This presentation will cover case studies from upstream, downstream, analytical and formulation development to support diverse modalities.

Explore practical and successful applications of analytics and AI in manufacturing across small, medium, and large enterprises in the U.S. Learn where to invest to start and sustain a digital transformation journey, drawing on research and best practices from MIT and McKinsey. Discover impactful uses of Generative AI currently shaping the industry that will drive future investment.

Data analytics has become an important tool in the development and manufacture of biopharma products and has delivered speed in development, cost-efficiency in manufacture and has added important new capabilities to process science.  Effective and successful implementation of data analytics into the business requires a strategic approach, clear goals and leadership buy-in.  Prioritization of investment and sustained effective change management are necessary to harvests the benefits of this technology.  A strategic, portfolio and network level view can maximise the realization of benefits. Enabling factors and potential barriers will be discussed and the results of a recent cross-company survey will be shared.  The potential impact of AI on the CMC environment will be discussed and examples of AI capabilities will be reviewed.

The biopharma industry is poised to be transformed by deep-learning physical science models. These new AI tools are clearly powerful and entire companies have spun up around their capabilities, particularly in drug discovery. However, their use in process development poses some challenges around model training, validation, and accuracy. Limited datasets, incomplete model “exercising”, lack of appropriate controls, and complex non-linear behaviors all need to be considered and addressed - particularly as the application of the technology gets closer to filings and control uses. This presentation will flesh out some of those technical challenges, and how they might be mitigated by changes in staffing and directed skills development.

The demand for greater reliability, efficiency, agility, and differentiation in biopharmaceutical development necessitates leveraging artificial intelligence (AI) and machine learning (ML) technologies. At Amgen, we are developing AI/ML-driven solutions that integrate advanced data analytics and in silico modeling to enhance drug substance process development and manufacturing. Our approach centers on embedding machine learning models across the biopharmaceutical lifecycle, from cell line development to process optimization and manufacturing.

Biological systems' inherent complexity—characterized by unknown mechanisms and parametric uncertainties—challenges the application of a single modeling strategy across development stages. To address this, we present three case studies demonstrating the transformative potential of ML models in biopharmaceutical processes: In the first case study, we demonstrate our internally developed ML models for cell line development to predict high-performing clones with increased precision and to shorten experimental timelines while reducing resource requirements. In the second case study, we demonstrate ML digital twins to uncover complex or unknown mechanisms in cell culture enabling in silico exploration of design spaces. These models will allow rapid evaluation of media compositions and feeding strategies to maximize productivity while maintaining product quality. Finally, a newly developed product quality model supports manufacturing process consistency by correlating process variables with critical quality attributes—such as glycan profiles and charge variants— derisking process optimization implementation strategies while maintaining essential quality parameters.

Collectively, these innovations highlight a transformative digital capability that addresses industry-wide challenges. By automating data analysis and accelerating process design our AI/ML initiative provides Amgen with a sustainable competitive edge and sets a benchmark for future advancements in biopharmaceutical manufacturing.

The biopharmaceutical industry faces growing pressure to accelerate the development of new therapeutics while reducing production costs and ensuring product quality at scale. Despite advancements in cell line development, the traditional upstream bioprocessing workflows remain slow, repetitive and highly resource-intensive. These challenges contribute to long development timelines and low data throughput, making bioprocessing a critical bottleneck during R&D and production scale-up. Pow.bio has developed an intelligent continuous bioprocessing platform that addresses these limitations by significantly increasing the speed of bioprocess development. Our system enables rapid optimization of bioprocess conditions and generates data 5–10 times faster than the traditional processes. We developed real-time digital twin software, which predicts system outcomes, automatically detects abnormalities, and dynamically adapts process parameters to constantly search for the bioprocess optimum. This adaptive control approach improves both process reliability and volumetric productivity by enabling faster optimization cycles and reducing batch failures caused by suboptimal conditions. In a case study demonstrated in functional protein production with Pichia pastoris, our platform achieved nearly double the volumetric productivity compared to the baseline process. By accelerating bioprocess data generation velocity and increasing productivity, our approach aims to fundamentally reshape biomanufacturing and contribute to a more sustainable and efficient future for the bioeconomy.

