BioTech 2010 7-8 June 2010 Abstracts

Author	Title	Year	Company (Country)	Reftype
Büchs, J.	The RoboLector, a sytem for automated microtiter plate cultivations with full on-line measuring capability [Abstract]	2010	RWTH Aachen University (Germany)	standard
Abstract: Although modern methods of molecular biology and systems biology has led to a rational design of mammalian cells, screening of large numbers of clones and media is still one of the most important tasks in biotechnology. For this purpose shaken flasks and increasingly microtiter plates are employed. However, suitable, defined and reproducible experimental conditions are required to obtain meaningful results. Therefore, the culture conditions must be carefully evaluated and characterised. Mixing problems are easily encountered especially in microtiter plates and are not always detected due to absence of on-line monitoring. An insufficient treatment and nutrient supply of the cells can alter metabolism and hence mislead the outcome of the experiment. It is also a very common practice in large screening projects that only the final product titre is measured at the end of the culture for the evaluation of the “best performes”. In the recent years several approaches were introduced to follow microbial cultures in shaken bioreactors like shake flasks or microtiter plates. It became obvious that the cultures can behave in a quite unexpected way and most relevant and essential information is lost, if only the final product titer at the end of the cultures is utilised for evaluation. As a result, the screening may be directed to an unknown and non-intended direction or may even fail. New methods and techniques are introduced to measure the oxygen and carbon dioxide transfer rate and the respiratory quotient in shake flasks and microtiter plates (RAMOS) and the optical density, NADH fluorescence, pH and DOT by optical means in microtiter plates (BioLector). If the desired product can be fused to a fluorescence protein, like GFP or YFP, also the product formation can be monitored on-line. It is of utmost importance that the operating conditions of the applied shaking bioreactors are suitable and shaking motion is not stopped during the measurement. Otherwise e.g. power input, mixing and oxygen supply is interrupted and the micro-organisms will ongoingly rearrange their metabolism to cope with these disturbances of their environmental conditions. Therefore, our on-line monitoring techniques are applicable during continuous shaking of the bioreactors. The RoboLector is the newest device in this family. It is comprised of a combination of the BioLector and a pipetting robot with a Hepa filter (laminar flow bench). This makes completely automated experimentation possible. This will be demonstrated by an inductor profiling. Inductor concentration and induction time is varied in the same experiment. The data of a single experiment will provide detailed information on the optimal induction conditions. Results obtained for CHO and insect cells will be reported.
BibTeX: @standard{Buechs2010, author = {Jochen Büchs}, title = {The RoboLector, a sytem for automated microtiter plate cultivations with full on-line measuring capability}, journal = {RWTH Aachen University (Germany)}, year = {2010} }
Cinkaya, I.	The impact of disposables on the manufacturing of biosimilars [Abstract]	2010	Merckle Biotec GmbH (Germany)	standard
Abstract:The approval of the first recombinant Insulin in 1982 was the starting point for the success story of the biopharmaceutical industry. Followed by other biopharmaceuticals like Somatotropin (rhGH), Erythropoetin (EPO) or Granulocyte colony-stimulating factor (G-CSF) the eighties mark the age of hormone substitution products. After three decades of this innovative time period this class of products have demonstrated their right to exist and are still on the market. However, the health care authorities are facing high treatment expenses, which limits the use of this products to a broader population. Meanwhile the patents expired or going to be expire in the next years. This gives other companies the opportunity to launch biosimilars, from the regulatory point of view products with comparable safety and efficiency to a reference originator product. This new emerging field of biosimilars provide the opportunity to develop manufacturing processes and facility designs considering disposable technologies. Disposables may posses a valuable alternative to classical stainless steel approaches, which was missing some decades before. An overview on the biosimilar business, the manufacturing strategies including monoclonal antibody production and an excerpt of the case-study Merckle Biotec will be given.
