from that one cell into multiple cells over a few days. And when we are performing assay, we do see that source of signal even there is a difference between day 3 and day 4 because we are obtaining more signal or slightly more expressions level on day 4. So here's the side-by-side comparison of our manual traditional workflow versus our beacon SSG cloning. Our traditional workflow is a limiting dilution and the traditional matter to achieve that monoclonal cell line from that polyclonal cell line, that cell population has to go through a series of variations to achieve that monoclonal cell line. And depending on the amount of resources that we are spending, the amount of cells or the clones we can screen is anywhere between 800 to 1,000 clones. We can, on the other side, as we already talked about, there is a [indiscernible] of cleaning up to 7,000 clones at once. Also, it's not labor-intensive as limiting duration as well. Another thing that I wanted to highlight is the limiting dilution to prove that monoclonal concept, each one has to be imaged to ensure that, that is just one cell. And the wall beat it, on the other hand, has a very powerful camera that takes very frequent images. You can [indiscernible] system to take images every 6 hours, every 8 hours to take pictures before lowering the cells also during the contrast state as well as right before the cells are exported into the 96 well site. So it gives a solid proof of [ monoclonality ]. Also another thing to add is we -- in limiting dilution the clones that we are selecting for scale-up is usually solely based on the cell growth and not on productivity assessment. But since beacon has the ability to do on-chip assay, before we select -- we can select the clones based on the productivity for the scale up of as well. So that gives us an initial idea of how our clones will go up later on. So here is -- [indiscernible] quick to clinic offering, the cell development and [indiscernible] clinic offering, where we are starting with the parental unit. So the sequence that we receive from the clients will be outsourced to our gene services division, which will come through expression vector for us. Once expression vector is received from the GI we will perform in-house transaction. And we do the [indiscernible] cell transaction as well and performing multiple transactions. The transactions, once completed, we will do single cell generation, selection at this stage and then single cell generation. Post that stage, we will be performing single-cell cloning, the [indiscernible] platform, as I also highlighted all the features in the previous slides as well of this instrument. The clones exported from the beacon now will be scaled up, and we'll go through the screening process and our end of AMBR 15 high throughput [indiscernible]. Once we -- so just talking about the number of clones. As we just stated, we are screening up to 4x 1,715 clones, which is up to 7,000 clones. By the time clones are exported from the beacon and we are scaling up, that will be 24 clones. So we are narrowing down from 7,000 clones to 24 clones. The AMBR 15 system, we have 48 mini bioreactors, we have 48 AMBR 15 system. So we can also run 48 clones and the AMBR 15 [indiscernible] . From the AMBR 15, based on the results, like titer results as well as product quality assessment from AMBR 15, top 6 clones will be selected. Now those top -- I think this will be created on all top 6 clones. And the RCV from those 6 clones will also be outsourced for safety testing as well. Now those 6 clones, we will take all 6 clones and perform stability assessment on all 6 clones for up to 80 generation. Also, along with stability testing, we will also be running the 6 clones in our [ fed-batch ] bioreactors at [indiscernible] , which is a 12-liter volume and based -- reduced our platform process that we have. And based on the results from the [indiscernible] bioreactors as well as cell line stability results, each clone will be selected. So that's how we are going from 7,000 clones and narrowing down to one of these clones. But to accelerate the time lines, what we are doing is we are running multiple workflows in parallel. As we can see, that once we have RCB banks, we will be running [indiscernible] bioreactors in parallel with safety testing as well. And so that's the cell and development side. But also, in parallel, we will also start our cell culture development workflows. So based on the parameter screen, so once we have those top 6 clones, we will be taking all the top 4 clones, top 4 to 6 clones and doing some initial parameter assessment in AMBR 15 [indiscernible] system. And then results from AMBR 15, we will take those conditions from AMBR 15 and, again, run into the [indiscernible] bioreactor [indiscernible] bioreactors to do some additional process development. So that's how our upstream establishment looked. And once we have a final process, for our cell culture, for confirmation run, then we are also running [indiscernible] at 250-liter or 50-liter bioreactor. And then additionally, we were also running the 2 satellite [indiscernible] bioreactors. So we are transforming our process and the scale at intermediate higher scale along with [indiscernible] scale. So another technology that we are leveraging to achieve those accelerated time lines is our AMBR 15 and AMBR 250 platform. So just sort of a background on AMBRs, they are very high throughput automated bioreactor system consisting of multiple bioreactors between 24 bioreactors or 48 bioreactors. So with that technology, multiple conditions can be screened at once. It also allows for a scalable upstream process development as well, especially for -- especially AMBR 250. So we have been leveraging AMBR 15 for media free screening clone selection as well as process development so forth. But since it's a good screening tool, it's not yet proven to scale that model. So now we are leveraging AMBR 250 bioreactor systems, where we can do a scalable process development as well as also improving a qualified scaled-down model. So we can definitely leverage this and we are leveraging this technology for late-stage programs and also allowing this technology to be a part of our PC work as well. You saw AMBR 250 and Ambr 15 system has definitely allowed us to reduce time lines as well as there are significant raw material savings for clients as well, while we are running [indiscernible] bioreactors, multiple [indiscernible] bioreactors, the media cost goes high. The miniature systems reduces -- removes the entry cost and other raw material costs as well. So for product quality monitoring, PSG has introduced our MAM, which is multi-attribute method [indiscernible] information of product quality from upstream side from cell and development workflows as well as for cell culture workflows. So what MAM is, it's [indiscernible] that uses, reduce mass gap, which can detect translation modifications of the protein. The workflow starts with the start smart digest [indiscernible] kits, which reduces the protein and cuts it at very specific fragments and the protein then turns into a peptide. Now those reduced peptide will go to a de-salting column, which will clean up the samples or fragments. Those clean peptides now will be loaded on the [indiscernible] system, which will separate them, and those separated peptides now will be analyzed through highly sensitive mass pack, which, in this case, is [indiscernible] mass spectrometer. This will generate a lot of data. And to analyze this data, the data will have to go through biopharma finder as well as [indiscernible] software. So the biopharma finder is used for the new molecule or when we are using it for the first time to know about each and every peak and what each peak group presents. Once all the background work is done on biopharma finder for millions of where will be used during subsequent times just for day-to-day analysis of those peptides. So MAM, the information it gives is -- usually, it gives information on the glycan data as well as [ trasvering ] data which can be opting to our [ orthogonal ] method. It also gives us information about oxidation or [indiscernible] as well as low-level imparities. As shown here is the details on the information that MAM gives us. As we can see from the table that MAM gives us much more information compared to our [indiscernible] methods. The only information it does not give us is about aggregate, which at least [indiscernible] for that. For the maybe ones -- because this math is a reduced peptide math, we do get some information about existing [indiscernible] reduction. But if we are running non-reduced peptide mapping, we are gaining much more information for [indiscernible] maybe. But overall, MAM -- the information that MAM gives us is very significant. MAM uses amino acid levels of the molecule while the conventional things that use wireless testing just gives us an oral information of the molecule. The advantages of using MAM that we are seeing as definitely it has helped us lower cost as well as shortening the time lines, as just one instrument is giving us a lot more information compared to running just multiple assays for that information. As I mentioned in the beginning that industry is now moving towards more to a smaller and similar scale, and we are running lesser and lesser scale in steel bioreactors now because of the improvements in cell lines and improvement in our production processes. For single use 2,000 liters are very common at the GMP scale. So now we have 2,000 liter single use, and then there is 20,000 liter on stainless steel bioreactors. So there is a need for an intermediate scale not just -- it's not just if you need more products but also to reduce cost [indiscernible] . And that's where our DynaDrive technology comes in. So we'll introduce DynaDrive at the scale of 50 liter, which can be run for tox patch at 500 liter 1,000 liter as well as 5,000 liters, which can be used for GMP production as well as commercial production. These bioreactors are engineered for robustness as well and they are designed to support modern processes such as high cell-density processes, which requires better P/E ratio or better KLA performance. These bioreactors are engineered for robustness as well and they are designed to support modern processes, such as high cell density processes, which requires better [ PTE ] ratio or better KLA performance. So these systems are able to achieve higher [ PTE ] ratios of up to 80 watts per meter cubed, better turndown ratios as well as better KLA performance which allows for some flexibility. The better turndown ratios allow us to perform N-1 step and same vessel S production steps, which further helps us reduce the cost of goods. And if you are looking for the speed deployment and want to start the journey with us without sacrificing the quality, we do have our [ ExpiCHO Clinic ] platform offering, and we are achieving that write-down of feed as well as [ the rest ]. The timing for offering is less than [ taking much ] from transaction to IND and [ IND to offering ]. And with that, I would like to thank everyone who was able to attend this webinar. And like always, we take pride in our mission of enabling our customers to make the world healthier, cleaner and a safer place. Thank you, everyone.