Digital and computational technologies are still underleveraged in pharmaceutical manufacturing when benchmarked against semiconductors, petrochemicals, and energy, or even in comparison with other regulated industries such as automotive or aerospace. Given increasing cost and timeline pressures faced by the pharmaceutical industry, digital tools—both mechanistic and data-driven—become even more indispensable to achieve efficiency (cost savings), robustness, and acceleration during commercialization and technology transfers of new drug assets. 

Through case studies focused on large molecules, we demonstrate how digital tools are poised to realize Industry 4.0 principles of digitally-enabled development and manufacturing. We highlight how mechanistic models and data-driven ML/AI techniques, even at earlier stages of maturity, realize value for the business. Computational fluid dynamics (CFD), a mature modeling tool, has consistently been used replace at-scale mixing studies and reduce technology-transfer costs associated with expensive engineering batches. Lyophilization is another mature modeling practice used routinely to design process cycles and de-risk technology transfers across sites. Plant modeling using flowsheet models is an emerging technique to support commercialization—these models can be used to explore design choices and define control strategy, among a variety of other applications. (Indeed, flowsheet models are deeply embedded in the petrochemicals industry but remain underutilized in pharma.) Finally, bioreactors present a greater modeling challenge, but also offer the greatest value proposition as bioreactors are central to all bioprocesses. We share an emerging hybrid modeling approach wherein mechanistic bioreactor kinetic models are bolstered with data-driven ML/ANN (machine learning/ artificial neural network) kernels that learn the metabolic behavior of cells. This hybrid mechanistic/ML approach greatly improves the predictability of the bioreactor model, which renders the model suitable for in-silico process characterization and setting the foundation for real-time process control of bioreactors in future. These examples are intended to demonstrate not only current progress, but also highlight future possibilities for advancing digital tools in (bio)pharmaceutical manufacturing, including leveraging Generative AI and large language models (LLMs) for knowledge management. We hope to encourage further investments in the industry towards digital/modeling and secure broader acceptance from regulatory agencies. 

Development of biopharmaceuticals is lengthy and with the recent speed of innovation, has the risk of losing value for patients if not delivered with speed. With the growth in digital platforms and ability to harness data, the concept of a “development digital twin” can be envisioned where connecting the blocks in the development process through digital and data could buy speed with rigor. This requires an end to end thinking and build up of predictive models that enable decision making. In an attempt to chain those pieces together, the presentation will exemplify a connected stream of models that can drive not just speed but rigor, fundamental understanding, and controls during product development. Leveraging digital solutions to enhance speed, gain standardization and ensuring data integrity during device development and submissions will also be explored.

Traditional biopharmaceutical production relies on one-size-fits-all expression vectors and iterative, empirical process optimization. This standard approach limits productivity and performance, hindering the commercial viability of increasingly complex modalities by causing development hurdles and extending time to clinic.

In this talk, we present a vision for the future of biopharmaceutical development, and discuss our progress toward end-to-end design of genetic systems, cell lines, and bioprocesses using a portfolio of mechanistic, AI-based, and hybrid models. We highlight case studies that demonstrate the power of this approach across multiple modalities, including monoclonal antibodies and viral vectors.

