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Ed Boyden, Ph.D.
Tools for Mapping and Repairing Disease States: Can We Make Therapeutic Invention into a Mature Design Science?
Massachusetts Institute of Technology
J. Craig Venter, Ph.D.
Genomics, Advanced Imaging and the Future of Medicine
Human Longevity, Inc.
Tyler Jacks, Ph.D.
The Convergence Model of Cancer Research: Solving the Problems of Cancer through Interdisciplinary Approaches
Massachusetts Institute of Technology
Cissy Young, Ph.D.
Women’s Leadership Dinner*
Russell Reynolds Associates
Responding to economic pressures to reduce capital investment, cost of development and cost of goods, new platforms are emerging built on the principle of flexibility, and making heavy use of single use products, continuous manufacturing and alternative technologies. XCell™ ATF, OPUS® Pre-packed Columns and TangenX™ SIUS™ technologies drive productivity gains and COG improvements into upstream and downstream bioprocessing. In this talk, we will look at the individual benefits of these technologies to specific unit operations and then the combined benefits to a complete process.
Viral Safety: Regulatory Strategies, Considerations and the Challenges of Defining and Defending Validation Testing Packages for Viral Clearance
Analytical & Quality: Analytics for Product and Process Characterization
Process development and characterization at Lonza Biologics is being increasingly automated to make most efficient use of time and available material whilst investigating multiple parameters in a DoE approach. This presentation describes Lonza’s latest advances in high-throughput analytics. This includes the support of upstream with HT small-scale purification, product quality testing and automated N-linked glycan screening and downstream with our latest platform for automated impurity (HCP, DNA, PrA) quantitation.
We developed and maintain an R-based model development platform, which can be used to generate the best models for the prediction of CQAs with process variables and the prediction of any continuous responses with high-dimensional predictor variables, i.e. the cases where sample size is less than number of predictor variables.
Glycan profiling is a widely used analytical tool in support of cell line screening and upstream process development. High-throughput methods for glycan analysis are necessary for testing large numbers of samples with short turnaround times for the results. We have explored several glycan analysis methods on a variety of platforms and will present a comparison of methods for high-throughput glycan analytics (e.g. UPLC and LabChip).
Manufacturing Strategy: Strategies for Optimizing Manufacturing Efficiencies and Process Controls
Developers of biologics must get to commercial manufacturing as fast as possible and at low cost without compromising on flexibility or quality. Sartorius Integrated solutions team have gathered extensive experience of implementing single-use and hybrid process trains into both clinical and now commercial operations with over 200 projects implemented to date. Through end-user case studies Boehringer Ingelheim and Synthon Biologics, we will provide insight into how such platforms enable maximum operating flexibility and a very short timeline to market. We will explain how an automation strategy working with electronic batch records can reduce operator errors working with single-use and enable process monitoring, control and optimization ensuring highest quality of your product.
Biogen is taking a holistic approach to develop and implement enhanced process controls for Mab manufacturing in its manufacturing network, including the Next-Gen manufacturing facility, currently under construction in Solothurn, Switzerland. The intended goals of enhanced process controls are to improve manufacturing process robustness, consistency and operation efficiency. This presentation will describe the integration of prospective raw material control, feedback and feed forward controls using process analytical technologies, “right time” release testing and predictive models to achieve the desired enhanced controls, as well as considerations on process validation and learning from full scale manufacturing implementation.
Drug Product, Fill-Finish & Formulations: Innovations in Freeze, Storage and Thaw
Develop a robust bulk freezing process is critical to significantly extend drug substance shelf-life, usually from months to years, and to ensure a smooth drug product manufacturing operation. Several techniques for large-scale bulk freezing are available, but each has its own limitations. These leading techniques will be compared, and cryoconcentration and other common problems associated with bulk freezing will be discussed. A case study of developing a controlled freeze thaw process and its impact on the frozen bulk stability will be presented.