Thank you very much, Palak. And I believe this was indeed a very informative session for our attendees. I do see a lot of the questions coming in, in the question box. But a little update, that Palak cannot attend the question-and-answer session today because of the time difference. However, we have Mr. Adi Sudiarto, a process engineer from our operation site. He is joining us today for the live question-and-answer session. Thank you very much, Adi, for joining us today.

Thank you, Ankita, and hi, everyone. [indiscernible].

Right. So Adi, I'm seeing a lot of questions coming in, but let me take it in the order they are coming. So the first question is about the platform process. You -- the questions reach like this. You spoke about the platform processes in your Quick to Clinic program. So for your details, what type of platform process were upstream and downstream that you use? Can you give out...

The process that we -- the quick sprint that evolves -- we have standard process, Palak has mentioned in her presentation is the Quick to Clinic program, which is -- uses ExpiCHO-S. In the -- so we have also developed a program like media that can support the growth and also the [ tech mesh ] process that we have in the model. It's like a 14-day [ tech mesh ] process, which basically we have 6 passages of the mixture between 3 to 4 days, and then production phase at 14-day [ fab next ] process. After that, then we go to the downstream process. We are pretty much telling ourselves to separate product using [ filtrations ] and then introduce to the 7 stage of downstream processes, which is a typical sort of length. Well, if you can say that the biologics industrial standard that we can call it, like we have 3 [indiscernible] steps. We have 2-mile reductions, which is using [ bio activations ] of the eye as well as [ filtrations ] on the -- And then we will then keep closing off with ultrafiltration [ filtration ], and then what we call [ the last step of final fill ] or pretty much what we name the products so that, in accordance to [ expect of us ] that is given by [ third client ]. Does that answer the question?

I think so. Thank you so much, Adi. That -- before I take the next question, I would really encourage the audience to post your questions, if any, in the question box or the chat box that you can see. So Adi we have another interesting question. And I think we were not able to touch this in our follow-up presentation, was tech transfer process. So the question reads as, can you please elaborate a little more on the tech transfer process? How are you handling such tech transfer project? I mean what's involved in the manufacturing process to the manufacturing site? [indiscernible] tech transport. Would you be able to take that, Adi?

Yes. So the tech transfer is driven by the global policy from the Patheon Pharmaceutical Group side, and we have our own internal policy. And it's typically around about 16 weeks process where once you have locked in business with us, and we try to start doing the [ therapy fit ] and we get analysis between your processes and then the site process, and -- then we start finding other raw materials, identifying what raw materials that are required to be ordered. With the COVID-19 at the moment, it's actually [ difficult to locate ] raw material [ over time ]. It's been assessed much earlier on before the facility and the [ gas ] analysis. So then we try to find what are the raw materials that you have that will need to be used in the process, then we will [ assess and dispose ] into the [indiscernible] standard for [indiscernible] we need to assess whether are they affected by the COVID-19 materials. Because of -- with the ramp-up of COVID-19 vaccine productions around the world, some of the materials that have very long reach because of the manufacturer, they prioritize the manufacturing of the raw materials to use consumables for production of COVID-19 [ vaccine ]. And then after that, once everything is assessed, we bring in together to what we call a transfer protocol [ or FS ] report. It's basically a process block. And then after that, that process block is used to drive the drafting or the generations of [ batch ] records and across the sites, where whenever that process needs to be. And yes, that's the process. And from that point onwards, it will just be the execution on the manufacturing. They uses -- the manufacturing, you need the best for that tractor that was drafted, which is based on the [ transfer ] report.

Sure. Sure. I think that summarizes it well. One other question is about the type of molecules that we have worked upon. And what scale of bioreactors you can offer for the Phase III and the commercial -- for the commercial scale? So would you like to add...

So sorry, I missed the beginning of it. I've been having technical issues before, but we have 3 sites across -- around the world. We have one in Chatsworth, U.S.A., in America. We have one in [indiscernible] in Europe, and we have one in Brisbane, Australia. So is situated right now in 3 sites. They are situated quite strategically. We have another site area right now that are being built at the moment in [ Magna ] Germany, and there also one in China, but that's probably will be specifically for China market. Other than the 3 [ labs ] that are online right now, we have -- so the capability that we have is up to 2,000 liters. So from anything from 200-liter, 500-liter and 2,000 liter manufacturing scale. And for Brisbane, I can speak that we have 2, 2,000 liters and we have 3 -- actually 2 2,000 liters of Thermo Fisher and then 1 2,000 meters of [indiscernible] bioreactor. So there are 3. And we also have 3 500 liters bioreactor, which is Thermo Fisher. And then the same thing in [indiscernible] running, and there's multiple bioreactors in the site. I think as you engage with us, then we will come into more detail into what is required for the customers.