BibTeX: @standard{Cinkaya2010, author = {Irfan Cinkaya}, title = {The impact of disposables on the manufacturing of biosimilars}, journal = {Merckle Biotec GmbH (Germany)}, year = {2010} }
Eisenkrätzer, D.	Implementation of new bioreactor & information technology into existing facilities [Abstract]	2010	Roche Diagnostics GmbH (Germany)	standard
Abstract: With the increasing number of new biological entities to be developed, Roches R&D plants face several major challenges: 1. The development must be place cost-efficient. 2. Short development times enable the early start of clinical studies. 3. High flexibility is required regarding the capacity and type of the processes. 4. The transfer from R&D plants into production facilities must run fast and smoothly. The requirements mentioned above lead to the development of a concept for our pilot plants that illustrates an alternative to the highly automated hard piped stainless steel plants we built before. In order to expand our capacities for process development and to implement the new concepts for plant operation, an investment project of 172 million € was approved in January 2008 by Roche’s Cooperate Executive Committee. This concept of the pilot plants is based on a process platform of Single Use Equipment working together with classic steel & glass equipment in different modular plants. To ensure fast and efficient process development, tools to increase equipment utilization will be established. All plants and all equipment are working together in one fully electronic “Data Acquisition and Management and Analysis System”. A major component during the elaboration of the new plant concept has been the evaluation of single use bioreactors (SUB). In a joint evaluation study of the sites in Basle and Penzberg, different SUB models were characterized up to a scale of 500 L and their suitability was examined in numerous fermentations. In order to ensure a compatibility of the single use bioreactors with the used media and cells, these tests were performed using our platform technologies for the development and production of antibodies. These platform processes require the realization of • Short mixing times • High mass transfer rates and • Sufficient power input. In the course of the evaluation, the best suitable SUBs were adapted in co-operation with the vendor to our requirements. Finally we ended up in a Roche-specific bioreactor design that guarantees comparable results to the existing stainless steel bioreactors. Apart from mechanical process engineering the adjustment of the automation systems plays a major role for the acceleration of the development process and increase of the flexibility. The development of an appropriate automation system covers several aspects: • Reliable and précised single use sensors are needed to operate SUBs in an efficient way. • The plant control system must integrate analytical devices, classic and single use bioreactors and harvest equipment using different control cabinets from different vendors. • The plant control and automation system has to integrate the operation of modular plants and research laboratories in different facilities. • Nevertheless, full remote control of all equipment and the use of advanced control algorithms must be feasible. • Interfaces of the data acquisition system have to support the use of many other different software tools used in R&D for process design and analysis. Having a complete electronic documentation & automation system available, we can use the advantages of our platform technologies to accelerate the development process.
BibTeX: @standard{Eisenkraetzer2010, author = {Detlef Eisenkrätzer}, title = {Implementation of new bioreactor & information technology into existing facilities}, journal = {Roche Diagnostics GmbH (Germany)}, year = {2010} }
Giroux, D. & Yunghans*, A.	Novel single-use bioreactors using a pneumatic mixing mechanism: Case studies of large scale evaluation (250 L) and scale-down model (2 L) development [Abstract]	2010	PBS Biotech, Inc., *Amgen Bioprocessing Center (USA)	standard
Abstract: A novel single-use bioreactor system has been developed by utilizing a pneumatic mixing mechanism which converts the buoyancy of inlet gas bubbles to a rotational energy by an air-wheelTM. Since this technology does not require any external mechanical device for liquid agitation, it can offer a simple, compact, and scalable bioreactor system. Cell culture performance in this pneumatic bioreactor system (PBS) was studied and compared to that of other bioreactor systems including the conventional stirred bioreactors and wave-type bioreactors. In addition, scalability of the system was evaluated for biological cell culture performance as well as for liquid mixing performance via computational fluid dynamics (CFD’s). The performance of the small scale unit was characterized as a representative scale-down model that can be used for process development. In this presentation, we will introduce the new features of this novel disposable bioreactor and then discuss the results from biological tests involving CHO cell lines expressing recombinant monoclonal antibodies.
BibTeX: @standard{Giroux2010, author = {Daniel Giroux and Lane Bilbrey*}, title = {Novel single-use bioreactors using a pneumatic mixing mechanism: Case studies of large scale evaluation (250 L) and scale-down model (2 L) development}, journal = {PBS Biotech, Inc., **Amgen Bioprocessing Center (USA)}, year = {2010} }
Hodge, G.	Production of viral, Virus Like Particle (VLP) and soluble subunit vaccines in mammalian and microbial singleuse stirred tank bioreactors [Abstract]	2010	Xcellerex Inc. (USA)	standard
Abstract: Three different types of vaccines have been produced in mammalian single use stirred tank bioreactors: a virus based vaccine produced by Vero cells on microcarriers, soluble West Nile subunit vaccine produced by S2 insect cells and virus like particles (VLP) produced by SF9 insect cells. In addition, three different antigens have been produced in microbial single use bioreactors: recombinant protective antigen subunit vaccine, swine flu hemagglutinin (H1, California strain) and HIV Nef antigen. The paper will present kinetics of cell growth and product formation in mammalian bioreactors and microbial fermenters.
