BIOTHERAPEUTICS DEVELOPABILITY
AND RISK MITIGATION
BIOTHERAPEUTICS DEVELOPABILITY
AND RISK MITIGATION
Pierre-Mehdi Hammoudi
17 rue Crépet
69007 Lyon
+33 (0)4 78 02 39 89
pierre-mehdi.hammoudi@mabdesign.fr
www.mabdesign.fr
BIOPC2024
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Currently Global Vaccine MSAT Head at Sanofi, Cécile Gény brings over two decades of expertise in industrial process development within the pharmaceutical industry. With a strong foundation in biotech processes from development to registration, she has led biotech process development from small scale to industrial scale, as well as large-scale manufacturing operations and quality control labs across multiple countries within Sanofi. Additionally, Cécile has significant experience in gene therapy, having established viral process manufacturing platforms for gene therapies targeting rare diseases.
Macrophages fulfill critical functions in immune and tissue homeostasis and are key players in immune health. Their sensory functions, tissue cleaning and effective communication within tissue environment via the release of a plethora of molecules coordinate the control of inflammation, stem cell recruitment and tissue regeneration, collectively driving resolution of inflammation. Impaired resolution of inflammation, is an emerging hallmark in chronic inflammatory immune and degenerative diseases, representing an attractive target for new disease modifying therapies.
We and others have discovered that secretomes have therapeutic activities exceeding that of cells, which led us to develop two clinical ready approaches, harnessing resolution associated macrophages secretomes. Our GMP-certified platform Cell●Secret●Service has been successfully tested transforming resolution associated secretome drugs from of human blood leucocytes.
Our first platform candidate derived from pooled healthy blood monocyte-derived resolution-type macrophages, RESOLVIX®, has demonstrated disease modifying activity in established preclinical sclerosing models in a dose dependent manner. Single intra-venous injections demonstrated immediate and durable control of inflammatory effectors, reengagement of resolution as attested by regaining of macrophages phagocytic activities and most importantly the reversal of established skin fibrosis. Fibrolytic activities were confirmed on patient’s fibroblast samples, further supporting a clinical evaluation in patients with diffuse cutaneous Systemic Sclerosis (dcSSc).
Recently we also confirmed that therapeutically active secretomes, can be obtained from patients own cells. In animals with established collagen-induced arthritis, receiving clinical relevant standard of care treatments, the ex vivo generated resolution associated secretome showed similar therapeutic activity in controlling arthritis, as a secretome from healthy animals. Potency testing on Rheumatoid Arthritis (RA) patients samples confirmed this observation. With our pre-clinical safety data from large animals, established regulatory drug release testing, these new sectreome therapies will be evaluated in clinical proof of concepts of therapy refractory dcSSc and RA, respectively, starting 2025.
If safety and the compelling efficacy is confirmed, our a next generation secretomes might become a new generation of truly disease modifying biological drug candidates.
Sylvain Perruche, PhD (Founder and CEO of MED’INN’PHARMA) is an immunologist at INSERM with more than 20 years of research experiences that led to the discoveries currently under development at MED’INN’PHARMA. Until recently he led the Team Autoimmunity-Transplantation-Inflammation team at RIGHT institute (UMR1098 INSERM/EFS/University of BFC) and obtained his HDR ‘habilitation de recherche’ in 2011. He has published numerous publications showcasing his research in immunology and inflammation resolution (h-index= 17 (October 2020, 78 publications from Web of Science Core Collection), 47 publications in PubMed).
Developability assessment is crucial in the pharmaceutical industry to proactively identify and mitigate risks for drug candidates. Without a thorough understanding of these risks, entire biotherapeutic programs could be jeopardized. Standard monoclonal antibody (mAb) centric concepts may not fully encompass the critical parameters required for next-generation biotherapeutics. This presentation will highlight anticipated risks associated with next-generation biotherapeutics, alongside mitigation strategies, illustrated through recent Novartis case studies. Additionally, approaches to manage the escalating resource demands for risk detection will be explored.
Senior principal scientist for NBEs at the Biologics Research Center Novartis. This role involves the assessment and coordination of the adoption of strategic and innovative concepts in the analytical domain for novel and complex Biologics entities. It emphasizes the evaluation of Biologics molecules’ liabilities and their developability assessment to ensure a streamlined and effective development process. Prior industry experience includes Project management for Biosimilar projects at Solvias AG, Switzerland, and Scientific role in Antibody Engineering and Analytics departments at Glenmark SA, Switzerland. Holds a doctorate in Structural Biology from Biozentrum Basel, Switzerland.
Camelid derived VHH domains are versatile building blocks for the construction of multispecific antibody architectures. In this talk, I will present examples on how VHHs can be exploited for the activation of immune cell subsets by engineering efficient effector cell engager as well as by constructing cytokine mimetics. However, one obstacle relies in the foreign nature of camelid derived VHHs with respect to biomedical applications. We have recently described a novel library approach for the isolation of fully humanized VHHs following camelid immunization. I will describe this process that is based on engrafting the immunized CDR3 repertoire onto humanized backbone libraries followed by yeast surface display.