Bulk volumes are increasing rapidly and the existing Single Use Technologies do have their limitations in the field of Freeze/Thaw/Transportation of it. We show a way how to push this process to the next level. A scalable end-to-end concept with reduced manual manipulation and full traceability draws the line to reduce product loss and an increase in patient safety.
Cell Culture & Upstream Processing / Recovery & Purification Shared Session: Innovation at the Interface of Upstream/Downstream Processing
High aggregate levels (20-30%) are commonly observed during bivalent bispecific antibody (BisAb) process development and often exceed the capabilities of the monoclonal antibody (mAb) purification platform process in removing the impurity to acceptable levels. Calcium phosphate precipitation has recently been demonstrated to be an effective method for removing approximately ~10-20%of the aggregates present. One disadvantage is the high turbidity (1,000-3,000 NTU) generated as a result of precipitate formation. Although depth filtration has been used to remove these precipitates, the large filter areas required are not practical for large scale production. Acoustic wave separation (AWS) devices have been marketed as a companion technology to cell culture harvest as an alternative to centrifugation. In this study, a novel application for the use of the AWS system (Pall Cadence Acoustic Separator) is described, and improvements to depth filtration capacity in the purification process are showcased. Varying concentrations of calcium phosphate were used to identify the optimal operating conditions. Studies were performed with clarified cell culture fluid and with neutralized low pH viral inactivated product. Turbidity reduction of greater than 90% was achievable for most product pools. Depth filtration capacity evaluation of the AWS-treated feed streams showed > 2x improvement in filter capacity compared to feed streams under similar conditions. Interestingly, at lower calcium phosphate additions to feed streams, AWS treatment was able to reduce turbidity from 1100 NTU to 50 NTU, allowing for direct sterile filtration without the need for depth filtration. The ability of this technology to significantly reduce turbidity improves the scalability of calcium phosphate precipitation processes and has great promise for its use in removing aggregates present in bispecific antibody purification processes.
Biogen has two 15K facilities in Research Triangle Park, North Carolina and Hillerod, Denmark, and utilizes both for our manufacturing partnerships with other companies. Within this manufacturing relationship, we have also formed a strong and collaborative technical foundation. Projects have now been completed which go beyond Biogen’s tech transfer and manufacturing capabilities by leveraging our platform CHO process media within the partnership to deliver improved protein production. Within our partnered manufacturing molecules, several molecules have high material demand and relatively low titer output requiring high volume and frequent manufacturing; this low output might also require partners to engage more than one CMO and complicate the technology transfer and supply chain. Biogen has thus invested process development resources in upstream, downstream and analytical development, all working together to develop high titer processes in numerous programs. Across multiple CHO cell lines used by partners, the Biogen platform has shown the ability to successfully triple the titer and maintain comparable product quality. The current collaboration not only leverages the strength of the manufacturing partnership, but also facilitates an exchange of expertise from technical teams. This broad technical engagement facilitates technology transfer, enhances manufacturing support, and opens more capacity in the manufacturing facility for the other programs in need with high titer options.
Recent advances in mammalian cell culture processes have resulted in product titers as high as 25 g/L, but have also resulted in significant increases in cell density and cellular debris compared to typical low titer cell culture processes. Also, there is a growing interest to incorporate single-use technologies in bioprocessing to minimize validation, cleaning, and capital investment costs and to increase facility flexibility. Therefore, improvements in harvest processes are essential to overcome challenges associated with conventional recovery methods such as centrifugation or microfiltration.
In this study, acoustic wave separation technology (AWS) was evaluated as a novel method for harvesting monoclonoal antibodies. AWS clarifies cell culture in a continuous manner utilizing the technology of 3D standing acoustic waves (Pall and FloDesign Sonics). Cells and cell debris are trapped by the acoustic forces and agglomerate to form large cell particles that settle out of solution. Several parameters including frequency, packed cell mass, cell density, and feed flow rate were evaluated to optimize process performance. Data demonstrated that the AWS harvest process had minimal impact on product quality. Cell removal% was directly impacted by cell culture density, with process performance significantly improved by lowering frequency and feed flow rate. These studies provide important insights into a novel harvest technology that can be integrated into a manufacturing facility as a single-use, continuous harvest technique with potential to overcome clarification challenges associated with high density cell cultures.