Right. Right. I think you sum up here. Another part of the question was what type of molecules have you worked upon? So I know most of the time is for IgG1, but we have experienced in other molecules also. So if you would like to speak on that.

Yes. Thanks for reminding me. There's various multiple antibodies. It could be IgG1. There's also some on IgG3, IgG4. We also have a number of [ arrays ] that has some -- an unusual protein, let's say, like an enzyme or then we have also affect what we call fission protein. So fission antibody protein. So those are -- well, that I can speak of from a [ fission ] point of view, but I believe [indiscernible] running and there's also a number of mixed share of those as well that are being across that. I don't really have [ security ] for those sites but I can speak of [ Riffin ] and the mixture of everything. Then we have done before in the last 8 years. And I think [ Riffin ] is also -- I can speak of is that they -- we are heavy experienced team, and then we handle [ antibody 11 ] new product introductions, what we call NPIs. There's basically 11 [ a transfer ] coming from Princeton, New Jersey, the development site [indiscernible] works, or a direct transfers from the clients that work with us or even like if you guys -- the client is actually manufactured at another CMO, then we've also done that before. Okay, but aside from the other CMO, it gets transferred to Princeton, to reassess using our facility [indiscernible].

Right. Right. Thanks, Adi. I see a couple of more questions coming in. But in the interest of time, because we are already running on 5 minutes behind the schedule, for the audience, whatever questions we were not able to take in the question-and-answer session today with Adi, we will make sure that those are attended to you -- those are responded on e-mail. So you can still use the question box. We can have a note of them and come back to you with that. So thank you very much, Adi, for joining us today for the question-and-answer session. And...

Thank you very much.

So with that, let me move on to the next session for today. So the next session would be taken by Ms. Vincenza Pironti. She is a Global Subject Matter Expert for Sterile Drug Products. And she will be taking us through the importance of integrated service offerings, especially for the biologic drug development. Before we begin the session, just a reminder, you can type your questions in the question box, and we should take those questions during the question-and-answer session. So over to you, Vincenza.