Stefan works as Senior Director at Merck Healthcare KGaA (EMD Serono), Germany, where he heads Global Antibody Discovery and Protein Engineering (ADPE). He holds a PhD in chemistry as well as a habilitation in biochemistry. In addition, he is Professor of Biomolecular Immunotherapy at Technical University of Darmstadt.
VMF (Vibro® Membrane Filtration) is a novel technology for micro- & ultrafiltration steps in all kinds of upstream and downstream bioprocesses for API/enzyme/mRNA/vaccine processes, precision fermentation, water treatment and bioenergy. Its design, combining 2 patented technologies developed and owned by SANI Membranes, the Free-Flow-Plate™ and Vibro® technologies, will be described. Being capable of running at extremely low and uniform Trans Membrane Pressure (TMP), and keeping the membrane open, VMF is a true game-changer offering new application opportunities and higher performance compared to other currently available technologies. Being fully scalable, VMF is an ideal technology for all bioprocesses and process intensification. In upstream, VMF can be used as cell retention/clarification device, and in downstream, for UF-filtration with cutoffs ranging from 1 to 800 kDa. Due to its unique design, cells will interact with a very gentle environment, enabling higher cell concentrations and product transmission to significantly increase upstream process yield. Additionally, bioprocesses’ yield can be optimized using VMF, as it is fully drainable, even at high concentration and viscosity. Higher performance in all kinds of biomanufacturing processes and many other benefits of using VMF such as low CAPEX, up to 90% lower energy consumption and sustainability will be presented.
Figure 1: Illustration of the novel and sustainable Vibro® technology to support new opportunities in all kinds of bioprocesses within pharmaceutical, food, precision fermentation, water and bioenergy processes.
Jarno Robin serves as Pharma Business Development Director at SANI Membranes, where he is responsible for the development of Vibro Membrane Filtration (VMF) Technology in pharmaceutical applications. Jarno Robin has headed the product launch of SANI Membranes new filtration units for sterile applications, enabling next level of process intensification with results not possible with any other filtration technology. He has a long a career in management positions within upstream and downstream processing from Novo Nordisk, Sanofi and LEO Pharma.
PATs solutions have been implemented to understand the bioprocesses with a goal to control the quality of the final product. The main goal is to decrease time & cost, and to increase the yield of bioproduction to improve access to ATMP (Advanced Therapy Medicinal Products). GenSensor aims to implement a biological PAT approach from R&D phases to industrialization at the service of bioprocesses 4.0. We intend to develop a compact and a fully automated system that measures in real time the expression level of biomarkers throughout the bioprocess in a rapid and reproducible manner while excluding biological variability.
For the first time, we present the GenSampler; an automated system that enables a gentle sequential sampling of drug-producing cells followed by cell lysis for RNA extraction: one step closer for a better control of upstream bioprocesses.
PhD in Health Sciences with postdoctoral experience in Microfluidic field and Stem cell bioproduction. I’ve joined GenSensor as “Field Application Scientist”. Our aim? Improving access to ATMP (Advanced Therapy Medicinal Products) for the benefit of patients. We develop innovative biological PAT approach from R&D to commercial production in a 4.0 bioprocesses industry. My mission is to work on collaborative projects and to provide a worldwide customer support and scientific expertise to meet their needs, given the multicultural background from which I come.
Automation has been implemented in vaccine bioprocess development to screen larger panel of parameters and gain time at each step of production and analysis. For further integration, the Bioprocess and Analytical Sciences departments embarked on a journey to assess a workflow from sample generation to sample analysis. The comprehensive mapping of existing workflows unveiled opportunities for enhancement, particularly on three pivotal steps: sample preparation and aliquoting for analytical testing, analysis, and digital interfaces.
Leveraging on advanced robotics, sample preparation was automated in standardized containers, encompassing distribution, labeling, tube capping/decapping, and other repetitive and low value-added tasks when performed manually. For analytics, fully automated systems were implemented, as illustrated by the 384-ELISA platform coupled with advanced analytical modules and software. The implementation of a Laboratory Information Management System (LIMS) served as the cornerstone for digital data management and transfer, enabling traceability and seamless communication between laboratories, analytical systems, and bioprocess scientists.
Through automation and digitalization, we have not only optimized our workflow but also laid the foundation for future advancements in bioprocess development. Thanks to this automation and digitalization initiative, we increased analytical pace and throughput and generated additional data, thus contributing to generating more data which is necessary to build relevant bioprocess models as well as digital twins.
This work was funded by Sanofi.
All authors are Sanofi employees and may hold shares in the company.
Automation has been implemented in vaccine bioprocess development to screen larger panel of parameters and gain time at each step of production and analysis. For further integration, the Bioprocess and Analytical Sciences departments embarked on a journey to assess a workflow from sample generation to sample analysis. The comprehensive mapping of existing workflows unveiled opportunities for enhancement, particularly on three pivotal steps: sample preparation and aliquoting for analytical testing, analysis, and digital interfaces.
