Continuous Bioprocessing: PAT for Process Monitoring & Control to enable RPR
Continuous bioprocessing offers potential to enhance productivity and product quality uniformity while simultaneously decreasing facility footprint and associated operational overhead. Advances in technology and increasing commercial pressures are leading to an increased interest in continuous processing across the biopharmaceutical sector. A number of companies are exploring and advancing continuous bioprocessing and this presents a range of opportunity and challenges, including the use of Process Analytical Technology (PAT) for process characterization, process control, and process robustness, in support of a Rapid Product Release (RPR) strategy.
RecordedFeb 7 201757 mins
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Ben Jeyaretnam (Ph. D., MBA), E&L Analytics Lead, Sanofi, Swiftwater
Pharmaceutical industry has been increasingly using single use systems (SUS) for bioprocessing and storage of intermediate and final bulk material in addition to primary packaging. Before a SUS could be used in the manufacturing process, it needs to be qualified for use by a pre-determined process. This presentation will discuss a variety of challenges, both internal and external to the industry that the end use faces during the qualification process. Complexity of SUS, varying quality of vendor data, component change management, changing regulatory expectations, analytical data generation, logistical challenges during E&L study execution, analytical challenges, and the potential impact of unexpected E&L study results will be presented.
The pharmaceutical industry paradigm change is occurring and industry has taken an important leap towards formality of quality improvement using quality tools. Recent industry and regulatory support of ‘risk-based’ concepts and principles are leading to a ‘desired state’ of industry development and production of pharmaceuticals that have a higher level of consistency in meeting purity, safety and efficacy.
Microbiologists’ role as active partners in the pharmaceutical environment is to help transform industry to a routine Quality by Design paradigm. With the help of quality tools and using the concepts and principles of Quality by Design, a better understanding of how and where to implement microbiological control of processes can be developed, and microbiological purity can be built into products for all patient populations.
Yuyi Shen PhD, Principal Scientist, Grifols, John Cyganowski, Director of Manufacturing Sciences and Technologies Downstream
The desire for innovative technology that can eventually cause disruptive improvement remains high in the biotech pharmaceutical industry. The road between pursuing and developing that technology to genuine implementing is not a smooth ride. In this webinar, the presenter identifies key challenges of implementing innovative technologies and the major drive for implementing innovative technologies and process upgrades. The presenter will share some case studies of implementing successful innovation tools and provide comparative economic analysis based on the understanding the true value of innovation driven process design. The webinar also provide the insight of the balance needs for quality, cost and speed.
Vivek Halan Zumutor Biologics Pvt Ltd, Bangalore, India
This Webinar will discuss MMC in purifying biologics which includes monoclonal antibodies (mAbs), Bispecific antibodies (BsAbs), antibody fragments (Scfv,Fab) and other recombinant proåteins. My discussion is intended for audience from biopharmaceutical industry as well as active collaborators from academic institutes.
Dr Sourav Kundu, Senior Director at Teva Pharmaceuticals Global Biologics R&D
· Facility needs and characteristics for clinical manufacturing
· Single-use or stainless steel?
· When to use single-use equipment
· Hybrid manufacturing facilities – best of both worlds
· Teva’s clinical manufacturing facility – attributes, layout, construction, qualification, choice of equipment
· Final thoughts
John Duguid, Senior Director, Research & Development at Vericel Corporation in Cambridge, Genzyme
Rapid detection of contaminants is essential for cell therapy products with short shelf lives. Integrating quality into the process through lot segregation, raw material qualification, environmental control, personnel training, and detailed procedures is critical because final results for conventional microbiological tests may not be available prior to product release or patient administration. EMA approval of the MACI MAA in 2013 followed by US FDA BLA approval in 2016 included three RMM product release assays for sterility, endotoxin, and mycoplasma.
This webinar reviews the constraints and complexities of vaccine product development and manufacture.
The evolution of bioprocess and analytics innovation and technologies to overcome these challenges are discussed.
The strategy and leveraging of innovation and technology for rapid product development and accelerating timelines is described.
