Wednesday, September 25, 2024 - Day Two of Main ConferenceWednesday, 25 September 2024 - ET (Eastern Time, GMT-05:00)

Cell therapies are driving clinically meaningful benefit in some haematological malignancies. Extending this success to solid tumors has proved challenging, in part due to the complex and hostile tumor microenvironment (TME) that limits the activity of cell therapies.

This presentation will provide insight into AstraZeneca’s approach to overcome these challenges, including our novel preclinical framework and innovative strategies to ‘armor’ cell therapies to resist immune-suppression in the TME. By advancing a broad portfolio of CAR-Ts and TCR-Ts, we are unlocking a breadth of intra- and extra-cellular targets in cancer treatment, and I will share preclinical and clinical data demonstrating their early promise in hard-to-treat solid cancers. Data will also be presented showing the exciting potential of a dual-targeting CAR-T in haematology.

Looking to the future, there are still many challenges that prevent the widespread adoption of cell therapy and I will share AstraZeneca’s vision for overcoming this, with the goal of bringing cell therapy to more patients globally.

Gather around the 'fire' for a captivating conversation with our Keynote Speaker: Mark Cobbold. Gain candid insights, get inspired, and dive deeper in a relaxed, conversational setting hosted by BioProcess International/Insider Editors & Thought Leaders.

Cell and Gene Therapies have brought great advances to the treatment of severe diseases previously deemed untreatable. Despite commercial and clinical success of AAV-based Gene Therapies (7 approved in EU and US) and the ever-increasing number of on-going clinical trials in this field, significant manufacturing challenges still need to be overcome to enable easier and global access of these life changing therapies.

The main challenges for the manufacturing of such therapeutics are: production costs per dose as these manufacturing processes still lack robustness and suffer from batch failures. This can largely be explained by the fact that these novel therapeutics - at the interface of medicine and biotechnology - do not yet benefit from highly standardized, optimized, modular and flexible platform processes, as it is today state-of-the-art for the manufacturing of e.g. monoclonal antibodies.

The presentation will focus on how the ELEVECTA platform and more precisely the stable ELEVECTA cell line, is one of the emerging solutions towards the current challenges in the field of AAV manufacturing.

As more and more therapies require temperatures down to and below -80 degrees Celsius, the need for primary containers that can maintain integrity throughout the cold chain has become more critical than ever. Testing and data will be presented that demonstrates that primary containers have a range of failure modes even when protective secondary packaging is utilized. Understanding these failure modes and ensuring primary packaging is validated for cold chain application (such as Frozen Impact Durability, Freeze/Thaw cycle, Long-Term Frozen Storage and shipping and distribution testing) allows end users to minimize the potential for integrity problems during high volume production.

• How to improve operations to make more reliable, faster, and easier sterile connections.
• A complete and validated method for sterile fluid transfer without Bios Safety Cabinets or capital equipment expenditures.
• How aseptic connector solutions support scale-up and scale-out while addressing processing concerns.

Emerging novel therapeutic modalities present challenges in the context of their analytical evaluation within a GMP environment. Platforms enabling reproducible, robust methods can ensure efficacy, safety, and regulatory compliance. Innovative, scalable workflows boost efficiency and productivity, while reducing costs, from discovery through preclinical development.

Microbial QC testing is an essential part of the pharmaceutical manufacturing process, and the accuracy of these assays is dependent on high-quality reference materials. Learn how ATCC is using next-generation cryobiology to alleviate many of the challenges associated with the use of reference materials to help reduce handling time.

Head down to the Poster Wall in the Exhibit Hall for some fresh coffee, cookies, exciting new research and a chance to speak with the poster authors!

Kindly sponsored by ATCC

• The turnaround in the funding environment and how that is affecting the supply sector
• Major M&A over the past few months in the outsourced and supplier space
• The widening modality focus of the industry and how vendors and CDMOs are responding
• Macroeconomic factors (BIOSECURE and China, specifically)

• How PAT provides deeper insights into the bioprocessing stages, leading to improved control and optimization
• Ensuring product quality and consistency through real-time monitoring and control
• Importance of robust data management and integration systems
• Real-world examples of PAT implementation in upstream bioprocessing, highlighting the benefits and challenges faced
• Addressing the cost implications of implementing PAT and demonstrating ROI

We present a digital twin model-based process control (MPC) strategy for the successful glucose feeding in a bioreactor using only daily offline measurements. Our MPC strategy is composed of two kinds of formulars for predicting 1) glucose feeding amounts at daily sample time-points and 2) glucose feeding amounts at unsampled time-points.