Exhibit Hall Theater Presentations
The C1 platform technology is a hyper-productive fungal expression system which has been used to produce enzymes and proteins at yields up to 100 g/l, with 80% purity (~ 80 g/l of the target protein). C1 is a leap in technology that has the potential to change the way in which both animal health and human biotech and pharmaceutical companies bring their biologic vaccines and drugs to market faster, in greater volumes, at lower cost, and with newer beneficial properties.
FlexAct® BT is a Bag Tester solution for end users to control the absence of leaks that could occur during transportation and handling of 2D bags at the point of use. FlexAct® BT features the Sartocheck® 4 plus Bag tester and a set of two holders to perform pressure decay testing in a safe, fast, easy and reliable way. FlexAct® BT is supplied with a complete validation package and on-site service to achieve an easy validation.
Increasing Phase I/II development productivity to reach the clinic faster is driving the adoption of high throughput analytical tools to reduce the turnaround time for results, increase sample capacity, and provide richer insight into quality. The Octet HTX system, used to assess product titer and detect CHO-HCP and Residual Protein A impurities, is an example HT analytics transforming the development workflow.
In June 2017, BioProcess International published The State of the Industry, a special report and ebook series designed to provide the biopharmaceutical industry with a unique perspective into the business decisions, technological advancements, and scientific breakthroughs over the last 15-years that define who we are as an industry today. This special series examines the successes, failures, and trends that have delivered the industry to this particular point in time. Reflecting the eleven core job functions and demographics that represent BioProcess International’s readership, the State of the Industry provides expert insight into the factors and decisions that impacted each step of the bioprocess. As part of the BWB festival, BioProcess International presents trends in four of the eleven core bioprocess stages: Research & Development; Lab Management; Process Development; Production/Manufacturing
The R&D Perspective: Mapping New Pathways from Discovery to Development
Cheryl Scott, Senior Technical Editor, BioProcess International
The Lab Manager’s Perspective: Ensuring Efficiency, Data Integrity, and Compliance
Maribel Rios, Managing Editor, BioProcess International
The Process Development Perspective: Implementing Tools for Optimization
Maribel Rios, Managing Editor, BioProcess International
The Manufacturing Perspective: Current Approaches to Bioprocess Intensification
Anne Montgomery, Editor in Chief, BioProcess International
The Sony FX500 cell sorter features single use fluidics that can be exchanged between samples to streamline operation and control sample carryover. Here we highlight a case study of sorting memory and naïve T cells in a GMP facility using FX500. System setup, performance and application data supporting this approach will be presented.
What other features should be taken into consideration when evaluating genderless connectors? While genderless interchangeability is a significant advantage, it is not the only feature to consider. You need to ensure that the connector will have the overall functionality to ensure a reliable, repeatable and secure connection. This presentation will review the important connector attributes to consider when selecting a sterile coupling.
Fujifilm's Saturn Platform offers de-risked, rapid and reliable development and cGMP manufacturing for mAbs. The platform encompasses process assessment, analytical development and manufacturing using dedicated facilities with standardized equipment, raw materials, and consumables to which increases efficiency and reduces cost, lead times, and risk. Saturn programs can start with Fujifilm's Apollo CHO cell line or with client cell lines.
This talk will showcase the latest version of Inline Buffer Dilution technology from Asahi Kasei Bioprocess America. The five-pump IBD System can be used to dilute and condition even the most complex aqueous buffers, helping you leverage stock concentrates to save time, save space and save money in your downstream processing plant.
This topic will present the outcome of the joint discussions between BPOG (BioPhorum Operations Group) and BPSA (BioProcess Systems Alliance) for a period of 18 months between 20 drug manufacturers and 12 suppliers regarding the management of supplier change notifications. The team’s journey, from initial scoping and objective setting to the creation of tools and supporting documentation will be presented. The benefits of the team’s change notification structure will be highlighted as a means of encouraging industry adoption of this practice and standardization of the handling of supplier changes.
