RXX - Session Topics

Oral session 1:   The Adventure Begins at Harvest

Arick Brown, Amgen
Brandon Christensen, Visterra

Recovery of Biological Products has never had a session dedicated to harvest innovation until now! Join us and submit an abstract on this worthy subject that has too long been overshadowed during this conference’s storied history. The adventure at RXX literally begins at harvest, and we encourage the intrepid to join us in this inaugural program as we navigate the diverse and ever-growing bioreactor harvest related challenges faced by today’s process developers and manufacturers.

For this session we are seeking contributions on familiar topics with a new twist, like cell culture clarification adapted for extreme titers and cell densities, perfusion culture separation innovations that simplify processes and eliminate fouling, and tangential or normal flow filtration with innovations in media that enhance performance and product quality. We also want to explore the growing field of viral vector bioprocessing and innovations in upstream separations of AAVs, lentivirus, oncolytic and retrovirus, as well as macrophages, cell therapies and CAR-T therapeutics.

We want to hear about enhancements in separations via new, single-use systems, as well as continuous operating strategies and the benefits that new technologies are bringing to these areas in terms of processing scale and facility and drug manufacturing costs. We want to hear about case studies in development and scale-up and how challenges in the lab were solved by innovation, be it through novel end-user science or through vendor-led initiatives that have given you the tools to overcome your most challenging obstacles.

The Adventure Begins at Harvest session is meant to be the confluence of a broad range of topics, and like streams flowing into a river, the convergence can create waves, but herein lies the thrill of the ride. Grab a paddle, join us on our adventure, and submit an abstract to help make this first-ever dedicated session on harvest the exciting ride it’s destined to be.

Oral session 2:   Advances in Structure-Function Understanding and Developability Assessment for Novel Biologics

Chen Wang, AbbVie
Peter Tessier, University of Michigan

Diverse and complex biologics, vaccines, cells, and vectors for gene therapy comprise a significant and growing category of products for the treatment of human diseases. Early developability assessment of these therapeutic candidates as well as understanding their structure-function relationships are critical aspects in selecting modalities that can be manufactured with a robust and cost-effective process, while at the same time meeting the expected quality target product profile.

Key elements of developability assessment include expression level, ease of manufacture, facility fit, and stability during production, formulation, and storage. Evaluation of physical and chemical properties of biologics candidates, such as viscosity, solubility, aggregation propensity, stability, post-translation modification hot spots (oxidation, deamidation) and non-specific binding, is important to the design and optimization of the molecule, manufacturing process and formulation given the potential impact on yield, cost, target product profile, drug delivery and safety.

This session will highlight the latest advancement in structure-function characterization and developability strategies applied across a range of biotherapeutic modalities, including mAbs, Fabs, multi-specifics, ADCs, AAVs, and ASO. We invite presentations and case studies that demonstrate the applications of state-of-the-art computational and experimental methods and tools to evaluate, predict and improve the developability of complex biotherapeutic modalities, as well as discuss and address key challenges encountered in the CMC aspects of these novel therapies.

Topics of interest include (but are not limited to):

  • How can traditional workflows be accelerated? Novel approaches and technologies applied to developability assessment, risk mitigation and structure-function analysis, especially for hard-to-predict biologics.
  • What can be done in silico? Computational algorithms to predict physical and chemical liabilities (e.g., instabilities) of biologics, as well as the relationships between such properties and processing parameters, yield and productivity. Structural modeling to predict surface properties of biologics and their connections to solution and purification properties.
  • How can new experimental methods be used to improve developability? Novel experimental methodologies used in candidate formulation assessment, pre-formulation screening, stability and other developability properties. Use of experimental measurements for predicting accelerated and long-term stability properties.