Good morning, everyone. My name is Vincenza Pironti, and today, I will talk to you about the capabilities of Thermo Fisher in the development and in the commercial manufacturing on your commercial product. Thanks for the experience leveraging in the last 20 years in this specific field. So looking to the trends in the market, specifically for pharmaceutical companies, what we see is that remember all our injectables, but also biologic compound in the market is increasing constantly. And this is basically driven by the experience and also by the know-how we recently acquired in order to have products stable on the market even for biological compound. It's pretty important and pretty linked to the fact that, when the pharma companies outsource this specific [ servings ], specifically in the field of biological manufacturing, there is the possibility to have [ similar, that can offer as a partner, which can accomplish all the ] life cycle on the biological compound. This means that specifically it is possible to consider the integrated services, which is not just only based on drug substance manufacturing and the product manufacturing, but, as in the case of Thermo Fisher, it is possible to lean this kind of integrated services also in the initial preliminary phases of the development. As Thermo Fisher, there is the possibility to perform also clinical [ lab and pharma partner ], together within the clinical trial supply. And specifically from the formulation point of view, it is possible to develop the formulation and also study together with the pharma partners, which are the best parameters for the manufacturing to have the product stable on the market. So here, if it is possible to think how Thermo Fisher can, let me say, help pharma companies in delivering specifically what are the products, thanks to the fact that, in the case of Thermo Fisher, many sites are present and spread all over the world together, not just with the manufacturing, but also for the distribution in the clinical [ laboratory package ] Here again, just is a dramatic representation on which are the services that Thermo Fisher can offer in the pharmaceutical scene, and which can specifically can be put in the context of biological compound. It is possible to see that in case of Thermo Fisher, there is a bio division that are specifically, it is possible to consider the manufacturing of the drug substance belonging to large molecule classification, as the case of biologics, but there is also the possibility to perform other product development and commercialization. Together, with clearly for the services that I mentioned before of the clinical lab and [ packaging ]. So the last step we are considering, which are the main points to be taken into account when a product should be initially developed and then put on the market. It is important to have the [indiscernible] that can have things from the preliminary phases, as the case of the clinical study, that can follow and fulfill both the environment requirements which are needed in order to submit a fully comprehensive dossier to the authorities. And finally, that can help in the commercialization of the final product. [ What this activity ] has specifically [ services ] that are required in order to follow the [ order of ] life cycle of a product. Starting from the initial formation development with the selection of the final formulation is possible, or at least to accomplish which are the target product profile requirement. It is important to have capabilities where it is possible to reproduce [ immersion pure ] environments [ in batching ] in order to challenge the properties of the product, but in order to find which are the best condition in order to meet -- to which are the final requirement for the stability. In this case, it's possible also to challenge the final process. So to consider as an example, the leads environment, when needed, but also the clinical supply also for animal study in case needed. And it is important to start things from the beginning, the [indiscernible] study development in order to support the means to properly characterize the product since from the preliminary phase of the development. Thanks to all of this knowledge acquired in the preclinical phase, then it is possible to further develop, if needed, the products in order to have consistent formulation, able to be marketed for a reasonable time frame, so with a reasonable shelf life. When the product is commercial, then it is needed to consider many other activities, which are ancillary to the products that are needed in order to have the product fully distributed on the market selected by the pharma companies. So from the initial phase, what's important is to consider which are the main activities linking it to its initial development. It is important to consider which are the phases of development of the products and then identify which are the services needed from the CDMO selected, specifically for the clinical trial [ supply ]. In the case of Thermo Fisher, it is possible to cover almost all the activities starting from the studies -- defining our study, planning and setup, together with the regulatory compliance. And also having place a supply chain intended to fully distribute the products to their clinical site and eventually to consider how their activities, as the case of the preparation of the placebo. But also the supply or the [ comparator ] and other materials needed to perform in the clinical trial. Thanks to a global distribution turnout worldwide, it is possible to reach many sites in many countries. So the global distribution, it is possible for the clinical study and finally also for the commercial. Well, the CDMO is selected one of the first criteria to be taken into account is the quality system. Thanks to a high excellent system from a quality perspective, it is possible to minimize the [ defaults ] during the development, let me say, but also the [ wasting ] of [ higher value ] drug substance as it is on biologics. So one of the first criteria to be taken in consideration from the outsourcing manager is to define which are the quality attributes of the product. And now the [ city that has ] been selected can accomplish and can meet this kind of quality criteria. Once finally defined together with the organization of the outsourcing company, then it is needed to [ have a voucher ] with the aim to reduce as much as possible the division and with principle to have the product right [ that first ] time. And really specifically, it is possible Thermo Fisher thanks corporate procedures but also thanks to the experience acquired in the last 20 years, specifically managing biologics. Thanks to this kind of [ category ], it is possible to build together with the customer plan to prevent deviation, but also procedures which can minimize the [ advent ] of potential deviation of manufacturing process. So let's start the journey of the development of the biological product. What it is important to consider and to have well in mind, during this study of the preformulation of the product, if the pharma companies can deal with just one company, an outsourcing company, it is very important because the main benefit here is that all the knowledge acquired during the initial formation study can be [ leveraged ] in order to help with the last trial, a product which is robust for commercialization. So starting from the initial preformulation, [ one special ability, typically his ] study, together