BibTeX: @standard{Hodge2010, author = {Geoff Hodge}, title = {Production of viral, Virus Like Particle (VLP) and soluble subunit vaccines in mammalian and microbial singleuse stirred tank bioreactors}, journal = {Xcellerex Inc. (USA)}, year = {2010} }
Julien, C.	Quality foundation and innovation in single-use systems [Abstract]	2010	Bio Meissner Filtration Products, Inc. (USA)	standard
Abstract: Single-use systems have been adopted by end users as the industry leading value proposition in fluid handling applications, initially for holding buffers and media and progressively for storing and shipping bulk product. The presentation will provide insight into a vendor’s quality foundation borrowing from the principles of quality risk management to establish prequalified dynamic single-use component libraries. Product validation is facilitated through the availability of a vendor’s qualification documentation that includes critical data, e.g., materials of construction and origin, component characterization, sterilization validation, biocontainer integrity, and extractables. Quality-by-design principles in the development of robust welding techniques combined with advanced process control strategies can be implemented to achieve manufacturing capability to address the question of in process biocontainer integrity. Existing PE-based films and a new developed PVDF-based multilayer barrier film along with the applications they each serve in pharmaceutical manufacturing are discussed
BibTeX: @standard{Julien2010, author = {Christian Julien}, title = {Quality foundation and innovation in single-use systems}, journal = {Bio Meissner Filtration Products, Inc. (USA)}, year = {2010}, note = {Bio Meissner Filtration Products, Inc. (USA)} }
Koch, S.	Cultivation of different eucaryotic cell types in single use bioreactors – case studies with different products [Abstract]	2010	Probiogen AG (Germany)	standard
Abstract: The success of a new therapeutic product depends not only on its results in preclinical and clinical trials but to a great extent on the efficiency of process development and the cost-effectiveness of production processes as well as the timeto market. The disposable equipment allows for very short change-over procedures without the necessity of cleaning validation, it supersedes sterilization-in-place procedures and reduces the amount to be invested. The suitability of single-use bioreactors for the production of proteins and other products for therapeutic application is an often-discussed issue between product development companies, contract manufacturers and authorities. The presentation shows how the single-use bioreactor S.U.B. has been used successfully in fermentation processes with different eukaryotic cells for the production of a variety of products on different scales. Data characterizing robustness of the processes, predictability of the yield, product quality and scalability are discussed.
BibTeX: @standard{Koch2010, author = {Susann Koch}, title = {Cultivation of different eucaryotic cell types in single use bioreactors – case studies with different products}, journal = {Probiogen AG (Germany)}, year = {2010} }
Martin, J.	Recommendations for testing extractables and leachables, and the status of the harmonization of testing standards [Abstract]	2010	Bio-Process Systems Alliance and Pall Life Sciences (USA)	standard
Abstract: In 2008, the Bio-Process Systems Alliance (BPSA), the single-use biopharmaceutical manufacturing trade association, published a white paper on supplier recommendations for determination of extractables and leachables from single use systems. The riskbased approach proposed by BPSA was also presented in a seminar for FDA CBER/CDER and has subsequently served as a practical guide for single-use equipment suppliers and drug manufacturers. In the ensuing two years, the joint supplier/user Technology subcommittee of BPSA has developed an expanded guide to testing for extractables for suppliers and users of single use components and systems. Based on end-user feedback, some modifications of the materials and safety risk assessment approach are introduced. Component extractables and process fluid migrants are differentiated from final drug product leachables. Consensus recommendations are provided for common extraction conditions and analytical methods to generate applicable extractables data for a range of process fluids and conditions. Such “generic” extractables data, whether initiated by suppliers or users, can limit the amount of migrant or leachables testing necessary, reduce qualification costs and facilitate more rapid implementation of single-use systems. Rationale is also provided for assessment and comparison of existing component data derived under differing conditions by alternate suppliers.
BibTeX: @standard{Martin, author = {Jerold Martin}, title = {Recommendations for testing extractables and leachables, and the status of the harmonization of testing standards}, journal = {Bio-Process Systems Alliance and Pall Life Sciences (USA)}, year = {2010} }
Vanhamel, S.	How to achieve fast track implementation of single-use technology? Overview of Baseline Best Practices in Film Manufacturing Plus Added Steps for Monitoring and Eliminating Defects. [Abstract]	2010	ATMI Life Sciences (Belgium)	standard
Abstract: In the whole single-use concept the polymer-based film is seen as one of the most crucial components from a risk perspective. Still there is little available on standards or guidelines towards film properties, compositions or manufacturing methods. This presentation wants to shed some light on these topics by giving a more practical insight into polymer selection, film manufacturing and converting this film into Bio Process Vessels. What methods are used, what are the risks and how can we reduce or eliminate them?