This topic will present the ongoing activities of the joint initiative between BPOG (BioPhorum Operations Group) and BPSA (BioProcess Systems Alliance) regarding Single Use User Requirements. Currently, 14 drug manufacturers and 16 suppliers are collectively working on this collaboration. The team’s journey, from initial scoping and objective setting to delivering the roadmap and overcoming cross industry challenges will be presented. The benefits of the team’s work will be discussed as a means of encouraging industry adoption of this practice which should encourage swifter deployment of single-use technology due to the implementation of an industry wide standard set of expectations. This will help to mitigate concerns and risks as new biopharmaceutical products are brought to market.
The biopharmaceutical industry produces non-sterile and/or low-bioburden intermediates and bulk biologics (i.e. Drug Substances) using bioburden controlled processes in accordance to Q7A and Annex 2. In many cases, single mold isolation events have received a high level of scrutiny; the goal of this paper is to challenge this paradigm and provide the rationale for an enhanced control approach that focuses on trending of mold species as microbial indicators rather than on single isolation events. Molds, can also be part (in much lower numbers) of the normal microbial population of a biologics manufacturing facility and, therefore, mold isolation is not an unexpected event in non-aseptic processing environments. This presentation provides recommendations from a biopharmaceutical industry perspective on mold monitoring in biologics drug substance facilities and processes. Additionally, recommendations on subjects commonly encountered in the establishment of a monitoring program, such as mold trending, responding to mold isolation events and best practices on mold prevention, are included. These recommendations assist biologic manufacturers in refining their current mold control strategy, as well as developing control strategies for new processes, facilities and products. Establishing appropriate mold control programs is a key element of overall microbial control plans in biologics manufacturing facilities.
Adaptation of potency assays to robotic systems has been a significant challenge for cell-based bioassays. We have experience automating quantitative and potency assays on Hamilton robotic systems, including assays based on proteins, nucleic acids, and cells. We will present the challenges and successes of adapting assays to automation, and share some of the lessons we’ve learned along the way.
Single-use systems which can function as closed systems facilitate streamlined aseptic filling operations. These include isolator based filling systems for final container closure of drug product, but also RABs based filling of upstream process fluids and many operations in between. Best practices associated with designing single-use systems for use in these critical applications will be covered.
Viral Safety: What's New in Viral Detection & Clearance? Learn About Emerging Technologies like NGS, Nanofiltration, MS and More
Manufacturing Strategy: Case Studies of Optimizing and Accelerating Biomanufacturing
In today’s competitive landscape, it is necessary for companies to push for shorter development timelines. Here, a case study will be presented of accelerated cell line development, process development and tech transfer of a CHO process to express an IgG4 therapeutic mAb. The molecule, which was in a Ph1 clinical trial with a moderate-expressing cell line and a 4-column downstream process, was in-licensed for clinical evaluation in other indications. An improved process was developed to manufacture material for use in Ph1b and subsequent trials. After cell line, upstream, downstream, and formulation development, the new process was transferred to clinical manufacturing and the clinical campaign initiated within ~12 months from licensing, or 11 months from DNA to vial thaw. The developed process had >4-fold higher expression than the FIH process, 3 column steps, and comparable protein quality attributes to the material previously used in the clinic. The acceleration strategies taken, technical and timeline issues encountered, and suggested improvements to approach will be discussed.
USG Departments and Agencies are collaborating to align existing strategies, and develop new initiatives to better coordinate R&D activities in the advanced manufacturing space. Approaches to leverage and/or pool resources to incentivize the public and private sectors will be explored. Strategies to bridge basic science research to translational applications and funding opportunities will be discussed.