Oral session 3:   Mission Impurity Characterization: Advances, Challenges, and Regulatory Insights across Modalities

Kristin Valente, Merck and Co., Inc.
Andre Dumetz, GSK

For all modalities (e.g., protein biopharmaceuticals, vaccines, and cell and gene therapies) understanding the impurity profile is essential to ensure product safety, potency, and efficacy. Impurity characterization is advancing at high speed in parallel to the rapidly evolving industry landscape. Advances in equipment sensitivity, the development of new analytical techniques, and the evolution of fundamental product understanding have enabled novel methodologies for improved impurity detection; also, the explosion of molecule diversity has facilitated new insights through the adaptation of traditional techniques to novel modalities.

This session will feature case studies and innovative applications of impurity characterization and clearance across both traditional biopharmaceuticals and new modalities. Of particular interest are abstracts that highlight:

  1. discovery of new or challenging impurities and their consequences for process development, scale up, and file registration
  2. pioneering traditional assays to new modalities
  3. the quest for novel techniques for historical and new purification challenges
  4. exploration of impurity commonalities and differences across modalities
  5. the development of novel Quality by Design and regulatory approaches to tackle exogenous and/or product-related impurities

This session will help to forge a path towards the future of impurity characterization as a cornerstone of all biopharmaceutical modalities, making a lasting impact on industry progress and patient well-being.

Oral session 4:   Escapades of a Continuous Nature

Andrew Tustian, Regeneron Pharmaceuticals
Daniel Bracewell, University College London

The field of biological medicines is witnessing a Cambrian explosion in new modalities, moving beyond traditional antibodies. These new modalities include viral vectors like lentivirus and AAV, various RNA forms, CAR-T and cell therapies, plasmids, and more. Our task, as process development scientists, is to transform these innovations into reality by developing robust, cost-effective processes that consistently deliver safe and effective products for not just the next clinical trial but for years to come.

Adapting to these new therapies goes beyond just modifying existing practices. Some products are individual/autologous therapies, while others target small patient populations. There are also personalized vaccines tailored to a patient's disease state. Additionally, the impact of the pandemic and vaccine nationalism has affected government policies. All of this raises crucial questions about the future of manufacturing infrastructure and supply chains. Proposed solutions include manufacturing at the bedside, adopting modular facilities, and re-evaluating host organisms that have proven valuable in the industry. Sustainability is also a significant focus, aiming to reduce raw material and energy consumption, while improving financial sustainability through reduced costs and time to market.

Session Objectives: This session aims to shed light on future technologies and strategies that address the aforementioned challenges, with a focus on reducing costs and time to market while ensuring commercial production and patient access to these new modalities. Topics of interest include:

  • Advances in continuous downstream processing for cost reduction and increased sustainability.
  • Insights into newer biological modalities and their purification technologies for the future.
  • Addressing challenges related to personalized or new modality medicines with smaller lot sizes, especially in terms of purification and strategies for assuring lot quality with limited material.
  • Strategies for manufacturing and supply chain management, encompassing equipment and facility design.
  • Approaches to accelerate bioprocess development and reduce time to market.
  • Strategies for increasing patient access, particularly in low- and middle-income countries.

By exploring these key areas, we aim to foster innovation and collaboration in the field of bioprocessing and pave the way for a more promising future of biological medicines.

Oral session 5:   Principles, Strategies and Highlights of Modelling and Data Analytics in Biomanufacturing

Sophie Karkov, Novo Nordisk
Eric von Lieres, Research Center Jülich

Systematic acquisition, storage and interconnection of comprehensive data from bioprocess design, scale-up and operation provide unprecedented information for data analytics as well as for mechanistic and hybrid modeling. This opens manifold opportunities to better understand and more rationally configure, monitor and control downstream processes. Data science (machine learning/artificial intelligence) is currently developing extremely quickly with groundbreaking methods and tools emerging at breathtaking pace. At the same time, digital twins coupling detailed models of individual unit operations and linking them with the actual physical process and real-time data are becoming mature and available.