Perfusion bioreactors outperform fed-batch cultures in volumetric productivity due to prolonged cultures and continuous harvesting. Higher perfusion rates increase volumetric productivity, while often minimally changing the product titers. Amino acid depletion, especially of tyrosine and cysteine, often limits product titers in both perfusion and fed-batch bioreactors. The Ambr250 HT Perfusion system (Sartorius) was used to quantify the effects of varying amino acid and glucose concentrations independently. Cell bleeds were varied to reach several stable steady states. Amino acid concentrations were monitored using REBEL (908 Devices) at-line spent media analyzer to quantify amino acid consumption rates across the cell-specific feed, perfusion, and bleed rates. The effect of varying glucose and amino acid concentrations independently will be presented.

Key take-aways:

Understanding perfusion bioproduction enables data-driven optimization for higher productivity

Amino acids have been identified as key limiting factors in perfusion and batch processes

Varying glucose and amino acid feedings could reach stable target viable cell densities by controlling the perfusion and bleed rates.

The presentation provides an overview of the benefits and the challenges associated with the intensification of bio-manufacturing processes. The author will present different technologies such as Multi Column Chromatography and Rapid Cycling Chromatography and a software intensifier tool available to improve downstream productivity while maintaining the quality and safety of biologics. Bas du formulaire Real life case studies will show how these technologies can be implemented in clinical and commercial processes and quantify the cost saving, footprint reduction, speed, productivity, flexibility and sustainability benefit they can bring to our industry.

Control and management of materials is a key pillar of GMP manufacturing. An initiative is in progress which aims to harmonize the approaches of material management between clinical and commercial Drug Substance production sites to increase efficiency and supply chain sustainability within the organization. We will present the background and drivers, strategies, and current status of this initiative.

With the exciting advancement of new technologies such as RNA-based vaccines and therapeutics also comes challenges. Bottlenecks in analytical method development, particularly for multivalent vaccines and drugs, may limit the speed and agility with which new vaccines and therapeutics can be developed and released. This presentation will provide a technology overview and highlight applications of the VaxArray Platform, a multiplexed, microarray-based analytics platform engineered to address a variety of vaccine and therapeutic-relevant applications in protein quantification, mRNA construct quantification and characterization, and serum antibody quantification in a single instrument platform. The VaxArray Platform is comprised of a small-footprint benchtop fluorescence imaging instrument, associated GMP-compatible software, and a variety of off-the-shelf high throughput reagent kits. With multiplexed measurements, VaxArray delivers a range of analytical results and assesses multiple analytes simultaneously with rapid times to result of less than 2 hours and very simple workflow and execution. We will highlight VaxArray applications that include measurements of mRNA construct identity and quantity in multivalent vaccines, quantification of intact and capped mRNA, measurement of multivalent vaccine antigens in traditional vaccines as well as in vitro expressed antigens post-transfection of mRNA constructs, and serum antibody quantification. For projects that fall outside of applications supported by off-the-shelf kits, we will discuss how the Expert Services team at InDevR can rapidly provide validated custom microarrays functionalized with a variety of different biomolecules.

• A chemical cross-linking mass spectrometry workflow has been developed for investigating interactions between host cell proteins (HCPs) and monoclonal antibodies (mAbs).
• The interaction sites between mAbs and several HCPs have been identified with high confidence using the cross-linking mass spectrometry method.
• This study highlights the effectiveness of chemical cross-linking mass spectrometry for studying proteinprotein interactions during antibody drug development.

Recombinant proteins represent almost half of the top-selling therapeutics—with over a hundred billion dollars in global sales—and their efficacy and safety strongly depend on glycosylation. In this study, we showcase a simple method to simultaneously analyze N-glycan micro- and macroheterogeneity of an immunoglobulin G (IgG) by quantifying glycan occupancy and distribution. Our approach is linear over a wide range of glycan and glycoprotein concentrations down to 25 ng/mL. Additionally, we present two case studies using this tool for quantitative analysis. First, we demonstrate the effect of small molecule metabolic regulators on glycan heterogeneity using this approach. In particular, sodium oxamate (SOD) decreased Chinese hamster ovary (CHO) glucose metabolism and significantly reduced IgG glycosylation through upregulating reactive oxygen species (ROS) and reducing the UDP-GlcNAc pool. Then, we use a modeling approach combined with design-of-experiment (DoE) to validate glycan macroheterogeneity variation likely originated from metabolism alterations as a versatile control metric. Overall, we suggest glycan macroheterogeneity as an attribute should be included in bioprocess screening to identify process parameters that optimize culture performance without compromising antibody quality.