Analytical & Quality: Biosimilar Product Characterization
Biosimilar development is based on demonstrating analytical similarity to the reference product, with abbreviated clinical studies utilized to remove residual uncertainty. Pfenex Inc., a leader in biosimilar development, has significant experience in deploying our extensive analytical capabilities in support of product development and regulatory reviews. Significant challenges can arise in the process of demonstrating analytical similarity. For example, reference products may contain protein excipients, such as Human Serum Albumin (HSA), that are present in excess amounts relative to the active protein drug, thereby interfering with analytical similarity assessment. To enable a thorough comparison of Pfenex’s interferon beta-1b biosimilar candidate and the marketed HSA-formulated reference product, we developed an HSA-depletion method. By minimizing interferences from the excipient, we successfully conducted additional characterization at all levels of protein structure, including hydrogen/deuterium exchange (H/DX) to elucidate higher order structural (HOS) forms. Additionally, exploration and characterization of possible protein complexes, protein form distribution, and activity for both formulations was performed by 2-dimensional analysis across the product profile. The data from these experiments demonstrate high similarity between Pfenex’s biosimilar candidate and the reference product, based on the analytical methods developed and employed.
Biosimilars promise significant cost savings for patients, but the unavoidable differences between innovator and copycat biologics raise questions regarding product interchangeability. In this study, Remicade and Remsima were examined by native mass spectrometry, ion mobility, and quantitative peptide mapping. The levels of oxidation, deamidation, and mutation of individual amino acids were remarkably similar. We found different levels of C-terminal truncation, soluble protein aggregates, and glycation that all likely have a limited clinical impact. Importantly, we identified more than 25 glycoforms for each product and observed glycoform population differences, with afucosylated glycans accounting for19.7% of Remicade and 13.2% of Remsima glycoforms, which translated into a 2-fold reduction in the level of FcγIIIa receptor binding for Remsima. The same analytical workflows have been applied to characterize other biosimilar mAbs and their reference products. Our mass spectrometry-based analysis provides rapid and robust analytical information vital for biosimilar development. We have demonstrated the utility of our multiple-attribute monitoring workflow using the model mAbs Remicade and Remsima and have provided a template for analysis of future mAb biosimilars.
Drug Product, Fill-Finish & Formulations: Innovations in Freeze, Storage and Thaw
In order to ensure patient safety, some parenteral therapeutics, such as those intended for intrathecal administration, require the final drug product to meet extremely low endotoxin specifications. This talk will present an end-to-end risk assessment approach to design an appropriate manufacturing process control strategy around key endotoxin contributors. The implementation of improved endotoxin controls into next-generation processes will also be presented.
This presentation will discuss trends in aseptic filling including the challenges of implementing single use filling systems. It will also discuss trends in aseptic filling with respect to stainless steel versus single use, including the upstream processes challenges and how single use technology addresses these challenges. The presentation may be a co-presentation with a customer for a case study approach.
Cell Culture & Upstream Processing / Recovery & Purification Shared Session: Early/Late Stage Process Simplification & Acceleration
To enable the accelerated launch of new biopharmaceutical products, process control strategy development efforts need to be efficient yet robust. A new work-flow was developed employing risk assessments and multivariate experimental designs for defining operating ranges and parameter criticality. Using this approach, the timeline for upstream process characterization was reduced by up to 40% for a recent program. Key learnings from this case study will be presented.
This presentation will provide a high level overview of establishing product control strategies using risk-based methodologies. Product control strategies serve as lifecycle management tools that can help instruct, summarize, and consolidate the various manufacturing controls and testing elements used to assess and ensure a robust process for manufacturing safe and efficacious biologics. This presentation provides a step-by-step walkthrough of the various quality risk management activities used to evaluate each attribute's criticality (i.e., potential impact on safety and efficacy) and process capability (i.e., potential impact on process consistency). Considering both criticality and process capability, this presentation will demonstrate how each critical quality attribute can be assigned an overall control risk score, from which the testing strategy (i.e., frequency of testing and/or testing at a particular step in the process) is properly developed. Examples of critical quality attributes primarily formed during the cell culture process will be described and linked to the downstream process by the control strategy. Lastly, a case study will be presented to demonstrate the utility of control strategies for assessing the impact of cell culture process changes and for constructing a new working cell bank qualification protocol.