with the [indiscernible] PH, which can maximize the stability of the product, then it should be needed to consider, which is the final strength for the products, so if it is needed to [ consider some factor ] or any other that exceeding that coming in to announce, this will be on the product. And this can be reached through different approach or with onetime parameters in this [ aggressive way ] or otherwise with a design of expedient to unless a tier approach can have part in the filing, which are the parameters that can affect the financial formulation of the drug. 1, 1,200 nanometers and the [indiscernible] are tested. And finally, it was found the best formulation for the products, then it is needed to refund some trials of confirmation. And in this trial, confirmation should be done or in GMP environment in case the laboratory steal a product, otherwise it is possible to perform this kind of confirmation trial directly on a G&P line. Clearly, this is dependent from the amount of drug substance available and it is dependent from the value of the drug substance. In our laboratories, it is possible to consider even a high throughput approach, which can provide the selection on all almost 96 different formulations with small amounts material used. And thanks to this kind of approach, it is possible really to consider different parameters for the stabilization of the product, with the possibility to find and have from 3 to 5 lead candidates to be put on [ subjected ] to define which are the best exhibit for the final formulation. But it is important to consider one biological compound is the product to be developed. And it is important to consider even the specific -- specific peculiarity of the processing tools. What does it mean? Specifically, it's important to consider that the biological compound is more sensitive when compared to a small molecule. So for this reason, it is important to consider here different possibilities with different materials present during the manufacturing. So it is possible to consider the material of the banks once single system are considered, but also the compatibility really affect the [ connectus ]. The presence of a specific mix that can enable a different share test for the material. And finally, we also consider the pumping study of the static pump or different other pumping system in order to define which are the best parameters to accurately dose the product inside of the final primary prevention of [ contaminate ]. Stability can be enhanced, thanks to the initial process. These are often specifically with biologics, biologics which are compound specifically temperate sensitive. So for this reason, sometimes it is needed to consider together with the formation even the process to be considered for the final manufacturing. In this case, it is important to consider which are the final critical quality attributes on the drug to define which is the target shelf life for the product. Sometimes it is not possible to reach 24 months even in life license form. And for this reason, it important to understand even the logistics and supply chain on the product. Starting since from the preliminary phase of the development of the product [ on the physician side ] is pretty important, even considering the instrument which can be deemed as a scale down of the final manufacturing process. So pending the development done, in the same site or in the network where specifically, small scale [indiscernible] are present and which can be simply scaled for commercially distributed. This really [ ups the value ] for the customer because this can minimize the [ trialage ] to be done for the commercial and also enable the customers to define which are the parameters since from the beginning that can affect the final stability of the product. How it is possible. Specifically, in Thermo Fisher and in our development department, it is possible to start with the initial definition of the physical properties of the drug substance, so that's the study the terminal properties of the product, it is possible to define the parameters of the [ supplier's site ], which can finally affect the stability. And thanks to that, it is possible to optimize the duration of each phases of the biocycle. This is really important because thanks to a study made on non-GMP scale, which can define which are the parameters that can affect the movement of the cycle. And it is possible to perform the validation of the cycle. Specifically, this can be done in non-GMP environment, thanks to implementation in the same property for which can withdraw a sample without interrupting the biocycle. So this can be done minimizing the loss in terms of timing, but also in terms of drug substance. So having achieved [ a mode ] that can cover the initial biocycle development up the commercialization is [ really about volume ] because this can minimize the loss of shelf time and also -- basically the scientists dedicated to the initial development have already in mind which are the parameters of the final commercial pretrial. So for this reason, it is possible to see things from the beginning, the parameters that can be easily moved in the commercial. In the development of the biological compound product, analytical activities play a really crucial role, since analytics is used to discriminate different formulation, but also to monitor and check the stability of the product during the stability study. The analytics of the large molecules is not so straightforward. Many methods should be taken into account, specifically [ a solid ] method that can define the stability of the biological compound considering different from the [ status of ] biological compound as the case of decides the aggregation, the possibility of folding of the products. So it is important to have laboratories that can sustain this kind of activities. And it is possible in our development laboratories, which can fall on the activities done in the formulation, thanks to experience in the instrumentation acquired during the last 20 years. Here, just an example of an activity that typically we are required to build together with our customers, a robust development reports that can sustain the submission of [ A to C ]. Specifically, there are many key process parameters that are needed to be defined together with our customer about the process. Some of them are mainly linked clearly toward effective filtration. But also it is important to consider some other requirements, such as the holding time, the exposure to the light and the oxygen. And as mentioned before, it is important to consider even some activities that can be stressful, let me say, for biological compound, and this is of the mixing but also the pumping. Last but not least, clearly, it is important to consider the compatibility study with the materials used. So all the information acquired things from the preliminary phase of the development can be used in order to properly set up all the treatment during the manufacturing of the product. In addition to the previous studies, just to have in mind that all the parameters needed to have a full comprehensive [ industry ] can be built together with the statistical approach of the [ case of ] the design of experiment. And though this activity can start even from the initial non-GMP animal batches. And this can be done clearly under [indiscernible]. After the initial phases of development, then it is important to have in mind how the product can be marketed