Leveraging on advanced robotics, sample preparation was automated in standardized containers, encompassing distribution, labeling, tube capping/decapping, and other repetitive and low value-added tasks when performed manually. For analytics, fully automated systems were implemented, as illustrated by the 384-ELISA platform coupled with advanced analytical modules and software. The implementation of a Laboratory Information Management System (LIMS) served as the cornerstone for digital data management and transfer, enabling traceability and seamless communication between laboratories, analytical systems, and bioprocess scientists.
Through automation and digitalization, we have not only optimized our workflow but also laid the foundation for future advancements in bioprocess development. Thanks to this automation and digitalization initiative, we increased analytical pace and throughput and generated additional data, thus contributing to generating more data which is necessary to build relevant bioprocess models as well as digital twins.
This work was funded by Sanofi.
All authors are Sanofi employees and may hold shares in the company.
I joined Sanofi in 2004 for an internship in global clinical immunology to transfer methods from Val de Reuil to Swiftwater site (6months on both site).
In 2005, back in France I obtained my first job in Marcy l’Etoile site as technician in Analytical sciences department in virology unit working on SRID and virus titration methods for several projects.
I graduated in 2014 master’s degree in Genetic and cell biology, infectiology specialty. It was my first experience in bioprocess as I did my master’s degree internship in bioprocess R&D lab in Marcy l’Etoile.
From 2014 to 2023 I’ve worked as associate scientist in the Analytical sciences department working on several projects and methods/equipment:
Major improvements to IC-BEVS remain limited by poor understanding of the underlying biological mechanisms driving host cell response to baculovirus infection and efficient expression of recombinant genes. Here, single-cell RNA-sequencing (scRNA-seq) of baculovirus-infected insect (Sf9 and High Five) cells producing AAV (as gene therapy vector) or influenza VLPs (as vaccine candidate) was implemented for the first time to shed some light into these mechanisms, providing key information for rational design of genetic engineering strategies to improve product titers and/or quality.
Using scRNA-seq an increase in cell heterogeneity as infection progresses was shown in both insect cell lines, as cells shifted towards clusters with higher expression of viral genes. Additionally, infected cells revealed varying transgene levels, highlighting limitations in recombinant gene expression using viral expression systems. Gene expression changes throughout infection and between different cell states were revealed using trajectory- and cluster-based approaches. Identified genes were associated to biological processes such as cell cycle and metabolic pathways, showing great promise to identify targets for assisting genetic and metabolic engineering in insect cells.
The improved understanding of biological mechanisms in various insect cell-based biopharmaceutical production processes holds great potential for advancing this field and promoting the use of transcriptomics in IC-BEVS.
I am the head of the Cell-based Vaccines Development Lab (since 2019) and Coordinator of Late-Stage R&D Bioproduction Unit (since 2021) at iBET. In this role, I coordinate and/or manage multiple national and EU funded projects as well as R&D service driven projects focused on vaccines and viral vectors production. My current research is driven by the aim to develop novel complex biopharmaceuticals with impact in Human and Animal Health.
I hold an BSc in Chemical Engineering from FCT-UNL in Portugal, and a PhD in Engineering and Technology Sciences, Systems Biology from ITQB NOVA in Portugal.
It is important for a CDMO to offer its clients a guarantee of manufacturing capacity that ensures the safe, timely and cost-effective availability of medicines while complying with applicable regulations. This is why EFS is committed to providing a fit-for-purpose and innovative approach to meet these challenges.
One of the bottlenecks for cell-based drug product release is the performance of the conventional in vitro and in vivo viral assays on Master Cell and/or unprocessed bulk of ATMPs which requests long timing and offers at the end an incomplete viral safety picture that needs to be completed by a viral risk assessment based on extended knowledge of their own and supplied materials.
As a CRO partner of CDMOs and via its IDTECT platform technology, PathoQuest can offer GMP and validated NGS assays suitable for replacing classical assays. Moreover, PathoQuest helps the manufacturer to support and facilitate their virus safety risk assessment by bringing agnostic IDTECT capacity to turn out the risk from partially theoretical to broaden proven data in accordance with ICH Q5A (R2). Using the IDTECT Agnostic Transcriptome Assay as an example, EFS brings here a return of CDMO experience using PathoQuest platform in the context of their CDMO service.
Delphine Gricourt is Marketing Director at PathoQuest, a CRO specializing in next-generation sequencing (NGS)-based solutions for biosafety testing. With over 15 years of experience in the life sciences and biotechnology industries, she has held various leadership roles in global marketing and communications, in the pharmaceutical industry (Novartis) and outsourcing services (Eurofins CDMO).
It is important for a CDMO to offer its clients a guarantee of manufacturing capacity that ensures the safe, timely and cost-effective availability of medicines while complying with applicable regulations. This is why EFS is committed to providing a fit-for-purpose and innovative approach to meet these challenges.
One of the bottlenecks for cell-based drug product release is the performance of the conventional in vitro and in vivo viral assays on Master Cell and/or unprocessed bulk of ATMPs which requests long timing and offers at the end an incomplete viral safety picture that needs to be completed by a viral risk assessment based on extended knowledge of their own and supplied materials.