This session will highlight novel technologies, management strategies, and exemplary case studies on knowledge-based and data-driven decision making. How do we reduce and focus experimental work to maximize information gain, extract and visualize key indicators from complex data sets, predict system behavior by transferring knowledge across molecules, facilities and scales and evaluate process options from both a technological and economical perspective?

We particularly encourage contributions addressing one or more of the following questions:

  • How do we optimally use digital twins for designing, monitoring and controlling bioprocess operations?
  • Can explainable artificial intelligence enable us to comprehend and trust the results of machine learning algorithms?
  • How do we use hybrid and physics-informed modeling to integrate pervasive data with mechanistic knowledge?
  • How do we apply uncertainty quantification to rationally manage risk caused by variable feedstocks, imperfect equipment, incomplete causal understanding, etc.?
  • How do we internally store, share and protect data (data lakes) in a findable, accessible, interoperable and reusable (FAIR) manner? Note that FAIR does not necessarily imply open or free.
  • How do we benefit from and contribute to open software projects and research alliances/academic communities with enabling technologies and common practices in pre-competitive stages?
  • Where does it make sense to join forces in a collaborative way rather than competing?
  • Where can the industry profit from shared information and databases on standard molecules, materials, devices?
  • Which personal experiences, learnings, opinions can we share from everyday life, big successes and glorious failure?
  • Which strategies do companies have to utilize emerging technologies in modeling and data science in the future? What are we still waiting for?

Oral session 6:   Adsorptive Separations Across the Universe of Biologics

Stefano Menegatti, North Carolina State University
Kevin Brower, Sanofi

Adsorptive separations are leveraged to purify a variety of modalities, from protein constructs for therapy and vaccination to the emerging class of gene-editing products (GEPs). New designs for established and emerging therapeutics are constantly being introduced and the continuous evolution of design represents a challenge for biomanufacturing. Downstream processing faces feedstocks with increasing complexity in terms ofimpurities and biomolecular lability of the products. Addressing these challenges calls for creative innovation of adsorptive technologies, particularly focusing on the following key areas:

  1. Ligands for affinity-based capture and mixed-mode polishing. Submissions are encouraged that introduce ligands targeting products for which the current biorecognition toolbox is either limited or absent, including: advanced protein constructs such as bi- and multi-specific monoclonal antibodies and their engineered fragments, recombinant enzymes, blood factors, and fusion proteins; viral vectors for gene and cell therapy, vaccination, and oncolytic applications,; nucleases for cell and tissue engineering such as CRISPR-Cas, TALEN, and ZFNs; oligo-nucleotide for gene silencing or activation such as siRNA, miRNA, and antisense oligonucleotides (ASOs); and therapeutic cells for cancer therapy and regenerative medicine such as stem or progenitor cells, Car-T and Car-NK cells.
  2. Materials and designs of chromatographic substrates. Submissions are also invited that focus on the intro-duction or characterization of base materials with new composition, whether natural or synthetic, and design/fabrication technologies, such as core-shell beads, 3D-printed monoliths, and membranes. The impact of composition and design on purification performance and lifetime, fluid dynamics and mass transfer, as well as scalable manufacturing and recycling, are important aspects for inclusion.
  3. Purification modalities and process design. We also solicit the presentation of creative designs of adsorptive operations that promote flexibility across different product variants (e.g., virus serotypes or classes of nucleases) and robustness to diverse feedstocks produced by different cell lines (e.g., mammalian, fungal, bacterial, and vegetal). Novel adsorptive technologies conducive to rapid or continuous manufacturing beyond established approaches such as sequential multicolumn or simulated moving bed chromatography may also be submitted.