and which is the sector of the market that -- the sector of the market that -- it is important to go over. This is important from a stability point of view. So if a product can be considered stable in liquid form, then one of the option is to switch the product from liquid to preferred syringes because considering the application of the biological compound, specifically linked to chronic disease, it can be plus in terms of person compliance to have the product in a container that can be directly administered from the [ project ]. So for this reason, after the initial phases of development, typically from the Phase II to the Phase III, it is important to understand if the product then needs, in which from buyers to syringe. In this case, many other options need to be considered in the development of the products such as the compatibility of the final formulation with the syringe container, which means the compatibility with the silicon oil with the tungsten, which are 2 components of this syringe. The silicon oil is used in order to enable the plunger to flow in the barrel of the syringe. The tungsten instead is a metal, a part of the formulation part of the impurity. So the syringe present in a very low level, but that can affect to give it a stability specifically in the use of biological compound. So the switch from buyer to syringes is strictly critical. As in the case of the syringe, clearly we have just 2 components, the glass and the stopper. In study, they can do the syringe. Many other components should be considered. As mentioned, as we need to consider the silicon present in the barrel of the syringe, the metal which is present as included in the syringe due to the process of formation of the syringe, the presence of the metal of the needle and the presence of the plastic and the rubber formula from the needle sheath and the plunger. So for this compatibility study should be done in anticipation, the switch from buyers to syringe in order to demonstrate that this [ kind of switch ] cannot affect the general stability of the product, and the final quality attributes as part to modify, even considering the different kind of packaging. Typically, this kind of which happened during the Phase III, this because specifically during the Phase III, the final formulation has been screened and the process has been developed. And now, this study has been done. So the final dose is fixed. And one important thing is the fact that one: our product is switched into using a syringe, the final strand is well known. So it is clear, which is the final strength of the product. So typically, at the beginning of Phase III, one of the questions that the scientists should cover is which will be the final presentation of the product and when syringe is the final [indiscernible], it is important to consider all the studies that I have presented before about the switch from vials to syringe. Finally, another important parameter to be taken into account to when a biological compound is considered and developed is the compatibility with the material used during manufacturing. Typically, in the case of biologics, the main preference is to deal with the single-use technology. So the plastic material of the back of the tubings and also the sterilization of this kind of material should be taken into account. There are many examples in which the different sterilization approach from the single-use system can make the difference in the stability of biological compounds. Together with the single-use system, clearly each should be considered even better restarting [ those imports ]. So the presence and the possibility to have the system and don't mean stability of the product due to the [ sheeting ] stress and the pumping stress during the dosing of the product. So while all the parameters of the manufacturing products have been well defined, and thanks to the experience that CDMO has acquired during the last year, now it is possible to go to the final validation of the process. It is important to have procedures which can enable or design the scientist is working to have the product on the market made with, let me say, a stage gate approach. So to consider all the parameters that can finally affect the stability of the product and demonstrates that the product is robust and safe enough to be put on the market. This is possible, thanks a robo system and also to procedure that can enabler all the people working on the development of the product to have well in mind the parameters affecting the stability of the product. Still just an example of a case study of an end-to-end service, starting from the early development up to the whole [ med shelf ]. We had, in the past, a product which was developed in our PDF department, which means pharmaceutical development. Services had moved over to our DPF department, which means our product services. Specifically in that case, the possibility to have just one platform [indiscernible] and that project manager with a well-established governance for the communication between the teams belonging to the Thermo Fisher and to the pharma company. So it's possible to have the robust process with a minimal number of trial in order to avoid wasting of drug substance, in order to accomplish all the requirement of the authorities, to have the full comprehensive dossier with a rational approach on the trials to be undertaken. So thanks to this kind of structure of the technology transfer, it was to have the product development with the immediate amount of clients. The product was approved in just 6 months after the [ handy ] submission and launched in 24 hours after the approval. This clearly was possible thanks to a clear communication between the customer and Thermo Fisher. And thanks to the possibility to have a partnership established since from the beginning in order to make [indiscernible] and adding, its access history and track record. So which are the parameters that can make successful an interaction between a CDMO and a pharma company? Specifically, it is important to understand which is the final target of the product. While all the attributes are well clearly in mind, then it is important to have a certain flexibility in the manufacturing possibilities, and this can happen when inside a CDMO network are present in the development, but also manufacturing capabilities. Considering which are the mainframe of biologics. And really important is to understand which is the trend on the market, so try to anticipate which can be the final target on the market and the case of the switch from vials to syringe. So start these kind of studies from the preliminary phase without waiting too much in order to have all of the study in place with the selection of the containers and also the manufacturing parameters. It is important to understand which is the product formulation, which are the parameters. And if it is needed to have the [indiscernible] in order to meet the final target of the product. And it is important to have an integrated solution, which can link each phases of the product, starting from the preliminary development of the product, with the clinical labeling and packaging distribution, with the final validation in the commercial scale for the product. When all these points are together and mixed together, typically, the historical success can be possible, making reality the development even on challenging products as the case of biologics. Thanks, all, and I'm here for your questions.