• Attracting, recruiting and retaining experienced staff remains a key priority for companies.
• Recruitment strategies: Actively seeking out talent from diverse backgrounds and ensuring that recruitment practices are free from bias.
• Mentorship programs: Pairing young professionals with seasoned executives to ensure the next generation of leadership is as diverse as the populations they serve.
• Early talent and how to invest and engage early to ensure we don’t leave people out of this potential pipeline.
• Consortiums and Associations - Investing in early career programmes to create employment pathways.
• Finding talent to fuel innovation - Increasingly seeking talent with AI and data skills in order to remain competitive as digital technology drives innovations
• How can pharma companies support early career scientists through non-traditional pathways into the industry?
• The impact of digitalisation: What skills will give new hires an edge?
• Industry growth and its implications for career development

Continuous manufacturing has become more prevalent across the biopharmaceutical industry in recent years. The ambr250ht perfusion system stands as a promising option for bench-scale culture work, but first must be proven as a replacement for the more common 3L scale. Through statistical analysis, the differences and similarities between these scales can be investigated to qualify their equivalence

Generic Raman spectroscopy models, built using data from multiple processes, offer a method for streamlining Raman model development and integration in upstream bioprocessing. Effective implementation of generic Raman models requires consideration of several factors, such as the presence of any biases in the calibration dataset. The large volume of data used to develop generic Raman models also makes them ideal for creating hierarchical Raman models, which use the outputs of one or more base models as the inputs for a new model—e.g., cell culture pH.

Antibody production relies on a broad range of raw materials. Most of these raw materials are used in various industrial applications and their specifications have not been developed with antibody production in mind. Chemical or physical characteristics, contaminants and impurities may diverge between lots and can lead to variability in performance of these raw materials in antibody production, even though these raw materials work well in other applications. This leads to process inconsistencies, yield loss, and can even affect the characteristics and quality of the final drug product. The Biopharma industry has recognized the importance of raw material consistency and efforts have been made to better understand the requirements for raw materials in bioprocessing. Raw material suppliers are using the learnings of the Biopharma industry and started developing application-specific products for the biopharma industry, which reduce the risk of performance variations. One example is BASF’s Kolliphor® P188 Bio, which was developed to address performance variability in cell culture. We would like to share our learnings from developing raw materials with Biopharma in mind and give an outlook on how raw material suppliers can support the Biopharma industry to achieve more robust and efficient processes.

The current biologics market has seen a shift toward the proliferation of New Molecular Format (NMF) molecules such as Bi/Tri-specifics and increasingly exotic fusion proteins. As the diversity of these therapeutic pipelines rapidly expands to encompass these novel formats, unique and exciting challenges have emerged in downstream development (DSD) since most of these product types lack well-defined, templated downstream platforms. The diversity in the structures and physiochemical properties of these molecules continues to drive innovation within process development that necessitates the use of a toolbox approach relying heavily on data-driven decision making. Here, the background of Lonza’s experience and offerings for different NMFs will be summarized, followed by two detailed NMF case-studies highlighting a DSD approach tailored to the specific demands of the product and project, where unique non-platform approaches were utilized to solve interesting development challenges.

• The diversity of monoclonal antibody therapeutics has expanded significantly in recent years resulting in new challenges for downstream processing. Here, we present 2 studies to highlight our toolbox approach to significantly reduce impurities such as host cell proteins, aggregates, and endotoxin, and achieve viral clearance from widely used expression systems.
• Study 1: We demonstrate significant reduction of impurities, while achieving high target protein recovery by using a novel mixed mode chromatography resin, HCPure™, designed to operate in a unique chemical space.
• Study 2: We examine the potential of 2 orthogonal adsorbents, HCPure™ and Q PuraBead® to remove noninfectious viral surrogates for Minute Virus of Mice and retrovirus (Cygnus Technologies).

The last twenty years of bioprocessing has seen significant advancement in robustness and speed to manufacturing in no small part due to templatization of processes and leveraging CHO cell lines and monoclonal antibody therapies. Traditional (non-mRNA) vaccine manufacturers target accelerated timelines as well, but rarely have a standard template of processing tools to rely on. This talk will discuss strategies developed for drug substance and drug product development which optimize development time, scalability and tech transfer success.

