The Evolution of MAbs from Research Reagents to Mainstream Commercial Therapeutics
Maurizio Zanetti, J. Donald Capra in The Antibodies, 1999
Cloning of Ig genes, amplification of CHO cell lines, and establishment of a “parent seed stock” (PSS) are only the initial steps in the development of a commercially viable therapeutic antibody. Production levels, media components, and growth conditions all need to be optimized before the CHO cell line can be used for production of antibody for clinical trials and eventually commercialization. Process development is a dynamic process that begins once the PSS is established and is constantly modified and refined up until the manufacture of product for phase III clinical trials, when the commercial process and product specifications should be fixed. Initial process development activities focus on the development of a “master cell bank” (MCB) from the PSS. This is a bank of cells established in typically 300 vials that represents the starting material for all future activities, whether clinical trials or commercial production. As such, this bank must conform to certain criteria, meet certain specifications, and pass certain testing protocols.
Management quality and operational excellence
Robert Jones, Fiona Jenkins, Penny Humphris, Karen Middleton in Managing Money, Measurement and Marketing in the Allied Health Professions, 2018
Execution happens at the level of at least three core business processes. The Strategy Deployment process – the formulation and implementation of strategy.The Supply Chain process – the delivery of products and services from suppliers through the ‘sales channel’. Here one might include indirect demand generators, such as GPs who might make a choice to refer patients to one hospital versus another, based on experiences they have had with these hospitals in the past.Product and Process Development – the creation of new offerings and operating capabilities. Performance and improvement across the key business processes, and thus for the entire organisation, are driven by management quality.
Process Development
Harry Yang, Steven J. Novick in Bayesian Analysis with R for Drug Development, 2019
The launch of the FDA initiative “Pharmaceutical cGMPs for the 21st Century” (FDA 2004a) has spurred significant interest and advances in using QbD principles in drug process development. At the heart of the development is the design space, which renders better manufacturing control and regulatory flexibility when an improvement to the process is implemented. Greater use of available data and understanding of the manufacturing process is the key to successful development of design space. Bayesian methods bring about new opportunities for applying QbD principles in design space determination. In addition, process validation is also a very important component of process development. As drug product development and manufacturing has become more complex, the traditional one-time, three-batch validation can hardly provide sufficient assurance that future batches will meet quality standards. The establishment of a robust design space and determination of the right number of batches for process performance quantification argues for the use of statistical methods capable of synthesizing information from disparate sources. In this chapter, we discussed three Bayesian approaches in the identification of CQAs, development of design space, and process validation. Many other aspects of process development can also benefit from the use of Bayesian thinking and principles.
Benchmarking biopharmaceutical process development and manufacturing cost contributions to R&D
Published in mAbs, 2020
Suzanne S. Farid, Max Baron, Christos Stamatis, Wenhao Nie, Jon Coffman
At the beginning of the evaluation, the model builds up the timeline of the development pathway according to the inputs on duration of pre-clinical and clinical trials. Then, based on their material requirements, the model generates manufacturing activities with the appropriate number of production batches. The timings of manufacturing activities are set to meet the clinical material requirement. The process development activities are planned to provide technical support for manufacturing at various stages. After the model plans all the clinical and CMC activities for developing a single product, it calculates how many products the user needs at each step to achieve the target number of market successes, based on the clinical success rates. With the number of products being developed and the cost of developing each one determined, the total cost is evaluated.
Using online content uniformity measurements for rapid automated process development exemplified via an X-ray system
Published in Pharmaceutical Development and Technology, 2019
Bernhard Wagner, Thomas Brinz, Johannes Khinast
Obviously, there are several process parameters (i.e. CPPs), which may affect the CQAs. Likely, there are strong interactions between the CPPs of the different process steps. The CPPs influence each other. As such, rather than testing each single unit on its own, the combination of units should be examined as a whole via the RAPD. One example is given by the feeders that feed continuously into the blender. A fluctuation in the feed rate can induce variations in the final mixture. For some materials, feeding can be a challenging task and significant fluctuations may occur. However, whether these fluctuations are critical for the process cannot be determined without considering the subsequent process steps. For example, the blender may be able to dampen the fluctuations (Weinekötter and Reh 1995; Gao et al. 2011) or fluctuations in the feed may be acceptable, if their influence on the content uniformity is negligible (or below the pharmacopeia limits). This is why in terms of process development it is important to consider the process as a whole. Consequently, the combination of a content check and the RAPD can be a valuable solution for the development of a continuous-capsule filling process.
10th antibody industrial symposium: new developments in antibody and adoptive cell therapies
Published in mAbs, 2023
Ana Antunes, Luis Alvarez-Vallina, Federico Bertoglio, Nicolas Bouquin, Stéphanie Cornen, Francis Duffieux, Pierre Ferré, Raphaëlle Gillet, Christian Jorgensen, Mark B Leick, Bernard Maillère, Hélène Negre, Mireia Pelegrin, Nicolas Poirier, Dietmar Reusch, Bruno Robert, Guy Serre, Alain Vicari, Martin Villalba, Christoph Volpers, Gavin Vuddamalay, Hervé Watier, Thierry Wurch, Lennart Zabeau, Stefan Zielonka, Baolin Zhang, Alain Beck, Pierre Martineau
During her presentation, Dr. Christelle Dagoneau (Head of Global Business Development, Just Evotec Biologics, Toulouse, France) described their unique platform that integrates the discovery, design, engineering, development, and manufacture of biologics in very flexible and easily deployable production facilities called J.POD®. C. Dagoneau showed how the intrinsic molecular properties of antibody sequences can result in lead candidates that are difficult to manufacture or keep stable in formulation. This translates into process development and manufacturing challenges that can substantially affect costs and timelines. Just-Evotec Biologics uses its Abacus™ software, an in-house suite of proprietary computational tools, to predict molecules and conditions for development. She also described how J.POD® accommodates perfusion, intensified fed-batch, semicontinuous, and end-to-end continuous biomanufacturing processes at a standard 500 L scale to deliver from few kilograms of antibodies for “first-in-human” studies to metric tons of drug substance (commercial biomanufacturing) for commercial supply.
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