As a CRO partner of CDMOs and via its IDTECT platform technology, PathoQuest can offer GMP and validated NGS assays suitable for replacing classical assays. Moreover, PathoQuest helps the manufacturer to support and facilitate their virus safety risk assessment by bringing agnostic IDTECT capacity to turn out the risk from partially theoretical to broaden proven data in accordance with ICH Q5A (R2). Using the IDTECT Agnostic Transcriptome Assay as an example, EFS brings here a return of CDMO experience using PathoQuest platform in the context of their CDMO service.
Experienced Quality Control Manager with over 16 years of expertise in the field of biopharmaceutical. Pauline Souêtre began her career at Bio-Rad laboratories, then specializing in vaccine quality control, where she honed her skills for eight years before transitioning to Advanced Therapy Medicinal Products (ATMP) quality control in Établissement Français du Sang (EFS) in 2016. Pauline’s extensive experience in selection, implementation and validation of molecular and cellular assays for bank characterisation enables to define innovative testing strategy in terms of safety and efficacy, to answer the regulatory requirements for clinical trials in the field of cell therapy.
In recent years, mRNA technology has garnered significant attention from pharmaceutical companies, particularly following the approval of COVID-19 vaccines. This complex modality requires sophisticated analytical techniques for thorough characterization. Our presentation will delve into the analysis of critical quality attributes of therapeutic mRNA such as 5’-capping and 3’-poly(A) tail. We will discuss how both 5’-capping and 3’-poly(A) tail were quantified using LC/MS, utilizing a unified sample preparation approach that addresses the typical scarcity of available samples. This streamlined preparation method also facilitates the analysis of residual nucleotides and aids in characterizing the lipids that make up the lipid nanoparticles in drug products.
Arnaud Delobel is the R&D and Innovation Director at Quality Assistance, with expertise in analytical sciences spanning across all types of therapeutic modalities. He is a recognized expert in the ‘MAB Working Party’ at the European Directorate for the Quality of Medicines (EDQM) in Strasbourg. Additionally, he contributes to academic discourse through lectures at the University of Strasbourg.
Arnaud graduated from ECPM Strasbourg, focusing his PhD on the mass spectrometry of proteins and peptides at the CNRS in Gif-sur-Yvette, France. He then completed a post-doctoral fellowship in Liège, Belgium, centered on proteomics. Joining Quality Assistance in 2006, Arnaud has climbed the ranks, holding various roles before assuming his current position as R&D and Innovation Director in 2016.
Bérengère got a Master of Science in molecular biology and microbiology, followed by a Master’s degree in business. After 5 years’ experience in the transplantation field, she joined ThermoFisher as an application engineer for the BioProduction market for 11 years.
In 2021 she joined Repligen’s analytical teams as European application support for SoloVPE, FlowVPX and RPM users.
Currently Bioprocesses development scientist at Sanofi, he’s in charge of developing purification processes for recombinant protein involved in new vaccines.
Alan Deduyer trained as a Biotechnology engineer has specialized in bioprocess development (purification and E. coli fermentation) from the beginning of his career at Sanofi in 2021.
Manufacturability is the design and the intensification of a production process to facilitate operations and decrease the overall costs. This is thus an essential step for a biotherapeutics on its way to market. Although the development pace of biologics has remarkably increased in the recent past to reach early clinical development phases, large-scale manufacturability often remains a concern of late program phases.
Through a few examples, we will illustrate why we think manufacturability should drive process development and how this approach allows us to avoid technical hurdles, increase efficiency and robustness while decreasing costs.
Attracted since always by biology and life sciences and developing further interest in technological domains, I naturally oriented my carrier in the Biotechnology industry. For now more than 20 years, I have worked in different biopharma companies for the development of human health ingredients, then I was involved in bacterial vaccines process improvement and lately antibodies and ADC GMP manufacturing. During these diverse experiences, I contributed to put in place innovative, efficient and cost-effective processes meeting the highest quality standards with the aim of producing molecules enhancing human life.
Manufacturability is the design and the intensification of a production process to facilitate operations and decrease the overall costs. This is thus an essential step for a biotherapeutics on its way to market. Although the development pace of biologics has remarkably increased in the recent past to reach early clinical development phases, large-scale manufacturability often remains a concern of late program phases.
Through a few examples, we will illustrate why we think manufacturability should drive process development and how this approach allows us to avoid technical hurdles, increase efficiency and robustness while decreasing costs.
Following my PhD focused on protein-RNA interactions and ribosome biogenesis, I spent two years as a Postdoctoral Researcher in human genetics before joining GTP Technology as Chief Scientific Officer. For the past 22 years, I have been deeply involved in designing and optimizing solutions for the expression and purification of recombinant proteins in both mammalian and microbial hosts. I participated in the development of dozens of processes for a variety of biotherapeutics including monoclonal antibodies and challenging proteins.
Bioprocessing aids such as surfactants play a key role in maximising the output of production cell lines, alongside their importance in producing and maintaining a safe, efficacious, and high purity drug substance throughout the downstream process. In this talk we shall give a snapshot of how Croda Pharma has developed and optimised specific surfactants for upstream processing to insure consistency in performance and quality. In downstream we will demonstrate how surfactants can be used for processes such as viral inactivation, cell lysis, antibody stability and purification. For final fill we shall show how Croda’s Super Refined excipients can improve the long-term stability of biotherapeutics. Learn more about the cutting-edge advancements that set Croda Pharma apart as an integral supplier to the biopharmaceutical industry, helping us to empower biologics delivery.