In order to optimize the bioprocess for recombinant protein production by CHO clone; a design of experiment (DOE) study had been performed using the 0.25L Dasbox bioreactor. During the DOE study several bioprocess parameters were evaluated such as percent of DO, temperature, feeding schedule and feed volumes for the CHO clone. From the DOE study it was found that changing the temperature, feeding schedule and percent of DO; all these factors influenced cell viability, yield of the recombinant protein and the metabolic by product formation. As part of quality by design (Qbd); purification steps were incorporated before scale-up into large scale bioreactor to check the possibility of free light chain and truncation of thiol group
Proper therapeutic antibody glycosylation is critical for its function and can be significantly influenced by it production process parameters, including culture media. Results from two case studies demonstrate the exact nature of glycosylation-function relationship may be antibody-dependent and the potential necessity of antibody-specific approach in controlling glycosylation during its bio-production.
Technological advancements for high throughput process development are allowing scientists to accelerate the time from discovery to manufacturing. In this session we will discuss the importance of using technology to optimize your data management processes to achieve quality at speed throughout the development life cycle.
Roivant Sciences Inc. is currently finishing preclinical studies in recombinant human acid ceramidase (rhAC)—an enzyme replacement therapy for patients with Farber disease. This presentation will demonstrate the collaboration with GE’s Fast Trak services team, where expertise, transparency, and tech transfer were put into best practice. We will share development data and decision-making points during four stages of the project; clone selection, process development, scale-up, and cGMP production.
Generate actionable glycan data from >300 samples per day in your own lab. Introducing a new SCIEX technology. One-hour sample prep of a 96-well plate, compatible with automation. Simply put the plate and the cartridge in the instrument; no other reagents to add. Obtain high resolution actionable data using the reliable chemistry from the makers of the PA 800 Plus.
Once antibody-producing cell lines have been identified, optimizing the culture media can yield higher titers. We automated a factorial design of experiment approach to identify optimal culture conditions. The automation prepared combinations of media components, plated cells in replicate conditions, generated sample and reagent plates for IgG titer analysis, and initiated imaging and XTT assays to measure cell growth.
3M and Biotech Week Boston are sponsoring the Women in BioProcess Roundtable event, where we’ll be connecting women in bioprocessing for a special leadership discussion and luncheon exploring diversity and career development in the industry.
Participants will network with pioneers in the field, learn more about bioprocess career trajectories, and create personal connections with women scientists and executives across a variety of companies. Deeper discussion and mentorship opportunities are included in the event.
• Network with pioneers in the bioprocess field
• Learn from women leaders across a cross-section of companies
• Create personal connections with other women scientists
• Be considered for participation in an ongoing women in bioprocess mentorship program
3M is offering this opportunity to current and future women leaders in science
Sanchayita Ghose, Ph.D., Director, Downstream Process Development, Biologics Process Development, Bristol-Myers Squibb
Register for this Roundtable Luncheon (you may also register for this luncheon during your online registration for BPI)
*All registrations are subject to 3M approval
Viral Safety: Commercializing Production of Biotherapeutics With Respect to Pathogen Safety
Analytical & Quality: Analytics and Characterization Strategies for Complex Products, Viral Vectors and Vaccines
The standard method for evaluating infectivity titration of live virus vaccines is the plaque potency assay. This method is time and labor intensive, and requires manual plating, infecting, staining, and counting of plaques. This assay takes approximately 7 to 14 days to complete. The development of a viral potency assay that can be run in a 96-well plate in a high-throughput format would have the potential for accelerating live virus vaccine programs. Such an assay was developed using a novel stable reporter cell line. This line contains a constitutive promoter that drives a reporter gene encoding an enzyme. Following infection of this line with a live virus vaccine, the reporter enzyme was observed to accumulate in the culture media. A standard set consisting of this live virus vaccine with increasing titers was evaluated in the cell line and plaque potency assays, and concordance between the two methods was demonstrated. Additionally, evaluation of viral stability samples in the reporter cell line showed the same rank-order as the plaque potency assay. Based on these observations, a cell-based assay in a 96-well plate was developed. The overall variability was 29%, which is similar to the plaque potency assay (range approximately 30% to 50%). Because the reporter cell line assay can be run in a high-throughput manner, the variability has the potential to be reduced below 29%. Overall, screening formulations or different process conditions using this method has the potential to accelerate live virus vaccine programs as compared to the traditional plaque potency assay.