Case studies to illustrate the advances in vaccine development and manufacture are illustrated.
A look into the future with state of the art technologies.
Ramila Peiris, Ph.D., Manager, Process Modelling and Process Analytical Technology, Sanofi Pasteur
The utilization of Multivariate Data Analysis (MVDA) techniques at Sanofi Pasteur, Toronto site has demonstrated innovative capabilities for improved process understanding, control and diagnostics. Examples from several successful and high impact applications will be presented. These examples cover the application of MVDA techniques in multivariate process control, root cause investigations and process analytical technology (PAT). The areas of application include fermentation, downstream purification and product formulation stages.
• Understanding extractables and leachables for better adoption of single use systems
• Ensuring safety of drug through determining the level of leachables throughout product life cycle
• Case Study of implementation of standardized testing protocol
Brian O’ Mara, Senior Research Scientist I, Bristol-Myers Squibb and Alexei Voloshin, Global Application Strategy Specialist
Title:Impact of Depth Filtration on Disulfide Bond Reduction during Downstream Process
Presenter: Brian O'mara, Senior Research Scientist I, Bristol-Myers Squibb
• Understand disposable depth filtration technology used in the recovery of antibodies from CHO cell cultures as a unit operation leading to cellular lysis under particular operational conditions • Study how cellular lysis occurring during depth filtration releases endogenous REDOX regulating enzymes and co-factors into the clarified harvest, resulting in the reduction of antibody interchain disulfide bonds • Classify critical process parameters and quality attributes of the clarified harvest to be monitored during filtration development • Discuss risk mitigation strategies to control antibody reduction when using single-use disposable technologies in the recovery of antibodies from CHO cells
Dr Anita Krishnan, Lupinand -Dr. Annu Uppal, Global Demo Lead and Advanced Workflow Specialist at SCIEX
Biotechnological products are so complex, that manufacturing biologics which are both cost-effective and with best product quality, is a technical challenge. In the context of biosimilar manufacturing at each step, the sponsor should evaluate the extent to which there is residual uncertainty about the biosimilarity of the proposed product. Often there is remnant quality difference beyond the capability of process to address. In such instances, in-depth understanding of the process, impurities, analytical methods, the mechanism of action (MOA) of the drug substance and clinical relevance of any observed structural differences, will help in implementing novel CMC strategies. This talk will examine the elements of biopharmaceutical development that lead to successful licensure of biotherapeutics.
Thorsten Lorenz, Team Head Developability Assessment Biologics, Novartis
Title: Developability Assessment of Therapeutic Proteins – A Toolbox for Tackling Increasing Complexity
Presenter: Thorsten Lorenz, Team Head Developability Assessment Biologics, Novartis
Early lead selection of biotherapeutics during preclinical development requires careful characterization of a variety of molecule properties to reduce the risk for encountering unexpected obstacles during technical development. The diversity and increasing complexity of new protein formats requires a change from former platform approaches often applied for antibodies, to project specific strategies. The developability assessment concept applied at Novartis combines information addressing various technical areas, such as expression, aggregation propensity, process fit, stability, physicochemical properties, etc. This integrated concept prior to lead selection provides a thorough, yet resource efficient approach to select suitable candidates.
Marina Kirkitadze , Deputy Director, Head of Biophysics & Conformation Unit, Analytical R&D Biochemist & Kristen Kalbfleisch
The focus of this presentation is the application of Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Fluorimetry (DSF) methods to characterize vaccine components and their stability. Additionally, FTIR can be applied for the identification of final vaccine products, and DSF can be used to distinguish different formulations of vaccine candidates. These methods, when used in conjuction, provide valuable information regarding characterization and stability in the final stages of vaccine manufacturing.
Next generation processes: What model works the best in Asia?
Compare and contrast the available full scale processing technologies, and discover what works the best for manufacturing next generation therapeutic products in Asia.
Biologics are complex and hard to make, which helps to explain why biotech manufacturing plants are huge and expensive to build. To be competitive, manufacturing must be efficient and cost-effective and should brainstorm economical ways to manufacture biologics.