James has over 15 years’ experience focusing on the creation and optimisation of detergents for the formulation and bioprocessing sectors, predominantly for the pharmaceutical sector. Working at Croda he has focused on utilising Croda Pharma’s range of excipients bioprocessing aids used in pharmaceutical production to improves processing performance and long-term formulation stability. James has a particular interest on the role detergents in protein-protein and protein surface interactions along with building understanding on the role of excipient type and quality on the stability in both small and large drug molecule formulations.
Cell density is one of the most important, if not the most important KPI in cell culture and fermentation processes. There are many traditional methods to measure cell density, but these are mainly off-line methods. These have many disadvantages, the main ones being the low resolution and the cumbersome integration of the data into existing systems.
Inline measurements with sensors installed in the reactor are now state-of-the-art and are replacing these traditional measurement methods. Various measurement principles can be used, e.g. capacitive measurements for the viable cell density and optical methods for the total cell density. The sensors provide reliable data for these parameters with very high resolution over the entire course of the process.
These sensors are useful in R&D, process development and also in production. However, there are a few important requirements that need to be met. The sensors should be easy to use, very robust and low-maintenance. They must be verifiable, and the generated data stream should be easy to integrate into existing systems. And, of course, the sensors should be usable under GMP conditions.
Whether and how the Arc sensors from Hamilton AG fulfill these requirements is the subject of this short presentation – you are cordially invited to attend.
Jochen Uhlenküken has been involved in the measurement of cell densities for many years.
As Head of Product Management at Innovatis AG, he was responsible for the development of the CEDEX HiRes® system. This automatic cell counter was revolutionary as it replaced the established manual methods. However, it also provided only a few off-line values during a process.
The emerging methods of in-line measurement with the Hamilton ARC sensors for viable and total cell density then seemed to make more sense to him. He has now been working as an application specialist at Hamilton AG for more than 10 years, supporting customer projects in Europe and Asia in the areas of R&D and production
Today, virus-based products like oncolytic viruses and gene therapies are part of the most promising biotherapies. The development of biomanufacturing processes for viral products is not a straight road. It is generally associated with process complexity and biological variability. In depth expression system characterization by adding biological data to standard chemical data will help to understand bioprocesses. With a close collaboration between Naobios and Gensensor, case study from Vero cell substrate-based process will illustrate how transcriptomic data may help to understand and monitor biological variability linked to bioprocesses.
Anne-Sophie has a PhD in cell biology and is engineer in biotechnology. After working on cell stress and death pathways, Anne-Sophie specialized in the development of advanced therapy medicinal product. Now Principal Scientist at GenSensor, she is in charge of identifying biomarker panels on different expression systems and leads, with her team, the company’s internal research projects and scientific collaborations.
Comprehensive Quality by Design (QbD) and PAT solutions enable manufacturers to monitor critical quality attributes and provide closed-loop control in real time.
PAT supports automated, multi-instrument, holistic quality assurance; provides timely critical quality predictions; and captures all necessary, regulatory-compliant data and metadata.
In « Future-Proofing with AI-Powered Bioprocess Development, » we dive into how AI transforms the bioprocess development cycle by offering unparalleled insights into complex parameter interactions. AnalysisMode’s innovative technology stands out by swiftly analyzing intricate data sets, revealing deep process insights, and simulating optimal next steps. This capability addresses the urgent need to understand detailed processes with limited time. AI’s predictive modeling enhances process development, understanding, and optimization, ensuring efficient and precise bioprocessing tailored to the intricate demands of the biopharma industry.
Belma Alispahic is the Chief Scientific Officer and Co-Founder of AnalysisMode. At AnalysisMode, she leads the development and implementation of SimCell, an AI-powered bioprocess modeling solution. Belma focuses on enhancing SimCell’s capabilities to optimize complex bioprocess parameters, integrating digital twins into biopharmaceutical workflows. She holds a Master’s in Applied Biotechnology from Uppsala University and a Bachelor’s in Genetics and Bioengineering from International Burch University. Her work bridges science and technology, driving innovation and efficiency in bioprocess development and optimization.
During bioprocess development, organizations typically utilize highly fragmented digital ecosystems — such as combinations of electronic lab notebooks (ELN), laboratory information management systems (LIMS), and data lakes — to capture and analyze information. This makes decision-making and PAT implementation very challenging. In this talk, we’ll focus on the design and optimization of bioprocessing workflows, including upstream processing (USP), downstream processing (DSP), formulation, and cell line development (CLD). We’ll examine how Genedata Bioprocess®, a comprehensive workflow management platform, supports all stages of this development. It aids in designing advanced bio-manufacturing processes, selecting high-yield cell lines, optimizing media development, and ensuring efficiency in process scale-up. Genedata Bioprocess® integrates with robotics for automation and high-throughput processes, and streamlines the development of new or optimized processes. We’ll also cover how it enforces data integrity and compliance, streamlining the development of originator drugs and biosimilars for efficient, cost-effective processes that ensure the quality, safety, and efficacy of the final product. We will discuss technical innovations that enable structured CMC data capture, efficient analysis, and transfer to regulatory agencies. We will also discuss special requirements of new biologic modalities such as antibodies, bi- and multispecifics, cell and gene therapies, and RNA.