Many biotherapeutics require administration of high doses to achieve optimal efficacy, and while advances in drug substance manufacturing have enabled production of high quantities of therapeutic proteins, drug product formulation has been constrained by high viscosities at concentrations exceeding ~ 150 mg/mL.  Consequently, administration of high doses (>500 mg/dose) often require intravenous approaches.  The high cost of clinical administration as well as patient inconvenience (need to travel to the clinic, infusions taking several hours, etc.) present significant compliance challenges.  A number of formulation approaches which do not rely on aqueous solutions have emerged recently, as many pharmaceutical companies aspire to transition their products to subcutaneous administration.  Elektrofi’s protein microparticle suspension process uses standard manufacturing equipment and reagents to enable concentrations >500 mg/mL, and as such can deliver a 1 g dose in a 2 mL subcutaneous injection (which can be administered in under 15 seconds); larger doses are possible and compatibility with autoinjectors and on-body devices has been demonstrated.  The feasibility of Elektrofi’s innovative approach has been established for over 20 proteins (mostly mAbs), with PK/PD profiles similar to an aqueous subcutaneous comparator, and comparable immunogenicity trends demonstrated in animal models.  Another benefit of Hypercon™ technology is enhanced stability relative to aqueous formulations: stability of Elektrofi’s microparticle suspensions tends to be comparable to lyophilized products, and Hypercon™ products are ready to use and do not require reconstitution.  Elektrofi is establishing a GMP-ready process for production of clinical supplies at a CDMO.  Once the platform process is implemented, multiple products will be able to benefit from this approach.  While initial clinical trials for approved products switching to a Hypercon™ formulation are expected to include an efficacy arm, preliminary discussions with regulators indicate that eventually this formulation change can be considered as lifecycle management, requiring only a bioequivalence study like that for a biosimilar.  Consequently, this formulation approach is likely to provide a rapid pathway for implementing subcutaneous options for biotherapeutics requiring high concentrations.

This talk will explore the advancements in high-volume subcutaneous (SC) drug formulations, which have revolutionized complex therapy administration by transitioning from intravenous (IV) infusions to more convenient SC injections. Focusing on the development and launch of two high-volume SC formulations, we emphasize using platform excipients and avoiding complex delivery mechanisms or novel components. Key strategies will address solubility, stability, and minimizing changes from the original formulations to accelerate development and mitigate late-stage challenges. Real-world case studies will illustrate the impact of these innovations on patient experience and healthcare outcomes.

Monoclonal antibodies (mAbs) provide unparalleled specificity and therapeutic potential; however, their high-dose requirements (>10 mg/kg) necessitate intravenous (IV) delivery. IV delivery imposes a substantial burden on patients and the healthcare system, limiting patient quality of life and straining hospital resources. Subcutaneous (subQ) administration offers a patient-centric alternative, but current subQ formulations are constrained by low concentration limits (<150 mg/mL), requiring large injection volumes and extended administration times, often necessitating external pumps or trained personnel. AcousticaBio has developed a proprietary formulation technology to revolutionize the delivery of biologics. Featuring ultra-high concentration subQ delivery of mAbs (>500 mg/mL) compatible with standard subQ syringes, it enables mAbs to be reformulated into small-volume, quick injections that patients could self-administer in the comfort of their homes. By leveraging Harvard-patented technology – namely acoustophoretic printing - AcousticaBio uses airborne ultrasound to engineer hydrogel-mAbs microparticles in a process that is a solvent-free, drying-free process. AcousticaBio’s manufacturing platform is a “one-size-fits-all” solution that, by eliminating molecular degradation risks associated with organic solvents and air-interface stress, ensures superior stability, consistency, and traceability. Notably, it can be readily applied to vitually all antibodies with minimal formulation changes. AcousticaBio has validated its approach both in-vivo and in-vitro, with several commercial antibodies, and has demonstrated safety, high bioavailability, and standard pharmacokinetic profiles. These formulations are easily injectable, requiring minimal plunger force (<20N) with standard 25-27G needles. Additionally, the sterile production process ensures readiness for in-vivo applications and long-term stability studies. Using GRAS and GMP-grade materials, AcousticaBio’s workflow has been tested with several biotech companies and federal agencies, successfully reformulating mAbs from low-concentration solutions (15-30 mg/mL) to ultra-high formulations (>500 mg/mL). AcousticaBio is excited to support the biotherapeutic industry to enhance patient access and quality of life while reducing healthcare burdens.