Manufacturing Strategy: Change Control Strategies for Materials and Processes in Biomanufacturing
The rising demand of therapeutic monoclonal antibodies and recombinant protein products has necessitated an increase in cell culture production yield and robustness to satisfy commercial and clinical demands. Significant progress has made over the last decade to improve cell culture processes productivity via cell line engineering, culture media optimization, feed strategy improvements, and parametric operational optimization. In recent years, lot-to-lot raw material variation understanding and control has received significant industrial attention to further improve the robustness of cell culture processes. Poloxamer 188 is a common biopharmaceutical raw material that is used as a shear protectant within cell culture media. Historic lot-to-lot variation of a high molecular weight Poloxamer impurity has had significant impact on the robustness of cell culture processes. This talk will discuss the evolution of Poloxamer impurity characterization and control.
The presentation provides an overview of the challenges associated with the increasing adoption of single-use systems (SUS) in bio-manufacturing and outlines a supply chain and quality strategy where raw material specifications and process controls achieve more consistent compatibility with biologics.
High-throughput bioreactor robotic systems have started to replace traditional, labor and time intensive methods of using shake flasks and stirred tank reactors for conducting cell culture experiments but samples from them still need to be assayed off line for measuring cell and product attributes. In this work, we successfully coupled the automated multi-reactor system with an on-line biochemical analyzer which simultaneously addresses the need for a high screening platform and measuring parameters such as cell density, viability, dissolved gases, and metabolite concentrations. A case-study investigated cell density and viability maximization using 12 batch and fed-batch CHO cell cultures (<20 mL) where each culture had its own unique automated glucose feeding strategy based on glucose measurements. Different feeding strategies, such as maintaining different glucose concentrations with a feedback control or predicting and reacting to glucose and viable cell density conditions based on a feedforward control, were carried out depending on the glucose and viable cell density data received by the biochemical analyzer. An optimal cell density of 33 million cells/mL and cell viability of 98% was reached for a fed-batch culture, with an initial cell density of 0.3 million cells/mL and feed strategy maintaining glucose levels at 5 g/L. The case-study demonstrates the capability of the integrated automated and analytic platform to optimize the culture data obtained through online methods and to enhance process development capabilities. The increased productivity of the integrated platform allows for decreased capital cost per experiment and significantly decreased time needed for parameter optimization and should facilitate large multifactorial real time experimental designs, which improve the selection of appropriate scale down and scale up parameters for optimal protein production.
Drug Product, Fill-Finish & Formulations: The Impact of Particles and Light Exposure in Drug Product Manufacturing
While biomolecules are routinely exposed to ICH Q1B exposure levels as part of forced degradation studies, the primary goal of these studies is to gain an understanding on the degradation profile and demonstrate that appropriate analytical methods have been developed to elucidate the various degradation pathways. Since, most of the biomolecules contain light-sensitive amino acids in their chemical structures, exposing them to ICH Q1B conditions may lead to significant degradation (i.e. aggregates). Presented in this talk is a practical approach for assessing the impact of both the visible and ultraviolet light radiations on biomolecules and eventually developing a science-based control strategy for light exposure during the drug product manufacturing process.
Concerns around adequate monitoring of proteinaceous particulates in drug products have increased in the recent years due to potential immunogenicity risk. Recent analytical advancements have enabled robust characterization of particles over a broader size range, well beyond the typical specifications for visible and sub-visible particles. In this presentation, a case study illustrating the propensity of proteins to form nano- and sub-visible particles during dose preparation, handling and administration steps will be discussed for various protein modalities.
Cell Culture & Upstream Processing / Recovery & Purification Shared Session: Case Studies and Lessons Learned
Fully-automated production run using InSCyT generates hundreds to thousands of doses of the target biologic drug over five days with product quality and activity comparable to WHO standards or the product specifications of reference innovator drugs.