Biosimilars are a cost competitive market. Pricing may have a direct impact on market share, and return on investment. The market for biologics, including approved and in pipeline like ADCs, antibodies & antibody fragments present both tremendous opportunity and challenge. Challenges necessitates looking beyond the current platform philosophy for how to modify the process with a goal to increase overall productivity in a flexible manner.
The current processing paradigm of large manufacturing facilities dedicated to single product production is no longer an effective approach for manufacturing next generation therapeutic products in Asia.
Cost Effective Biosimilars Manufacturing may include
Single-use technologies and continuous upstream processes have proven to be cost-efficient options
Aspects of continuous manufacturing in both upstream and downstream manufacturing are being incorporated thereby increasing yields through a combination of longer production run times, more stable and higher secreting cell lines
Technologies enabling high productivity, right-sized, small footprint, continuous, and automated operations are being evaluated.
Adaptive control techniques are set to minimize development timelines and enhance process robustness
Partnerships will continue to transform biosimilars industry. In order to gain access to developed markets, Indian biosimilar manufacturers are partnering with multiple local established manufacturers and big pharmaceutical companies
Continuous improvement, risk mitigation and adherence to compliance rely on the successful execution of key initiatives aligned with an organization’s strategic imperatives. This article summarizes the Project and Portfolio initiatives at Shire’s Biologics manufacturing facility at Shire, Lexington, MA site. In addition to practical advice, the authors discuss the need for sound business processes, alignment with Finance and budget cycles, and play special attention to the importance of resource allocation and management.
Dr Yifan Wang, regulatory research scientist, FDA CDER and -Dirk Leister, Head of the Application team Thermo Fisher Scienti
In continuous manufacturing of solid dosage forms, continued assurance of process performance and product quality is based on accurate and consistent flow of solid materials. Acknowledging the multidimensionality of material flow properties is often the first step to explore the material knowledge space. In addition, modular operations such as feeding and continuous blending often requires additional material testing for better understanding of process dynamics. As a key element of control strategy, tolerance of incoming material variations needs to be considered. The FDA’s Division of Pharmaceutical Quality Research is working to understand the impact of material properties and explore the material knowledge space for continuous manufacturing of solid dosage forms.
Narasimha Rao Nedunuri, CEO of CLONZ Biotech, and José Castillo, PhD, CTo and co-founder of Univercells
Continuous processing has been widely employed in many biological manufacturing processes. In recent years it gained the momentum in the field of Biosimilar manufacturing due to an ever-increasing pressure for reduction in manufacturing costs.
Potentially, the continuous processing offers Lower Cost of Goods, ease of scalability, and lower manufacturing footprint and hence became a topic of interest to many biosimilar players. Ongoing research on various new technologies for continuous operation, both in upstream and downstream processing may potentially be a game changer. Top on the wish list being, integration of all the multiple unit operations into a single continuous process with real time analytical tools.
Though there are several challenges to develop and adapt continuous bioprocess, the magnitude of potential benefits are currently driving the research programs worldwide. India , being a significant global player in the biosimilar domain, currently making efforts to adapt these novel processes to make the drugs more cost effective.
The need to measure and characterize proteinaceous particles in therapeutic protein products has been emphasized by regulators. USP is a new chapter that addresses the limitations of USP for therapeutic proteins in measurement of subvisible particles. USP is a guidance chapter addressing the task of characterization of particles with the emphasis on proteinaceous particles. Furthermore, regulatory authorities require that sponsors understand the submicron particle size range of the products also. This article will look at latest regulatory developments, key aspects of the measurement of subvisible and submicron particles in biotherapeutics, as well as the utility of low volume methods.
As a result of the increased adoption of single-use technologies (SUTs) in biotech manufacturing, companies need to develop and implement programmatic approaches for the management of these systems under regulatory compliance. This webinar discusses the key aspects of such programs, with emphasis on collaboration with suppliers, cost management, as well as practical insights about the use of SUTs.
The Journal for Asia's Pharmaceutical and Biopharmaceutical Industry
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