The subcutaneous administration of biologics is rapidly gaining traction as a compelling alternative to intravenous (IV) administration across various disease areas. This shift is evidenced by a growing number of biologics administered subcutaneously. Despite its advantages, subcutaneous administration presents unique formulation, process, and delivery challenges. These challenges must be meticulously managed through the development of high-concentration formulations that maintain the injectability of biologics with manageable viscosity and appropriate injection volumes. This talk will offer an in-depth overview of the primary obstacles encountered in subcutaneous biologic administration. Following this, two case studies will be presented, illustrating product development from the perspectives of formulation, process, and container closure challenges. Attendees will gain valuable insights into the complexities and solutions associated with subcutaneous biologic formulations, ensuring their effective and safe administration.

Two recent trends, growth in novel modalities and increased shift towards SC administration, are challenging the ability of biopharmaceutical development community to deliver patient centric products with rigor and speed. One of the levers that has been widely used to enable that is the use of platforms and alignment on standards/ guidance. However, to build such platforms a rigorous understanding of the system is required which then feeds the control strategy and eventually platform success. In this presentation, such opportunities across the drug product and device space will be discussed and exemplified.

Developing large-volume parenteral products for s.c. delivery poses significant challenges. Innovations in injector devices now allow delivery volumes exceeding 15mL, offering patients the convenience of at-home self-administration. However, this progress brings complexities that demand a deep understanding of the drug’s molecular behavior, its interactions with the primary packaging, and its delivery using advanced devices. Formulating high-concentration biologics for s.c. delivery is one of the key hurdles. These formulations must maintain stability, sterility, and efficacy without compromising product quality. Selecting suitable primary containers that ensure compatibility and prevent degradation throughout the drug’s lifecycle adds another layer of difficulty. Seamless integration of the drug product with advanced injector devices is paramount to ensure safe delivery, optimal performance, and patient safety. Collaboration with device manufacturers is essential to overcome these design and compatibility challenges. From prototype development to final product approval, strong partnerships ensure alignment between drug product formulation and device design. Regulating combination products introduces further complexity, with stringent guidelines governing these therapies. Compliance with these regulations requires strategic alignment among drug developers, device engineers, manufacturers, and health authorities. Accelerating large-volume s.c. delivery programs demands a holistic approach. This includes streamlining development timelines through iterative testing, leveraging advanced analytical tools, and fostering efficient communication between all stakeholders. This integrated approach balances innovation with safety and regulatory demands. Ultimately, advancements in large-volume parenteral delivery open the door to accessible, patient-friendly treatments. By addressing the formulation, packaging, and design challenges through collaboration and adopting efficient strategies, the industry can continue to innovate while maintaining the highest standards of quality and safety. This comprehensive approach ensures accelerated yet robust development timelines, paving the way for groundbreaking therapies that transform patient care.

After the fold

CMC becomes increasingly important with the emergence of artificial intelligence aided by mega databases and convenience demanded by end users. CMC acceleration is a must now accompanied with an acceleration in discovery, and therapeutic companies with various resources and timelines. A drug product not only is the final Stock Keeping Unit (SKU) delivered to clinicians but reflection of a concentrated effort from drug substance, drug product development and manufacturing across all modalities. 

High concentration up to hundreds of mg/mL and low concentration down to g/mL are in demand based on modalities and final administration routes. Subcutaneous delivery is a preferred administration route than IV, such an administration placed much higher requirements on CMC development, manufacturing and devices integrated. As a CRDMO, the mission is to enable innovative companies in terms of flexibility, timeline, cost and quality. Acceleration of timeline provides that flexibility while ensuring cost effectiveness and quality to the innovative companies. Acceleration comes from efficiency which comes from 1st hand experiences, databases, automations and real time collaborations. An integrated effort including acceleration from all functional groups that achieving from DNA to IND in 6 months will be showcased in this presentation. Formulation knowledge from scientists and mega databases followed by manufacturing capabilities and capacities are the foundation for early-stage products, devices when administered subcutaneously guided ISO 11608 builds onto that foundation when early-stage products become late stage, thus integration of formulation, manufacturing and devices are essential for CRDMOs to achieve its timeline acceleration mission. Efficiency gaining from databases and AI has already taken place, expected to continue across all modalities to meet target product profiles defined by the innovative companies.    

