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

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)

This presentation will focus on the technical and manufacturing capabilities for cell therapy commercialization with discussion of CMC requirements, manufacturing launch readiness, and supply considerations. Specific considerations for a cell therapy and partnership with contract manufacturing organizations will also be discussed including lessons learned.

IMPT-314 and IMPT-514 are autologous CAR T products that use the same CD19/CD20 bispecific tandem CAR, and the same cell manufacturing process selecting for desirable naïve/memory T cells. The process was developed by Professor Yvonne Chen at UCLA and was successfully transferred to ImmPACT Bio, a clinical-stage biotech company.

IMPT-314 is being studied in a Phase 1/2 clinical trial in aggressive B cell lymphoma. IMPT-514 is being studied in a Phase 1/2 clinical trial in lupus nephritis and systemic lupus erythematosus. Both trials are actively enrolling patients.

While the efficacy and durability of autologous CAR T therapies remain unparalleled, a key challenge for scalability and continued adoption is the high cost of manufacturing. Constrained by single patient batch manufacturing, resource-intensive manual processes with open steps, these therapies require highly skilled direct labor, expensive GMP cleanroom infrastructure and controls, with limited opportunities for scale-up.

We present a case study of transition from an established GMP manual process to an automated, closed-processing manufacturing platform, and address the following topics:

• Selection of automated platforms
• Process development and product comparability,
• Converting GMP operations to automated & paperless systems,
• Benefits and challenges of automation,
• Aligning manufacturing process changes with clinical development phases.

Learn how to define tech transfer and distinguish between standard and customized approaches and workflow. Brandon Haigh, an experienced cell therapy process development scientist, will share eight common pitfalls to avoid during any tech transfer. He will als provide insight into seven unique challenges faced by cell therapies and conclude with six key take-aways.

Increasing demand for recombinant adeno-associated virus (rAAV) based gene therapies necessitates increased manufacturing production. Transient transfection of mammalian cells remains the most commonly used method to produce clinical-grade rAAVs due to its ease of implementation. However, transient transfection processes are often characterized by sub-optimal yields and low fractions of filled-to-total capsids, both of which contribute to the high cost of goods of many rAAV-based gene therapies. Analysis of our previously developed mechanistic model for rAAV2/5 production suggested that the inadequate capsid filling is due to a temporal misalignment between viral DNA replication and capsid synthesis within the cells and the repression of later phase capsid formation by Rep proteins. We experimentally validated this prediction and showed that performing multiple, time-separated doses of plasmid increases the production of rAAV. In this study, we utilize the insights generated by our mechanistic model to develop an intensified process for rAAV production that combines continuous perfusion, high cell density transfection, and re-transfection which resulted in increased titer and plasmid efficiency. Our results establish a new paradigm for continuously manufacturing rAAV via transient transfection that improves productivity and reduces manufacturing costs.

AAV has emerged as a significant therapeutic modality in gene therapy. Challenges such as poor yield and variable product quality persist in the viral vector manufacturing space and we have addressed these problems using our cell engineering technology. Our cell engineering platform for improved adeno-associated virus (AAV) manufacturing addresses the critical challenges in gene therapy manufacturing, and presents an innovative modality for improving cells for production of viral vector therapeutics. Our platform, yielding cells with improved AAV production and CQAs, can significantly bolster the efficiency and cost-effectiveness of gene therapy manufacturing, and can accelerate current development timelines. We used a directed-evolution approach based on repeated cell fusions to shuffle the cell genome, and amplify chromosomes of HEK-293 host cells. Engineered clones enriched for mitochondria phenotypes were isolated, then used as transient-transfection hosts, and for creating stable packaging and producer cell lines. For generation of stable packaging and producer cell lines, we developed a novel inducible system that maximizes the capabilities of the inherent viral production machinery. Engineered HEK-293 clones grown in suspension culture exhibited up to 15-fold productivity improvement via triple transient transfection for AAV1, AAV2, AAV5, and AAV9 serotypes with capsid titers as high as 1017 viral particles/L (vp/L)—at least 10-fold higher than current industrial manufacturing processes. Selection for certain mitochondria phenotypes resulted in a 2-fold improvement in full-to-empty ratio—up to 55% full in crude supernatants. Finally, our engineered stable packaging and producer cell lines achieved capsid titers of up to 1016 vp/L. We demonstrated a multi-modal cell-engineering platform that has significantly improved yield and manufacturability for transient transfection and for stable packaging and producer cell line methods. We further propose a model regarding the role of mitochondria for enhancing capsid percent-full. Taken together, our disruptive platform technologies provide solutions for meeting current—and future—gene therapy manufacturing challenges.