We also strongly encourage the speakers to complement the scientific and engineering aspects of their innovations with qualitative/quantitative evaluations on how their technologies will:

  1. Achieve a quantum leap in productivity and product quality compared to the state-of-the art, for example by demonstrating substantial product recovery under gentler processing conditions or concurrent clearance of product- and process-related impurities.
  2. Reduce price tags by abating operational and capital costs, focusing on the cost of the adsorbents, usage of buffers and service lines, processing time, ability of the proposed technology to increase the number of processes and/or campaigns per year within a single biomanufacturing facility.
  3. Improve environmental sustainability by focusing on materials that are sourced and fabricated with lower life cycle impact, have a higher lifetime, and are recyclable.
  4. Accelerate process development and validation, for example by streamlining the integration with the up-stream segment and process analytical technologies, enabling single use or disposability, facilitating control and automation.
  5. Include advancements in multiple disciplines, for example by integrating molecular or systems-based modeling, material informatics, advanced fabrication and characterization techniques, computational fluid dynamics, data science, machine learning and artificial intelligence.

Oral session 7:   Separating without Sticking – Adventures in Non-Adsorptive Separations

Elizabeth Goodrich, MilliporeSigma
Caryn Heldt, Michigan Tech

While many non-adsorptive methods for separation and purification are well-proven in classical chemical and small molecule pharma processing, they are used in bioprocessing as an afterthought, if at all. There are some clear examples of non-adsorptive processes becoming standard in bioprocessing: final formulation was once completed by size-exclusion chromatography and is now typically an ultrafiltration/diafiltration step, and increased regulatory scrutiny of viral safety led to the implementation of parvovirus-retentive filters. But there is more than just filtration that could be utilized for purification.

We are extremely familiar with sticky chromatography processes, which have been optimized from decades of refinement and provide high resolution but face challenges, including high buffer usage, validation burden, packing consistency for beads, and low dynamic binding capacities for membranes and monoliths. Should these processes continue to be the primary tool in our recovery toolbox?

With the explosion of new therapeutic modalities in the pipeline and the need for even established mAb templates to undergo a paradigm shift towards intensification, it is time to dig into the possibilities offered by non-adsorptive methods. Industry and academia alike are exploring unique purification techniques, like precipitation, crystallization, novel filtration modalities, and aqueous two-phase extraction, among others. If we inject the same energy and focus into non-absorptive processes as we have for chromatography and the mAb platform, could we see the same leaps in performance, robustness, productivity, and regulatory acceptance of a broader portfolio of unit operations?

In this session, we invite talks from industry and academia exploring the evaluation, development, and implementation of non-adsorptive separation technologies applied to the purification of diverse biomolecule modalities. We will explore many aspects that are relevant to these processes, including scalability, regulatory considerations, sustainability, and cost of goods. We are also interested in investigations into suitability for continuous processing and the ability to platform the technology for multiple bioproducts. Only through creativity will we push through the current hurdles and bring novel therapeutics to patients.

Oral session 8:   Capers and Antics Across the Purification Process

Yinying Tao, Eli Lilly and Company
Thomas von Hirschheydt, Roche

This session aims to shed light on creative approaches to resolving purification challenges encountered within the context of overall integrated purification processes (I.e., from harvest to formulation or in more limited segments). Topics will encompass a wide range of biologic modalities, including monoclonal antibodies (mAbs), proteins, adeno-associated viruses (AAV), antisense oligonucleotides, and more. Purification is a critical step in therapeutic biologics bioprocessing, ensuring product safety, purity, and efficacy. However, it presents unique challenges that require innovative strategies, technologies, and collaborations to overcome.