To emphasize manufacturing speed and flexibility, we chose to use the microbial host Pichia pastoris for recombinant expression. Pichia rapidly accumulates biomass, can secrete high titers of many heterologous proteins, and is used to manufacture biologic drugs worldwide. Targeted integration of transgenes in Pichia is routine and produces stable cell lines that behave consistently in fermentation. Cell cultivation fluids from Pichia fermentation contain few host-cell proteins enabling simple downstream processing to purify target proteins. This predictable host has allowed rapid process development for both fermentation and purification resulting in a “plug-and-play” approach to manufacturing with InSCyT to date.
How can we continue to maintain a common platform configuration as we aim to expand our product formulary and make more challenging biologics? We have sought to exploit the genetic simplicity of this host to develop a deep and systematic understanding of its performance to guide strain engineering and process development. Our recent campaign to comprehensively characterize the genome and transcriptome has led to discovery of novel promoters, loci, and signal sequences to promote “smart” biologic drug expression in this yeast. Comparative transcriptomic profiling of strains expressing a variety of biologics shows how secretion performance differs depending on protein complexity. This level of host knowledge, combined with the streamlined manufacturing approach designed into the InSCyT platform, can support rapid cycles of drug development and ultimately enable production of a customized formulary focused on patient needs globally.
Chromatan’s CCTC is a new column-free continuous purification platform for mAbs, vaccines and other biologics, providing a new alternative to batch and multi-column chromatography. Multi-million dollar awards from several government agencies have enabled new and exciting research into Integrated End-To-End Continuous Bioprocessing with the CCTC platform. In this talk we will lay out a new vision for the development of a closed and single-use continuous bio-process as well as share new data from multiple evaluations of CCTC for various chromatographic modalities. The data shows high-resolution steady-state antibody purification at < 15 psi operating pressure, high yield, and 5-10X increases in resin productivity vs. batch columns. The operation also shows equivalent or better product quality for contaminant removal and aggregate clearance.
In addition, we will present a new chromatographic resin that was jointly developed by Chromatan and Purolite to exploit the unique capabilities of CCTC’s column-free geometry and low pressure operation. The data shows 70-80% improvement in binding capacity and a 2X improvement in kinetics with this new material which enabled the CCTC system to reach productivities of well over 100 g of mAb/ Liter of resin / hr.
Biotech Week Boston Keynote Presentations
MIT’s Koch Institute for Integrative Cancer Research was created to take advantage of the strengths at MIT in cancer science and cancer-oriented engineering. The Institute fosters interdisciplinary thinking and collaboration to tackle the most challenging problems in cancer biology, diagnosis, early detection, and treatment. Tyler Jacks serves as the Director of the Koch Institute and also runs a cancer genetics and cancer immunology laboratory there. He will illustrate examples of progress against cancer through his own work as well as from collaborative efforts with other scientists and engineers.
This panel on increasing gender diversity in the biopharma industry will focus on actionable strategies and programs that both men and women can work on together to help improve gender diversity in their companies. The emphasis will be on what everyone in our industry can do, whether at small, medium or large organizations, and at every level of their company to make a difference and deliver the benefits of gender diversity for corporate performance.
Actionable takeaways will include how to build programs for:
—Male Allies and Champions for Gender Diversity
—Flexible Work Policies
—Mentorship and Sponsorship Programs
Increasing gender diversity will be critical for continuing to build our innovative biopharma industry in the Boston area and to continuing to deliver economic growth to Massachusetts, so come hear what you can do to contribute in your own organization today.
Sponsored by 3M
Connect with individuals in senior leadership positions and meet the rising stars in the life science industry at the first annual Women’s Leadership Dinner. Adele Gulfo, successful scientist turned business executive, will open the evening encouraging women to “stand on the edge” as leaders. Following Adele’s remarks, attendees will have the opportunity to engage in dynamic networking.
* Requires Festival PassPLUS or Separate Dinner Registration