• 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)

With the RoSS.FILL CGT system, Single Use Support delivers unprecedented filling accuracy for aseptic aliquoting of advanced therapies into single-use bags. Dive into state-of-the-art, scalable ATMP fluid management with 21 CFR Part 11 reproducible accuracy.

This brief presentation will discuss an alternative photon source, X-ray. We will examine the similarities and differences between gamma and X-ray and why X-ray is an ideal alternative or addition to meet and secure these critical needs for bioprocessing systems. X-ray is supported by peer-reviewed publications, available seminars/webinars, and technical support globally. Although X-ray has been known for decades as just like gamma and E-beam, its limitation just has not been needed or easily available, so we want to also update global expansions including in the US with the opening of a production scale system in our Libertyville IL facility, making not just testing but production quantities possible.

Ensuring viral safety is essential in the development of biopharmaceutical products. With the recent updates to ICH Q5A, it is crucial to assess the ability of your manufacturing process to remove viruses. This talk offers strategies for optimizing your viral clearance studies for various product types.

Addressing challenges like identifying high-performance media and optimizing scalable processes, Lonza CHO media portfolio, including TheraPRO^®, streamlines media screening and optimization for commercially available CHO cell lines. Achieve high titer and superior scalability with our globally harmonized, regulatory-compliant manufacturing facilities, enabling a seamless transition from research to commercial manufacturing.

In this presentation, a direct comparison will be established between the FUNDALOOP® and current state-of-the-art harvesting techniques. Advantages and disadvantages will be discussed, and it will be shown that the FUNDALOOP® outscores by a landslide, leading to a very promising future of cell harvest as a whole.

• 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

Automation plays a key role in improving the quality and lowering the cost of cell therapy products. As new or improved processing and testing technologies enter the market, it’s important for firms that build these products to design and provide both digital and physical integration touchpoints for their systems and consumables. This overview will discuss some of these important design considerations that will allow for more effective implementation of automation and make it easier to adopt new technologies.

Explore our other tracks to curate your ideal conference experience, and discover exciting new content that sparks your curiosity!

Ultragenyx is developing an investigational gene therapy, UX701, an adeno-associated viral vector-based gene therapy product, for the treatment of Wilson disease. UX701 is an investigational AAV9 gene therapy designed to deliver a modified form of the ATP7B gene. Ultragenyx has initiated Cyprus2+, a seamless Phase 1/2/3 study of a single intravenous infusion of UX701 in Wilson disease (NCT04884815). UX701 leverages Ultragenyx’s proprietary producer cell line platform, Pinnacle PCL™. This presentation reviews our first late-stage development activities for our upstream Pinnacle PCL™ platform process including parameter risk assessment, scale-down model qualification, and process characterization, to establish process controls for the upstream unit operations in our 2000L manufacturing process. The process characterization studies help us understand our parameter space and mitigate operational and quality risks which are critical for successful implementation of a robust commercial manufacturing process to provide consistent product quality throughout the product’s lifecycle.

Recombinant adeno-associated virus (AAV) as a delivery method for gene therapy continues to be successful with more than a hundred ongoing clinical trials globally and some recent approvals. The AAV purity in the final drug product remains as an area of focus in the field, particularly the relative amount of full viral particles, and anion exchange chromatography (AEX) is one of the most common and scalable approaches used for that purpose. The focus of this presentation will be on the development and optimization of a full capsid enrichment step using POROSTM AEX resins. The case study will showcase a scalable purification method that meets typical purity targets for AAV therapies.