Thank you so much, Vincenza, for this wonderful presentation, and I'm sure the audience must have benefited a lot from your session. We now can move towards the question-and-answer session. I see a couple of questions coming in. And before I start picking up the questions, I would again encourage the audience to type your questions in the chat box so that we can take it either in the live question-and-answer session or we can reply back to you on e-mail. I also wanted to acknowledge one of the attendees highlighted that he was facing some volume problem. And we had, in the beginning itself, adjusted the volume to 50% increase. So I'm sure the session was profiting [ audible ]. So moving on to the question-and-answer session, Vincenza. I see the first question coming up is on the slide, which you represented for the Phase III, what type of presentation should we have? The question is, are there any risks involved if we wait in Phase III to switch to PFS, especially for the biologics product? And if there are any risks, could you elaborate?

Yes, absolutely. Thank you, Ankita. So the main risk is linked to the stability of the final drug product because, as mentioned, there are some components of the syringe that can affect the final stability of the drug product, as the case of the interaction with the silicon oil and the tungsten. So for this reasoning, it is important to well understand which are the parameters that can affect the stability of product since from the beginning. And in case the final target for the profile we require is syringe as final container, then it is important to start this kind of investigation, even in non-GMP environment, considering a Phase II clinical study in order to prevent any potential -- the addition of the final inject product and foresee which will be the final aspect of the syringe. So to define the material on the syringe, and qualities needed to have the final product finally developed and put on the market.