With over a decade of experience in the biotechnology industry, Maxime Rantz has established a robust career marked by significant contributions to upstream process development and management. Currently serving as a Scientific Consultant at Genedata since 2021, he leverages extensive expertise to support scientific advancements. Previously, he was a USP PD Team Manager at Celonic Group in Basel, Switzerland, where he led upstream process development projects and managed a team of scientists. Before that, at FUJIFILM Diosynth Biotechnologies, Maxime Rantz held a Principal Research Scientist role, where he acted as the upstream project technical lead focusing on mAb production using CHO cell lines.
The pharmaceutical sector, including bioproduction, is being impacted by the advent of AI, just like many other industries. In a highly regulated environment, the use of AI requires rigorous structuring and documentation. Process modeling represents one of the key applications of this digital transformation. A review of the different types of models used at each stage of the process, such as mechanistic models, hybrid models, machine learning, Gaussian processes, or Kalman filters, will be presented. Additionally, for a biologist, it is crucial to consider the purpose of these models. Depending on specific needs, such as in silico development, troubleshooting, process validation, or feedback control, a classification of the different types of models will be provided. The implementation of these tools requires access to relevant, structured, and high-quality data. This necessitates strong collaboration between biologists, data engineers, and data scientists, each bringing specialized expertise to define the best structure and use of the data. Finally, once these tools are implemented, process productivity could be doubled, with a reduction in development time by half. However, this new approach will require a high level of expertise to master the complex environment.
Eric Calvosa is a biochemical engineer working in R&D at Sanofi Vaccines as a Global Bioprocess Expert. Eric has extensive experience in cell culture and viral processes. For 5 years, Eric was also responsible for DSP (Downstream Processing) in the field of vaccines. Since 2021, Eric has participated in and coordinated several European projects, such as Inno4Vac, and French projects like Calipso, focusing on process modeling and databases development in bioproduction.
Biologics and especially the rapidly evolving field of Cell & Gene Therapy offers new therapeutic options for patients. However, as the development of these promising new therapies expand, there is a significant need for improved production methods and techniques that are reproducible and adhere to Good Manufacturing Practices (GMP) standards. This step is critical to ensure both the efficacy and safety of these therapies in human trials. Particularly, among the principal challenges is the complexity and scalability of the manufacturing processes required for a wide array of products. Each of these processes requires comprehensive evaluations for efficacy and rigorous analytical quality control. Multiple variables can influence the quality and performance of these products.
In response to these challenges, ACROBiosystems has developed a full range of solutions for Biomanufacturing including Critical Reagents and Raw Materials to support Early development, Process development, Quality Control to Large-Scale Manufacturing & Commercialization. In this talk you will also learn about solutions to develop a scalable stem cell expansion and differentiation process for cell therapy CMC and discover how multiplexing can accelerate quality control during manufacturing. Additionally, the speaker will delve into the importance of GMP-grade reagents and their significance in clinical phases and beyond.
At ACROBiosystems, Dr. Mourad FERHAT is the Regional Head of France and Benelux Region supporting Company’s strategy of raising awareness and promoting advanced GMP grade solutions for clinical manufacturing of cell and gene therapies within the EMEA division. With a PhD in Molecular and Cell Biology and over a decade of experience in the Lifesciences industry, Mourad brings a solid experience in Drug Discovery and Biologics development, Control and Manufacturing.
According to the recently published Biopharma Sustainability Review, 62% of the 800 biopharma leaders interviewed stated that Sustainability is a top priority for the next 5 years, however only 17% are confident in their ability to accurately measure Scope 3 carbon emissions.
How do we change this paradigm?
By driving collaboration across the value chain, which starts by the raw material we source until the end of life of the product we sell.
Cytiva is focused and invested in delivering for customers to accelerate decarbonization and achieving eco-design. We do that by heavy focus supplier excellence and data, data, data.
Thibault started his career at GE Healthcare where he held several Global Supply Chain positions, from Logistic Sourcing to Distribution strategy in France and in Germany.
In 2020, Thibault moved to Cytiva (Danaher Corporation) as part of GE Life Sciences sell off to Danaher where he took the Global Supply Chain Sustainability role. Thibault brings his passion for Sustainability and systemic changes and now leads the Sustainability transformation Strategy effort across Cytiva.
Discover how Saint-Gobain Bioprocess Solutions is helping to advance sustainability in biopharma through innovative solutions that address decarbonization and circularity.
As a key player in the biopharma value chain, we conduct comprehensive Life Cycle Assessments (LCAs) on our product portfolio to provide greater transparency for our customers.
Join this session to learn how we foster scope 3 quantification and explore our ongoing collaborations aimed at improving packaging and waste management.
