Cambridge Healthtech Instituteの第10回年次会議
Accelerating Analytical Development
2023年8月16 - 17日、EDT（米国東部標準時）
Registration and Morning Coffee7:30 am
KEYNOTE PRESENTATION: How to Align the Definition of “Compendial Method” with Speed of Innovation?
Novel manufacturing platforms may have regulatory challenges for the analytical strategy as often regulations and guidance are developed and optimized for traditional platforms. The speed for the development of next-generation technologies is significantly faster than the updating compendial methodology in guidance and regulations. Current talk will challenge the definition of “compendial method” in modern-day environment in order to pave the way to propel the innovation implementation.
PLATFORMS & WORKFLOWS FOR NOVEL MODALITIES
Dual-Detection Approach for Charge Variant Analysis of Monoclonal Antibody Combination Products Using Imaged Capillary Isoelectric Focusing
We report a novel methodology to accurately quantify charge variants of monoclonal antibody mixtures that span 40-fold in ratio. With the wide concentration ranges of combination products, one component may fall within the linear range while the other does not. Imaged capillary isoelectric focusing conjugated with the multiple detection techniques allowed us to overcome this challenge.
Middle-Up Analysis of Alternative-Format Molecules Using New MS Strategies
Alternative-format biopharmaceuticals which feature domains linked by (Gly4Ser)n linkers provide new therapeutic opportunities through potentially enhanced binding properties. However, characterization of the intermolecular domain interactions that give rise to oligomeric species remains challenging, due to the variety of possible interaction interfaces at the subdomain level. In this study, we present an online, middle-up LC-MS-based method to characterize covalent and non-covalent subdomain interactions in alternative format drug substances.
Coffee Break in the Exhibit Hall with Poster Viewing10:00 am
OVERCOMING THE ANALYTICAL BOTTLENECKS FOR AAVs
Overcoming Analytical Challenges to Expedite Gene Therapy Development
Gene therapy products have demonstrated great potential for treating devastating diseases and are being extensively evaluated in clinical trials for many disease indications. The structural and biological properties of these products are complex and yet to be fully understood. Analytics are key to developing safe and efficacious products. Strategies to overcome analytical challenges to ensure the highest product quality and consistency in gene therapy development will be presented.
Analysis of Critical Quality Attributes for AAV Products Using Mass Spectrometry
Adeno-associated virus (AAV) has emerged as one of the most used vectors for gene therapy. Many structural features of AAV particles such as empty/full ratio, stoichiometry of capsid viral proteins, post-translational modifications of the viral proteins, as well as the residual host cell proteins and viral proteins are considered potential critical quality attributes (CQA). Characterization and quantitation of these CQAs using mass spectrometry techniques will be discussed in this presentation.
Improving the Throughput of a Very Low Throughput Method (CE-SDS) for Purity Analysis of mAb and AAV Samples
CE-SDS is a widely recognized platform technology for purity determination and impurity characterization in protein and gene therapy products. One of the major limitations of this method is its low throughput. Method development and optimization, and application of CE-SDS to support process development decision-making, where high throughput is essential, are made inefficient because of this limitation. A new instrument capable of running eight capillaries in parallel, thus enabling an 8-fold increase in throughput and decrease in turnaround time, has become available. This talk focuses on a thorough evaluation of this instrument. Details and results of experiments performed will be described.
Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own12:10 pm
Refreshment Break in the Exhibit Hall with Poster Viewing12:40 pm
DIGITAL INITIATIVES TO ACCELERATE ANALYTICAL DEVELOPMENT
Standardization of Data Collection and Analysis in Analytical Development
This presentation will focus on the necessary steps to standardize data collection and automation practices in an established analytical development laboratory with 30 analysts running 40 different assays. We will detail our challenges and progress to standardize data storage practices, automate routine assay setup, and make our data searchable to our broader organization. We will discuss the advantages of this approach and present our roadmap for future development.