• The importance and advantages of microbial systems in biopharmaceuticals
• Platform for non-mAb biopharmaceutical development
• High Throughput process development
• CASPON technology a solution for the development of therapeutic peptides
• Future prospects, such as sustainability and competitiveness

Over the last decade, biopharma industry has seen major transformation in terms of success found in manufacturing modalities beyond MAbs viz. VV, pDNA or mRNA along with increased efficiency on MAb production process! This has resulted in 2000L as preferred manufacturing platform to generate required clinical test materials. Cytiva’s FlexFactoryTM offering has established itself as preferred manufacturing solution at 2000L scale evident from 150+ installation across the world. FlexFactory provides advantage in terms of Cytiva’s platform products available to support inoculum through Bulk drug substance and drug product filling manufacturing solution. This platform-based products with productized automation and qualification services are delivered through highly professional project management offering available at fixed cost & meeting customer schedule requirements. We will review fact-based advantages of FlexFactory - Cytiva’s platform-based capacity expansion solution.

Traditional chemistry, manufacturing, and control (CMC) development lifecycles of monoclonal antibodies are rapidly evolving to enable acceleration and unmet patient needs. The necessity of an informed and meaningful control strategy to ensure product quality in an accelerated program is closely tied to the advancement of product development through commercialization. The BioPhorum Development Group presents a consensus-driven review of potentially impactful and non-impactful process parameters that may inform process characterization studies for upstream, downstream and drug product unit operations. Guidance on the application of analytics through in-processing testing and product specification is incorporated for the support of process understanding. This document represents recommendations for a foundational understanding of process parameters which sets the stage for product-specific studies. Cross-company review of process parameters with potential impact to critical quality attributes or process performance indicators is a springboard to advance accelerated CMC development. These guidelines will aid in robust process understanding whilst keeping pace with the rapidly changing clinical needs of modern healthcare.

Digital PCR is vital in cell and gene therapy development due to its precise, curve-free absolute quantification. Automating the dPCR workflow with a modular, scalable solution can help improve efficiency, reduce variability, and enhance productivity. The QuantStudio Absolute Q AutoRun dPCR Suite integrates advanced technology with intelligent lab automation, enabling hands-free dPCR for efficient processing. This presentation explores how these innovations facilitate accurate and precise absolute molecular quantification for analytical evaluation workflows.

The volumes of data generated by upstream bioprocesses during development, technology transfer and GMP production are only as good as the tools to make the data available for consumption and advanced data analytics. This talk will provide current highlights from our 12-year journey digitizing bench and pilot scale bioreactor processes to enable paperless data aggregation and generation of persona dashboards for daily analysis by data consumers and executives alike.

• A novel, caprylate-based mixed-mode resin (POROS Caprylate, Thermo Fisher Scientific) was evaluated with a panel of mAbs and mAb derivatives for high-capacity HMW removal.
• Each molecule’s operational space was screened in filter plates and minicolumns for aggregate removal as a function of loading.
• Optimized conditions were evaluated at varying conductivity levels.

The biopharmaceutical industry is increasingly confronted with the dual challenges of complex product demands and a volatile market landscape, necessitating unprecedented levels of supply chain agility and resilience. This presentation addresses the critical role of digital innovation in transforming biopharma supply chains, enabling them to adapt swiftly to market fluctuations and unexpected disruptions. We explore the integration of advanced technologies such as artificial intelligence (AI), and machine learning (ML) to enhance visibility, optimize operations, and improve decision-making processes. Through case studies and industry insights, we demonstrate how digital tools can facilitate precise inventory management, robust cold chain logistics, and regulatory compliance, thereby reducing waste and ensuring timely delivery of vital products.

BioPhorum's Digital Plant Maturity Model (DPMM) is a framework designed to guide and benchmark the digital transformation of manufacturing facilities, particularly in the biopharmaceutical industry. It outlines five levels of digital maturity, ranging from pre-digital plants to fully automated and adaptive plants with end-to-end value chain integration. The model has evolved to reflect advancements in technology and industry practices, making what was once considered 'visionary,' such as the use of AI, now increasingly commonplace.

The DPMM serves as a common language that facilitates external discussions with vendors, who can align their technology solutions with the model's levels. This alignment helps businesses develop their digital maturity strategies more effectively. The model also supports benchmarking across different sites and networks, recognizing that each may have varying levels of digital maturity. This understanding allows for strategic investment decisions to enhance digital capabilities where they are most needed, without uniformly applying the same level of maturity across all sites or networks.

The assessment tool is versatile and can be applied to businesses of all sizes, from small sites with fewer than 100 people to large sites with over 5,000. It enables quick, high-level assessments that provide immediate insights and benefits, helping businesses understand their current position and plan their digital transformation journey accordingly. Whether it's identifying areas for investment or building a roadmap to achieve desired maturity levels, the DPMM 3.0 is a valuable tool for driving digital progress in manufacturing.

The DPMM is the result of a collaboration by BioPhorum member companies and is based on tried-and-tested examples and the collective knowledge of industry leaders.