Caroline is Sustainable Market Manager for Saint-Gobain Bioprocess Solutions since 2 years and has been working with the Group for the last 7 years. Caroline works to help Saint-Gobain and its businesses capture the full potential of sustainability as a major growth and differentiation driver, both at global and local levels. She has an expertise in sustainability since 10 years with an experience on sustainable construction, responsible purchasing and societal issues. She is graduated from Water and Environment engineering at ENSIL and then got specialised thanks to an advanced master on Environmental International Management at Mines ParisTech.
Clément will present how Virtual Twins can enhance sustainability in manufacturing for innovative therapies, by demonstrating how these technologies, coupled with AI can optimize production processes and drive innovation in pharmaceutical manufacturing facilities. Additionally, he will talk about digital sustainability initiatives, such as lifecycle assessment in the context of PLM, to help companies reduce their global environmental footprint in manufacturing and within their supply chains through advanced Supply Planning.
Clément Glace is a solutions consultant at Dassault Systèmes, where he is part of the Life Sciences organization. Clément has worked with several pharmaceutical companies to develop and support their business strategies in the field of virtual twins for manufacturing innovative therapies, thereby fostering efficiency and innovation in the industry. He is also dedicated to promoting sustainability in drug manufacturing, actively working on initiatives such as lifecycle assessment for bioproduction processes to help companies reduce their environmental footprint and improve sustainable manufacturing practices.
Even if China follows most of the Quality ICH guidelines, there are still specific CMC regulatory requirements that should be anticipated to fill FIH in China compared to US and EU requirements.
In comparison, Taiwan and South Korea will mainly follow the US and EU CMC requirements.
Carole is Regulatory Affairs Leader and CMC Pre-MA expert at Laboratoires Pierre Fabre. She graduated in 2006 with Master of Science degree (MSc) in Quality Control of medicinal products at the Faculty of Pharmacy – Paris XI University. She has over 17 years experience in CMC regulatory Affairs in small and biological molecules supporting CMC strategy from Phase I to Marketing Autorisation Applications. She is also involved in Rare Disease development (medicinal products with Prime and Breakthrough Therapy designations) and in the interactions with the Health Authorities for the optimization of CMC development plans.
Dr. Yucai Li Joined WuXi Biologics in January 2022 and is currently Executive Director leading EU CMC Management team. Sha has managed multiple early and late phase CMC programs with track records of successful regulatory filing. Dr. Yucai Li received her Ph.D. in Biotechnology from Lund University (Sweden) in 2001 and has been working in the biopharmaceutical industry for the past twenty-three years, including Lundbeck, AGC Biologics, Pfizer Healthcare and Swedish Orphan Biovitrum. Her expertise includes mammalian and microbial process development, process characterization & validation, as well as tech transfer & cGMP manufacturing supporting.
Process analytical technology (PAT) aims at real-time, sampling-free monitoring of bioprocesses, for instance at the upstream stage (USP), when suspensions of CHO (chinese hamster ovary) cells grow in bioreactors and produce monoclonal antibodies (mAbs). The advantages of in-line PAT over the off-line approaches are numerous, from scientific, economic and ecological points of view. Using light as a non-invasive PAT tool is one of the promising ideas that give rise to various technological solutions. Nevertheless, the implementation of novel PAT approaches is limited and still requires further progress in analytical instrumentation and its integration in the whole process.
In this talk, we plan to present a short overview of advances in implementation of molecular optical spectroscopy as a PAT tool in upstream processing of therapeutic antibodies we obtained in the framework of our interdisciplinary research project CLIMB’IN. The project uses analytical spectroscopy based on light absorption and/or multi-angle scattering, both elastic (Rayleigh) and inelastic (Raman) for quantitative monitoring of multiple critical process parameters (CPPs). The advances reached by the CLIMB’IN consortium involve instrumental design and experimental protocols, with a particular focus made on machine learning algorithms. Brought together, these advances allow to improve the relevance and the robustness of the corresponding PAT approaches required for their industrial implementation.
In the realm of biopharmaceutical production, Chinese Hamster Ovary (CHO) cells have emerged as the main expression system for recombinant therapeutic proteins (RTPs), despite the availability of several alternative cell lines. CHO cells are among the most widely used worldwide for their unique advantages, e.g, the variety of post-translational modifications that closely mimic those found on human cells (Stach et al. 2019); their high degree of biosafety due to their low risk of propagation of human viruses infection (Lalonde and Durocher, 2017); their adaptability from adherent to suspension cell culture in serum-free media (Davami et al. 2014). Thanks to these combined attributes that solidified the position of CHO cells, they have become the gold-standard of the bioindustry and are responsible for the production of approximately 70% of all marketed RTPs (Pereira et al., 2018; Stolfa et al., 2018; Dziomba et al. 2023).