Expanding Assay Robustness with Computer Vision
Cell cultures expressing biotherapeutic molecules are routinely monitored using cell counters to differentiate healthy and dead cells to measure overall viability. Process development scientists can infer additional cell morphology insights by inspecting cell counter images, but this is a time-intensive process that does not scale. We applied transfer learning and fine-tuning principles to the YOLOv5 algorithm to develop a computer vision model for monitoring cell morphology.
Bioprocess intensification by, for example, higher cell densities and prolonged bioproduction processes aiming at increased yields, while maintaining the end-product quality, are key initiatives in many biopharma process development labs. Here, we show two case studies of improved control of cell culture processes: the first one focuses on the optimization of feeding strategy by daily spent media at-line amino acid analysis, and the second focuses on automated glucose control by near real-time online measurements of glucose and lactate.
- Bring your bioprocess analytics to the point-of-need to enable better understanding and decision-making in your development projects
- Expedite process development with fast, easy-to-use analytics on key nutrients and metabolites
- Remove barriers through characterization of your bioprocess and the nutrient levels required for high yields of safe and efficient product
Refreshment Break in the Exhibit Hall with Poster Viewing3:00 pm
PLENARY KEYNOTE: LEADING TO TOMORROW'S ADVANCES
Current and Future Trends in Biomanufacturing of New Modalities
Using exosomes as an example, this presentation examines the current and future trends in biomanufacturing, and the technologies needed to manufacture emerging modalities at scale. Traditional biomanufacturing methods do not provide the industrialized, commercially scalable, highly efficient and reproducible manufacturing process essential for this new class of biotherapeutics- so we built it from the ground up.
The Digitalization of Biomanufacturing
A fully instrumented testbed is described for the end-to-end integrated and continuous manufacturing of monoclonal antibodies. The testbed consists of parallel bioreactors, simulated moving bed chromatography systems for capture and polishing, bespoke viral inactivation, and a MAST auto-sampling system. Experimental results are compared with a digital twin for continuous runs lasting 30 to 60 days each, which include variations in metabolites and glycosylation profiles in designed experiments. The increased consistency in the glycosylation profile of the monoclonal antibodies being produced is quantified when going from batch to semi-batch to perfusion mode, and when moving from start-up to quasi-steady conditions.
Networking Reception in the Exhibit Hall with Poster Viewing5:00 pm
Close of Day6:00 pm
Registration and Morning Coffee7:30 am
EMERGING METHODS AND TECHNOLOGIES
Leveraging Automation for Increased Throughput of Vg Titer Assays
Manual execution of Vg titer assays (qPCR and dPCR) leads to sample testing bottlenecks, resulting in a long turnaround time for Vg titer results. This talk will present case studies highlighting how Spark Therapeutics is using automation to increase sample testing capacity (4X over manual). It will describe strategies to expand throughput using integrated work cells, which will culminate in faster delivery of life -saving gene therapies to patients.
Applications of Native Mass Spectrometry for Biotherapeutic Characterization
Native MS is a technique enabling the study of intact and non-covalent protein species that has become increasingly popular as a biotherapeutic characterization tool during analytical development. Coupling nanospray MS with native chromatographic separation methods allows us to directly characterize variants without time-consuming offline fractionation. We have used native MS to investigate format-specific variants for multiple biotherapeutics, including co-formulations and novel bispecifics, which will be discussed in this presentation.
Coffee Break in the Exhibit Hall with Poster Viewing9:00 am
Breakout discussions provide an opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges. Please visit the breakout discussions page on the conference website for a complete listing of topics and descriptions.
Affinity Chromatography Mass Spectrometry - A Function-Structure-Based Approach for Streamlined Critical Quality Attribute Assessment of Biotherapeutics
Affinity chromatography with online mass spectrometry hyphenation (AC-MS) on relevant binding partners of therapeutic proteins allows streamlining of the assessment of critical quality attributes. We are establishing an affinity column toolbox, including important receptors and targets, which are of high interest for the biopharmaceutical field. AC-MS as novel technology provides unprecedented resolution and sensitivity of functionally distinct proteoforms and, hence, is expected to overcome current analytical challenges of biopharmaceutical analysis.