BibTeX: @standard{Masy2010, author = {Charlotte Masy}, title = {Manufacture of disposables and quality assurance}, journal = {ATMI Life Sciences (Belgium)}, year = {2010} }
Muranyi, A.	Process intensification with ready-to-use and single-use systems: downstream processing of a monoclonal antibody [Abstract]	2010	GE Healthcare Bio-Sciences AB (Sweden)	standard
Abstract: Increased focus on productivity in biopharmaceutical manufacturing has led to a larger demand for disposable process solutions. ReadyToProcess is a family of products including systems, columns, and membranes for plug- and play alternatives. The product range is developed to achieve operational excellence by enabling LEAN manufacturing. In this presentation, a monoclonal antibody process, from cell culture to final formulation, provides a basis for comparison of a fully ready to use process with a traditional stainless steel process. Process time, contaminant and aggregate removal are studied in detail.
BibTeX: @standard{Muranyi2010, author = {Andreas Muranyi}, title = {Process intensification with ready-to-use and single-use systems: downstream processing of a monoclonal antibody}, journal = {GE Healthcare Bio-Sciences AB (Sweden)}, year = {2010} }
Müller, D.	Disposables from the view of the regulatory authority [Abstract]	2010	Regierungspräsidium Tübingen – Leitstelle Arzneimittelüberwachung Baden-Württemberg (Germany)	standard
Abstract: The presentation of Mr. Mueller states the regulatory view on the use of disposable systems in biopharmaceutical manufacturing. This includes applications of single use systems in active pharmaceutical ingredients production as well as in drug product manufacturing. An introduction followed by an overview of the most important european and international guidelines is given, with emphasis on single use disposables. Regulatory requirements for typical biopharmaceutical applications are discussed and expectations of an european GMP-inspector are given. GMP-aspects of a comparison of single use systems versus multi product equipment are presented, especially with regard to cleaning validation and other quality related documentation. Supplier qualification is one important element of ensuring quality for pharmaceutical products, especially when using plastic disposables in production processes. The requirements for a GMP conform supplier management are shown. Additionally Mr. Mueller presents some of his experience as an GMP inspector in biopharmaceutical industry, giving examples of deficiencies found during official GMP inspections.
BibTeX: @standard{Mueller, author = {Daniel Müller}, title = {Disposables from the view of the regulatory authority}, journal = {Regierungspräsidium Tübingen – Leitstelle Arzneimittelüberwachung Baden-Württemberg (Germany)}, year = {2010} }
Paust, T. & Peuker, T.	Disposables in biomanufacturing: Where we are – a manufacturer’s report [Abstract]	2010	Sartorius Stedim Biotech GmbH (Germany)	standard
Abstract: Patent expiries, competitive pressure, plant utilization, product safety, assurance of supply – just a few of all the buzz words that currently challenge the biopharmaceutical industry. The costs associated with the construction and operation of manufacturing capacities applied to clinical phases and large scale manufacturing require to challenge current manufacturing paradigms. Single-use technologies represent one of the options to look at in order to gain operational excellence. Having past its infant stage single-use technologies are increasingly used in biopharmaceutical manufacturing and are expected to grow substantially in the coming years. The full utilization of those advantages is mainly based on the ability of suppliers to provide the industry with adequate alternatives to existing, multiple-use scenarios. This presentation provides an overview about single-use technologies that are currently used in various up- and downstream manufacturing steps, highlighting a platform and unit operation based engineering approach that helps implement single-use technologies more efficiently. The consequences on modern facility designs will be discussed as well as the impact of cost models to the creation of a basis for decision on technologies to be applied.