Yes. Absolutely. Absolutely. Clearly makes sense. I hope that answers the question [ you asked ]. The next question which I'm taking is it says like from your presentation, it appears that the product profile could influence the development of the biologics products. And if that is correct, could you detail as to how the target product profile can influence the department?

Absolutely. It is important to understand which is the target concentration of the drug product because in case of a concentrated product, it is important to understand, which is the final [ submission ] and what's the sustainability. So considering where this parameter is, it is important to define which is the final indication of the product and the final route of administration because this can make a difference in the overall development stages of a biological product.

I have a couple of more questions. The next one is a little generic one. And it says that is there any development protocol which you have seen has water bonds, specifically for the biologic products? And if yes, I mean could you speak more about it? The development protocol. That what's the question. It's a very generic one, but if you want to take it.

Yes. Based on the final target product profile, it is possible to elaborate together with the customer a list or studies to be submitted to the final drug product. It is important to have clearly in mind which are the properties of the drug product. So as example, the sensitivity to share stress or bumping study and include all this studies inside the protocol. We have standard approach that we can follow and suggest to our customers and they [ cite ] together before the studies are required and which are needed to be [ harbored ] in order comprehensively describe the stability of final drug product.

Absolutely. I'll take one more question in terms of -- just in the interest of time. And the final question is again, more on the capacity front. The attendee is asking that what kind of experience that we have? What number of projects? And what fill volume and everything have we catered to for the PFS and the cartridges kind of thing? I mean what experience does all 3 sites of us have it? Or if you could speak more on that.

So we have capability to fill syringes in all the 3 sites, currently established for development and commercial, which are Greenville, Monza and Sarentino, specifically Monza and Sarentino are both in Italy. And Greenville is based in North Carola, U.S. In order to make it possible to fill syringes and cartridges, Monza is very recognized internally as the center of excellence for the specific format, having more experienced since the first line based on syringes was installed in 2014. So almost 7 years from now. We have multiple products already in the market, with differences in volumes and different sizes. We can start from 0.5 ml PFS up to 20 ml PFS or cartridges. So we are flexible in our formats, and we have acquired really good experience, even for non standard syringes based on plastics. So there is really a huge possibility. And typically, we discuss with our customers, which is the best choice for their product. And they run back, they find together which is the best strategy, even from ceiling volume and size of the syringe.

Right. Right. Even though I said that this is the last question, Vincenza, I just have one more question. I mean, again, it's a generic one and I thought it should be addressed for the entire attendees today. So the question is -- the attendee is asking for you for [ in our size ] is adding more -- is stainless steel more preferred? Or we more kind of use a disposable kind of commodity? So I know that question keeps coming in, so I thought let's address it here and now.

Yes. So first of all, we need to understand which are the properties of the product. If there are any incompatibilities, then this can be established and, in some day, preliminary phase of the development of the drug product. In case of any specific incompatibility, we can select the proper materials to be a contact with the direct product. We are flexible on that. We have the possibility to offer disposable lines. So most of them are made of plastic or silicon. Otherwise, it is possible. In case of specific incompatibility of the drug substance with plastics or silicon, it is possible to propose [indiscernible]

All right. All right. I think that sums it all. Thank you, Vincenza, for answering those questions. And with this, I think we come to the end of today's webinar. And let me again thank all the attendees for joining us today. You have been such a wonderful audience, and I hope today's webinar has helped you understand biologic development and our integrated service offering. The questions which we could not attend in the live Q&A session, we will try that we respond to you as soon as possible via e-mail. And until then, take care. Have a wonderful evening, and thank you again for joining us today.