We welcome contributions covering a broad spectrum of purification challenges and successes, including but not limited to:

  • Novel purification strategies. Examples of advancing a high productivity drug substance process through integrated continuous process implementation, intensified batch operations, or a hybrid approach, along with innovative process analytical technologies (PAT) for real-time monitoring and control. We also welcome other examples of innovative approaches to enable high concentration drug substance for subcutaneous administration.
  • Transition from mAbs to novel modalities. What are the similarities and differences in the overall development and manufacturing strategy for new modalities versus traditional mAb processes? What knowledge and best practices from the mAb world can be applied to new modalities? What new approaches and considerations are required to solve the unique challenges new modalities pose?
  • Root cause manufacturing processes analysis. Examples include but are not limited to leveraging modeling and artificial intelligence to identify and mitigate process-related impurities, troubleshooting purification failures and improving process robustness and/or purification efficiency.
  • Internal and external partner collaboration. Examples will showcase partnerships among discovery, development, and manufacturing to improve drug developability, from molecule design through to manufacturing process design. We also welcome successful contract manufacturing organizations (CMOs) collaboration case studies encompassing technology transfer and purification process scalability or lessons learned from successful cross-industry partnerships in purification development.

We look forward to receiving submissions detailing your bold, creative, and even unexpected solutions to purification challenges across the entire bioprocess. Your contributions and active participation in this exciting session will let us explore innovative strategies and solutions to enhance purification efficiency, product quality, and patient safety.

Oral session 9:   Manufacturing Control and PAT: Successful Implementation and Continuing Obstacles

Astrid Duerauer, BOKU & Austrian Centre of Industrial Biotechnology
Emily Schirmer, Catalent Pharma Solutions

The benefits of real-time monitoring, and ultimately model predictive control (MPC), for manufacturing processes have been recognized but are still not widely applied in the industry. ICH and FDA guidelines encouraging Quality by Design and real-time process monitoring approaches for biopharmaceutical production have been available for more than fifteen years. Still, most manufacturing processes are carried out in batch mode, with product quality analysis executed at discrete timepoints. This approach is time consuming, often causing the process to stop and only proceed once a test result becomes available from an in-process sample. This resulting delay may limit real-time adjustments to accommodate for inherent variability in biological processes.

Examples of PAT for multiple product quality attribute (PQA) monitoring and MPC of chromatography steps have emerged and are promising for implementation into manufacturing and development facilities. Mechanistic, data-driven and hybrid modelling have shown to have numerous use cases across both the manufacturing and process development spaces. Recently, these technologies have moved into downstream processing, where faster processing times and highly variable matrices present significant challenges.

New upcoming modalities such as VLPs, gene therapy vectors, or antisense oligonucleotides are testing the limits of conventional downstream processing, which has been optimized for proteins and antibodies. Even though technologies addressing challenges arising from these new modalities are available, commercial-scale formats have not been launched. Broad characterizations studies on these technologies have not matured to the point of antibody processes, and risk assessments and approaches to process control are nascent.

In this session we are specifically interested in technology, concepts, and case studies enabling and demonstrating the successful implementation of PAT strategies and control strategies for all systems, including new modalities. We seek contributions which highlight:

  • New analytical technologies developed for in-line and at-line measurements and scalability considerations
  • Approaches to address the multiple PQA monitoring often required in downstream processing
  • Facility designs and new materials addressing challenges during downstream processing of new modalities such as gene therapy vectors, cell therapy products or antisense oligonucleotide (ASOs)
  • Use of PAT in the control of continuous manufacturing processes
  • Case studies on the application of PAT tools for process control, for use in clinical and commercial manufacturing.

Oral session 10:   Instagram vs. reality: Challenges, surprises, and successes in fitting your perfect process into an imperfect manufacturing facility

Olga Paley, Takeda Pharmaceuticals
Brad Stanley, Biogen

As a community we seek to develop robust bioprocesses that consistently meet product quality and process performance targets and are designed with an eye toward economics and sustainability. Once established at small scale, processes must be transferred and scaled up for clinical and commercial manufacturing. Additionally, existing programs manufactured at production scale must sometimes be relocated to alternative facilities. In the best case, the receiving site may be highly flexible or already designed in a way that closely aligns with process needs. More often, we face expected or unexpected gaps requiring either thoughtful retrofits of these legacy facilities or last-minute modifications to our process design. These challenges may be magnified for new modalities that do not fit traditional mAb process paradigms or for proteins that have unique product quality challenges. Alongside the complexities of defining parameters that do not scale linearly, we may face surprises even where scaling is well understood. Tech transfer always carries with it inherent risks of unexpected performance differences or failure to meet material comparability acceptance criteria - both of which can put program timelines and potentially patient access at risk.