BibTeX: @standard{Paust2010, author = {Thomas Paust and Thorsten Peuker}, title = {Disposables in biomanufacturing: Where we are – a manufacturer’s report}, journal = {Sartorius Stedim Biotech GmbH (Germany)}, year = {2010} }
Pralong, A.	Disposables in biomanufacturing: Where we are – a user’s report [Abstract]	2010	Crucell N.V. (Netherlands)	standard
Abstract:Traditional chemical engineering technology based on stainless steel has been applied as a standard in manufacturing of biopharmaceuticals over the last 30 years. Increasing requirements in quality and process control combined with relatively low product titers have led to highly complex and expensive equipment and facility layouts. The construction and commissioning of a new facility can take between 5 to 7 years and cost more than 350 million Euros. Since 15 years, significant efforts have been made to increase process productivity and to develop new manufacturing technologies permitting reduction of CAPEX and OPEX costs. Major developments of disposable technology during the last 10 years have resulted in the possibility to replace traditional stainless steel equipment. The combination of process productivity and new technologies has a significant impact on the strategy for development and manufacturing of biopharmaceuticals and the associated costs.
BibTeX: @standard{Pralong2010, author = {Alain Pralong}, title = {Disposables in biomanufacturing: Where we are – a user’s report}, journal = {Crucell N.V. (Netherlands)}, year = {2010} }
Rachon, A.	Simplifying formulation and filling operations with singleuse technology: a breakthrough in aseptic processing [Abstract]	2010	MILLIPORE S.A.S (France)	standard
Abstract: Well established since a few years for non critical fluid handling applications, single-use technologies are now entering into the complex formulation & filling operations. Based on a vaccine manufacturer case study, the presentation will describe why single-use configuration was considered versus hardware design for a full aseptic processing build. The remarkably fast process integration as well as the critical step of fluid transfer across the sterile barrier (Isolator or Restricted Access Barrier Systems - RABS) via an alpha/beta transfer port will be discussed. After almost one year of process runtime, a first assessment (benefits review) will be drawn regarding its productivity and economical gains.
BibTeX: @standard{Rachon, author = {Alain Rachon}, title = {Simplifying formulation and filling operations with singleuse technology: a breakthrough in aseptic processing}, journal = {MILLIPORE S.A.S (France)}, year = {2010} }
Zambaux, J.P.	A new service for the biotech / pharma industry: Singleuse fill and finish [Abstract]	2010	Disposable-Lab SAS (France)	standard
Abstract: Disposable?lab had launched the first” Plastic “factory for the final filling of sterile drugs in Bordeaux –France to serve the Pharma and Biotech industry The concept is based on new disposable Isolator which allow to weight to fill and to cap and with a modular concept for the clean room. To produce drugs for phase 1 to 4 require a validated processing. This will help you to get from the pharmaceutical authority, an agreement to supply such drug for human use. Clinical Batches is different from the commercial manufacturing. Each product and each active ingredient are new and not well?known. The cleaning and cleaning validation between each batch is long and difficult to do, specially for bio product. Some manufacturing as oncologic product require too dedicated manufacturing tools. Disposable is the solution. To reach that goal there is a lot of points which had to be solved. How to work on a close system? How to introduce pyrogen free vials? How to protect the operator by working under pressure on disposable?...Those points will be developed and presented.
BibTeX: @standard{Zambaux2010, author = {Jean Pascal Zambaux}, title = {A new service for the biotech / pharma industry: Singleuse fill and finish}, journal = {Disposable-Lab SAS (France)}, year = {2010} }
Zarbis-Papastoitsis, G.	Process considerations for clarification and downstream processing of high titer and high cell density PER.C6® harvests using single-use technologies [Abstract]	2010	PERCIVIA, LLC (USA)	standard
Abstract: Advances in single-use technologies enable greater speed, flexibility, and a smaller footprint for biologics manufacturing facilities. In a disposable scheme, traditional chromatography column operations are replaced with adsorptive membranes or other non-traditional purification methods. The purification steps implemented in a fully disposable process should meet the requirements of low cost, easy implementation and operation, and scalability. In this study, a disposable downstream process was developed for the clarification and purification of a monoclonal antibody expressed in PER.C6® suspension cell culture. The cell culture harvest was clarified by enhanced cell settling (ECS™) and optimized depth filtration. The monoclonal antibody was further purified by a combination of single use technologies and finally concentrated by ultrafiltration/diafiltration. The product recovery was 63% and the HCP reduction was 3.7-4.1 LRV for two different scales. The economics of the single use technologies process were compared to a traditional manufacturing process using cost model analysis.
BibTeX: @standard{Zarbis-Papastoitsis2010, author = {Gregory Zarbis-Papastoitsis}, title = {Process considerations for clarification and downstream processing of high titer and high cell density PER.C6® harvests using single-use technologies}, journal = {PERCIVIA, LLC (USA)}, year = {2010} }

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