Fetal bovine serum (FBS) is commonly used as a supplement to basal media for in vitro cell cultures (including mammalian, animal, insect, and bacterial cells). Many studies have revealed its rich composition, containing essential macro- and micronutrients such as growth factors, adherent factors, amino acids, hormones, and vitamins (Michael Butler et al. 2020), which are crucial for proper cell function. In addition to the ethical issue, increasing demand, high cost, significant contamination risks (bacterial and viral), and batch-to-batch variability of FBS prompt us to seek alternatives. To reduce or eliminate FBS use, we have decided to implement culture media with various plant protein hydrolysates. Although serum-free media have been available for several decades, and their widespread adoption has increased, despite the fact that their compositions are undefined for users. Our goal is to make these serum-free media more accessible considering that serum-free media cost about 1.5 to 3 times more than serum-containing media.
Several publications highlighted the effects of vegetable proteins hydrolysate (peptones) as supplements in basal media, i.e : the enhancing of the cell growth and productivity of recombinant proteins (Burteau et al. 2003; Michael J. Betenbaugh et al. 2020). Some publications have shown an enhancing of the volumetric productivity more than 100%, and a 40% increase in cell number (Davami et al. 2014; Davami et al. 2015). Then, the composition of these plant hydrolysates varies according to the plant source and the production process. Thanks to their vegetable origins there are neither ethical issues, nor health standards.
In the present study, the effect of different peptone concentrations on the CHO-K1 cell line under various culture conditions (adherent/suspension) in a basal medium with a 10-fold reduction of FBS have been evaluated. Supplementation with wheat peptones at defined concentrations increased the viable cell density of CHO-K1 in adherent conditions by 190 – 265%.
Additionally, the suspension culture exhibited different results compared to the adherent conditions. In suspension cell culture, only three peptones – wheat, soy, and pea – enhanced viable cell density compared to the medium without hydrolysates. Actually, the only peptone supplementation is not enough to be completely serum-free, but that can reduce the FBS consumption.
Fabien Compeau is a researcher at both Organotechnie and Université Sorbonne Paris Nord, within the Tissue Engineering Research Unit. With a solid foundation in molecular and cellular biology. His current work centers on developing serum-free media. He completed three years of study at CY Cergy Paris Université and two years at Université Paris Cité. His internships provided valuable experience at the Institut de Recherche Criminelle de la Gendarmerie Nationale, the Institut Jacques Monod, and the Institut Pasteur, his research
focused on cell signaling, dynamics, and differentiation.
The Solution Molecular Microscope is an innovative technology that enables the observation of protein molecules in solution in true form. This technology doesn’t require any particular limitations (crystallization, freezing, fixation, labeling, and so on…) as other structural analysis methods. It is a valuable technology for scientists in protein structural analysis and for every biopharmaceutical scientist who wants to see the actual shape of protein molecules in solution.
We asked some scientists to try using our new technology. It showed a different structure to that obtained using existing methods and captured a 3D structural image that supported the actual movement of the protein. We could have excellent results because no one has ever seen the actual molecular structure in a living state. Biopharmaceutical developers, who previously relied on guesswork to culture biopharmaceuticals, are now witnessing a paradigm shift. The Solution Molecular Microscope is turning their understanding of molecular structures upside down, providing them with a new, exciting perspective.
I joined Rigaku Corporation in April 2003, after getting a Master’s of Shimane University, Interdisciplinary Faculty of Science and Engineering. I was a software engineer of the X-ray Instrument division until May 2015. I started my new role in the same division as a head of the molecular structure analysis business.
The French National Research Program on Biotherapies and Bioproduction of Innovative Therapies (PEPR-BBTI) is one of the major initiatives within the France 2030 acceleration strategy on innovative therapies. With a budget of 80 M€, this program aims to consolidate the France’s leadership and competitiveness in the field of biotherapies and their associated manufacturing. It focuses on 4 axes: (i) accelerating the deployment of gene therapies, (ii) anticipating the rise to industrial scale of cell therapies and the emergence of tissue therapies, (iii) developing bio-manufacturing processes, and (iv) supporting emerging biotherapies. It specifically support the French academic research and promote their connections with industrial and hospital players.
Our goal is the keep you informed about the ongoing and upcoming actions supporting the community. Current actions include funding of 12 priority projects, and launching a first call for proposals. Additionally, we will soon launch a call for expressions of interest to foster cross-disciplinary collaborations between our community and data scientist, chemists and experts in ethics and social sciences, with the aim of jointly developing novel disruptive biotherapies and anticipating their manufacturing. We also offer financial supports to young scientists for participating to trainings, international exchanges and/or conferences and for consortia responding to European calls. Are you interested in learning more? Join us for our lecture!
Dr. Fanny CAPUTO, PhD. Material scientist by training she works at CEA-DMTS as project manager of the French Research Program Biotherapies and Bioproduction of Innovative Therapies (PEPR-BBTI) and of the European RESILIENCE framework partnership. Before, she worked at CEA-LETI (2015-2019), SINTEF Industry (Norway, 2019-2021) and at the French Metrology Institute (2021-2023), where she has acquired 10 years of experience in the management and coordination of European projects in the field of Health-Tech. Futhermore, she is an expert in the physical-chemical characterisation and pre-clinical development of nanomedicines, in regulatory science and in standardisation. She is a nominated expert at the NANO Working Party (Nanomedicines) of the European Pharmacopoeia (Ph. Eur.).