This presentation delves into the critical aspects of late-stage characterization for antibody-drug conjugates (ADCs) and their role in a robust analytical control strategy essential for successful marketing applications. Starting with an explanation of product characterization and its necessity, we outline its integration into the control strategy, highlighting its role from preclinical development through to commercial production.

Key topics include:

1.Product Characterization: Importance, steps, and impact on safety, efficacy, stability, and performance.

2.Control Strategy Integration: How characterization supports the Quality Target Product Profile (QTPP) and defines critical quality attributes (CQAs).

3.Case Study: An ADC characterization project at KBI Biopharma, showcasing methodologies, challenges, and data analysis.

This presentation emphasizes the essential role of comprehensive characterization in ensuring ADCs meet regulatory standards and therapeutic goals for patients with critical needs.

Analytical bottlenecks in bioprocessing result in the product being stalled between unit operations. Routinely these critical tests are not performed, creating process blind spots. Utilizing High Precision Tunable Laser Spectroscopy (HPTLS), we demonstrate how this rapid, quantitative analytical tool can be used to de-bottleneck and remove blind spots in bioprocessing.

As a CDMO, elite science and cutting-edge facilities are essential, but Bionova also believes a flexible, customer-first institutional mindset is equally important. Sometimes, this means creatively scoping projects to fit unique circumstances. Other times it means nimbly adding new capabilities to meet emerging needs. In all cases, it leads to better outcomes for partners.

Wheeler Bio has invested in best-in-class technology development to design, build and prove our process and analytical platform for antibodies; called Portable CMC®. This presentation will provide:

• An overview of the Portable CMC® design and build phase, including proof of the platform via manufacturing scale-up.
• A description of Wheeler's modular CMC development approach that more efficiently connects discovery, CMC, clinical, and capital.
• An overview of how we designed, built, and commissioned our clinical facility-of-the-future to meet our clients need for CGMP clinical supply.

Utilizing the optimal strain of E.Coli helps assure high quality nucleic acid production suitable for viral vector, mRNA, and other therapeutic applications. This presentation will showcase recent innovations and real lessons learned from decades of first-hand experience in pDNA, mRNA and LNP process development and manufacturing.

• What contributes to fostering a truly inclusive work environment?
• Building and sustaining a truly inclusive workplace
• Why is there more focus on DE&I- what is contributing?
• Adopting employee-focused innovative initiatives
• While multinational pharma companies like these are devoting more resources to diversity and inclusion initiatives internally, what impact will this have more widely?
• Why diversity in pharma leadership matters
• What is driving DE&I for talent today?
• Continual education: Regular training sessions on unconscious bias, cultural sensitivity, and the importance of D&I for all employees.
• Embracing D&I will not only lead to a more inclusive industry but also a more prosperous and innovative one.

• How can early-stage/research professionals best prepare for GMP Success?
  • Proactive strategies for early-stage researchers to navigate the transition to GMP and avoid common pitfalls
  • Drug substance, characterization/analytical, and generalist perspectives
• Critical Considerations for Development to Commercial Manufacturing Transition
  • Critical aspects beyond technical factors: commercial viability and managing COGs and CMC.
• Lessons Learned from Experience
  • Real-world examples, challenges, and key takeaways from transitioning projects to GMP manufacturing.
• Fostering Collaboration & Preventing Bottlenecks
  • The importance of cross-team collaboration and proactive strategies to identify and address potential issues early in development.

• Success stories: Meet 4 Latino leaders in Biotech
• In which ways have Latinos contributed to the Biotech industry?
• What are the consequences of years of limited diversity in the Biotech workforce?
• How lack of diversity might stifle innovation
• How can Latinos in the industry contribute to Health Equity?
• Why does diversity in general matter in Biotech?