In this session, we will explore processes on the move and the creative approaches required to overcome manufacturing hurdles to deliver drugs to patients. We are looking to hear about smart or unusual strategies to transfer and scaling up, scaling out, or strategically scaling down and the application of digital tools in accomplishing the task. We are also open to stories about best laid plans for process transfer failing and the resulting lessons learned. We are especially interested in submissions that run the gamut of modality type (e.g., mAb, Fab, bi-specifics, GT, CT, ASO).

Once tech transfer has been successfully achieved and the manufacturing processes established, cumulative at-scale manufacturing experience can be a source of opportunities. This session looks to explore how such data can streamline future process development, especially for assets that are dissimilar, and how we can integrate learnings from transfers to build knowledge and align approaches between programs. This can include modeling based on historical at-scale data to drive decision-making and process integration as well as leveraging of AI and machine learning approaches to solve transfer, scale-up, or manufacturing challenges.

Oral session 11:   Innovative Purification Technologies

David Wood, Ohio State University
Brenda Carrillo-Conde, Pfizer

In this session we are interested in exploring the directions that companies and academic researchers are pursuing to develop new manufacturing technologies for the next phase of biopharmaceutical production. As the biologics industry continues to evolve and the market for mature products such as mAbs and vaccines becomes more competitive, companies are looking for ways to decrease cost and increase flexibility and efficiency while maintaining high quality. Additionally, as we move beyond traditional mAb formats, emerging new modalities such as mRNA vaccines and therapeutics, plasmids, cell and gene therapies, and more, have created new challenges that are not always readily solved with existing purification technologies and/or chemistries.

In many cases, these new technologies will be driven by advances in basic science that can enable selective separations based on innovative molecular or physical interactions, as well as novel strategies in process and ligand development. This session will evaluate the development and strengths of these technologies and will highlight the potential impacts of their future implementation on business, scientific, technological or unmet bioprocessing needs. Discussion on fundamental scientific insights leading to novel purification scientific and technology development is encouraged. Innovations in any relevant unit operations are appropriate, including harvest, chromatography, and membrane or other non-chromatographic processes, including new ligand design and surface chemistries.

Our goal is to assemble a session that spans diverse topical areas, ranging from new downstream processing formats, the application of high-throughput technology to support purification process development to the design of novel separation materials by the versatile exploitation of molecular properties. Of particular interest is enabling capabilities that have the potential to generate transformative and disruptive production platforms, similar to Protein A in monoclonal antibody downstream processing.

Poster Session

Ana Azevedo, Instituto Superior Tecnico
Glen Bolton, Amgen
Michaela Wendeler, AstraZeneca

In 2024, we are excited to venture out of the shadows of the pandemic and into the sun to pursue new adventures! As in previous years, the poster session will be a key part of the Recovery conference and is meant to provide a forum to showcase and discuss the best science and the most exciting advances our field has to offer.

We invite submissions that span the full breadth of challenges and solutions for downstream processing of diverse modalities. This includes fundamental research into bioprocessing, theoretical and computational techniques that are uniquely enabling for downstream operations, advances in downstream strategies for a wide diversity of established and emergent classes of biotherapeutics, and novel tools for process monitoring and control. We welcome case studies that illustrate process evolution from early stage through commercial development or discuss the regulatory and business decisions that precede process implementation. And finally, we invite contributions that present blue-sky concepts – novel ideas and strategies with the potential to revolutionize our field. We welcome submissions from academia, small and large companies, regulatory agencies, all geographical regions, junior and senior investigators etc.