USP Standards and Tools to Support Implementation of MAM
MAM for analytical testing of biotherapeutics is gaining traction due to its potential to improve efficiency and provide more detailed information on PQAs as compared to conventional methods. This presentation will focus on the development of USP standards and tools to support MAM for product characterization and quality control. Considerations that impact the quality and consistency of MAM, approaches to enhance the robustness, and case studies will be discussed.
Sponsored Presentation (Opportunity Available)11:30 am
Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own12:00 pm
Refreshment Break in the Exhibit Hall & Last Chance for Poster Viewing12:30 pm
PRODUCT QUALITY AND IN-PROCESS ANALYTICS
Increasing the Throughput of Process Development Analytical Studies
Biologics hold incredible promise in alleviating or curing life-altering illnesses and continue to be one of the fastest growing classes of therapeutics. In both discovery and development, characterization by mass-spectrometry and other analytical assays is often a bottleneck and necessitates high-throughput methods to optimize sample preparation, data analysis and interpretation. We have developed an end-to-end analytical mass-spectrometry pipeline using robotic automation and cloud-based databases that ensure correct processing and analysis of each sample. The system represents a lab-of-the-future concept eliminating the need for manual sample preparation and instrument operation, thereby improving consistency, bandwidth, and accelerating early molecule development.
Bio-Capacitance as an Analytical Tool to Monitor Cell Growth and Metabolic Status
Bio-capacitance has become a standard method to estimate biomass in cell-based bio-manufacturing processes. There is now a good understanding behind the apparent discrepancies between bio-capacitance and conventional trypan blue-based cell counts in the later stage of culture. Furthermore, capacitance measurements can determine the metabolic status of cells from changes in cytoplasmic conductivity that are indicative of the first stages of nutrient deprivation.
Transition of Multi-Attribute Method (MAM) to GMP for Biotherapeutics
The use of MAM for identity and purity testing of biopharmaceuticals offers the ability to complement and replace multiple conventional analytical technologies with a single mass spectrometry (MS) method. We developed and qualified a MAM workflow for therapeutic mAbs and their coformulations with Lys-C digestion. The developed platform MAM workflow and assay performance evaluation paved the way for its GMP qualification and enabled clinical GMP release of mAb products.
Networking Refreshment Break2:40 pm
LC-MS-Based Product Quality of Antibody-Based Therapeutics Direct from Cell Culture Supernatants
Development and production of innovative biotherapeutics demands bioprocesses that consistently yield a high-quality product. However, current methods to determine product quality do not necessarily capture the actual mix of product and related impurities in cell culture supernatant, but rather what can be captured after purification. We developed a highly-sensitive method that can be applied to the detailed characterization of cell culture supernatants from bioreactors without a falsifying pre-purification step.
Development of a Novel and Rapid HPLC-Based Method for a Comparative Assessment of Biosimilar Structural Heterogeneity
Monoclonal antibody (mAb) drug products are the largest product class of US-licensed biosimilars. Glycosylation, a post-translational modification (PTMs), is a well-defined critical quality attribute with significant impact on Fc-receptor binding affinity which in turn impacts the Fc effector mediated antibody-dependent cellular cytotoxicity. Established methods to assess glycan structures and Fc effector activity are costly and time-consuming. Recently, the FcR-IIIA-NPR HPLC affinity column emerged which could provide a rapid mAb glycosylation assessment. The feasibility of the FcR-IIIA-NPR HPLC affinity column as a rapid assay to identify differences in glycosylation PTMs between proposed biosimilars and their reference products is being ascertained.
Identification Testing on Product Release by 1H NMR Spectroscopy
Identification tests in the pharmaceutical industry should demonstrate that the intended components in a product are present at lot release. These tests should “be able to discriminate between compounds of closely related structure” (ICH Q6A), and so limited specificity in methods such as FTIR can make identification challenging. A case study on formulations with common pharmaceutical excipients and surfactants demonstrates how NMR can serve as a powerful identification method.
Close of Summit4:25 pm