Small cell lung cancer (SCLC) is a fast-growing, aggressive disease with poor treatment outcomes. Over the last few decades, advances in the treatment of SCLC have been incremental, and the 5-year survival rate has remained around five percent. To approach this challenge, we developed IMDELLTRA® (tarlatamab-dlle), a bispecific T-cell engager (BiTE®) molecule targeting delta-like ligand 3 (DLL3). DLL3 is a noncanonical Notch family ligand that is involved in neuroendocrine cell development and that localizes to the cell surface selectively in SCLC tumor cells. BiTE technology provides a targeted immunotherapy approach that is independent of peptide MHC expression or the presence of specific T cell clones. Tarlatamab is designed to bind cell surface DLL3 and CD3 expressed on the surface of T cells, resulting in redirected lysis of SCLC cells by activated T cells. 

In preclinical models of SCLC, tarlatamab induced tumor regression and completely cleared metastatic tumor lesions. In the first-in-human clinical study in patients with relapsed or refractory SCLC, tarlatamab monotherapy was well tolerated and induced objective antitumor responses. A phase 2 clinical study demonstrated a 40% objective response rate with median overall survival of 15.2 months for the 10 mg tarlatamab dose. These data led to the accelerated approval of tarlatamab on May 16, 2024, for the treatment of patients with extensive-stage SCLC patients who progress on or after platinum-based chemotherapy. The next month, IMDELLTRA® was added to the National Comprehensive Cancer Network guidelines for SCLC treatment in the second-line setting, highlighting its impact for patients. IMDELLTRA® continues to be evaluated in additional clinical studies to assess its potential in earlier stages of SCLC and lines of therapy as well as in combination with standard of care agents. 

At Amgen, our mission is to deliver high-quality, innovative medicines to meet the needs of patients with serious diseases. Beyond developing these therapies, we are dedicated to achieving our sustainability goals by minimizing our environmental impact across our global operations. Amgen Ecovation™ embodies our commitment to innovative and sustainable manufacturing and process development, which we integrate into the design, development, and execution of all new laboratories and manufacturing facilities.

To achieve these objectives, our process development teams have concentrated on implementing intensified drug substance processes. These efforts have resulted in industry-leading productivity, increasing the drug substance mass produced per run, reducing the number of batches required for each program, and decreasing the scale of the runs needed. Additionally, the implementation of these intensified processes has not only improved drug substance output but also reinforced our commitment to sustainability.

Moreover, we have integrated aspects of Industry 4.0 into our manufacturing and process development workflows. This includes the use of in-silico modeling to reduce the number of lab-based experiments and the incorporation of high-throughput automated equipment 

Despite commitments to ambitious greenhouse gas reduction targets, many biomanufacturers continue to face significant challenges in addressing their Scope 3 emissions. These value chain emissions are complex, persistent, and often difficult to measure. This presentation examines how integrating ecodesign principles with data transparency can overcome these hurdles and drive measurable reductions in greenhouse gas emissions. Ecodesign focuses on embedding sustainability into product and process development, reducing resource consumption, energy demands, and waste across the lifecycle. Meanwhile, data transparency sheds light on Scope 3 emission hotspots, enabling organizations to make informed decisions, monitor progress, and foster greater accountability. Through case studies and actionable strategies from Cytiva’s sustainability initiatives, this session demonstrates how these complementary approaches can decarbonize bioprocessing operations, enhance supply chain collaboration, and support the achievement of ambitious sustainability objectives.

Manufacture of parenteral biological products, which can be susceptible to microbial contamination, include prevention and detection controls to ensure product quality and patient safety. Next to microbial contamination of the product, the presence of pyrogens poses a substantial risk to patients. The compendial rabbit pyrogen test (RPT) is a method to detect pyrogens, a chemically heterogeneous group of fever-inducing compounds of microbial and non-microbial origin. The compendial bacterial endotoxin test (BET) to measure endotoxin, a cell wall component of Gram negative bacteria, relies on a reagent derived from horseshoe crab blood (limulus amoebocyte lysate; LAL). In accordance with 3R principle for animal welfare, there is a need to adopt methods that do not rely on animal testing and animal-derived components. The monocyte activation test (MAT) and recombinant Factor C (rFC) are sustainable test methods for pyrogen and endotoxin testing, respectively. The challenges in making the switch to sustainable test methods include uncertainty regarding method validation requirements for global regulatory acceptance. Health authorities are taking the next steps to move away from animal testing or the use of animal-sourced reagents by revising applicable pharmacopoeia guidelines. The European Pharmacopoeia is in the process of removing the RPT from 57 pharmacopeial monographs and inclusion of a new general chapter on Pyrogenicity (5.1.13). Ph. Eur. 2.6.30 Monocyte Activation Test is recognized as a suitable in vitro test for pyrogens since more than a decade and Ph. Eur. 2.6.32 Test for Bacterial Endotoxins using Recombinant Factor C has been effective since 2021. USP<86> Bacterial Endotoxins Test Using Recombinant Reagents, which will become official in May 2025, also describes how to use non-animal-derived reagents for endotoxin testing. This presentation will provide an overview of sustainability efforts for Health Authority acceptance: Replacement of in vivo RPT with in vitro MAT Replacement of LAL-based BET with rFC-based BET

The integration of Continuous Chromatography with on-demand inline Buffer Blending presents a transformative sustainability solution for biomanufacturing. This innovative approach boosts process efficiency, reduces resource consumption, and lowers operational costs. By enabling continuous purification and on-demand buffer preparation, it minimizes buffer storage, waste, and energy use. This advanced system not only reduces environmental impact but also optimizes resource utilization by cutting water, buffer, and energy consumption. Transitioning from traditional batch processes to continuous workflows enhances scalability, throughput, and cost efficiency. Eliminating reliance on single-use plastic totes and disposable tubing sets for buffer storage and movement further cuts plastic waste, simplifies workflows, and reduces labor demands. Data will be presented to show aggregated savings resulting from smaller facility footprint and resultant reduced capital and operating cost along with reduced personnel, energy consumption and plastic waste all provide a compelling case for adoption of Combined and integrated Continuous Chromatography Systems and Inline Buffer Blending. This technology not only supports corporate sustainability goals but also positions manufacturers for long-term success in a marketplace increasingly driven by environmental responsibility. It’s a high-impact, cost-effective solution that combines operational excellence with a reduced footprint—ensuring economic and ecological value for the future of bioprocessing.

Biopharmaceuticals play an important role in offering life-saving solutions to patients with critical diseases like cancer. Beyond their significant health benefits, they are also a key driver of economic growth, with the market rapidly approaching the trillion-dollar mark. The adoption of environmentally friendly production practices is, therefore, needed to ensure the balance of the social, economic, and environmental pillars of sustainability. However, measuring environmental performance can be a daunting and data-intensive task, particularly for non-experts. To encourage broader adoption of sustainable practices and enhance industry accountability, it is essential to identify critical process factors and assess them using fair, comprehensive, and simple indicators.

The biopharmaceutical industry increasingly relies on microbial biosynthetic factories for producing biologics due to their scalability and versatility. However, the economic efficiency of these processes is often limited by the rapid exhaustion of microbial cells, which lose productivity or die under the metabolic burden of product synthesis. This results in frequent bioreactor restarts, increased costs, and inefficiencies. AsimicA’s patented Microbial Stem Cell Technology (MiST) introduces a novel solution inspired by multicellular regeneration. MiST enables microbes to divide asymmetrically, creating two distinct cell types: stem cells, which maintain culture viability, and factory cells, which maximize product synthesis. This continuous regeneration of productive cells allows the culture to sustain high productivity over extended periods. In laboratory trials, MiST cultures demonstrated a threefold increase in protein production compared to conventional microbial systems. The technology’s regenerative mechanism not only boosts yields but also reduces operational costs and waste, aligning with the industry’s sustainability goals. MiST can be applied across a wide range of biologics, offering transformative potential for biopharmaceutical manufacturing.