bio-t bioreactor systems

Transcription

1 bio-t bioreactor systems Bio- and Processtechnology Evolution of Technology

2 bio-t bioreactors Pure Performance In our role as plant constructor with many references in terms of customised design, we are aware of the importance of the role played by functional sterile design, and assign this aspect a central position in the ongoing process of developing our bioreactor systems. The demands placed on the individual components of which any such system is composed are therefore correspondingly high: Top-class manufacturing quality Standardised system components Industrial components available globally Intelligent detailed solutions for optimal sterile design Control concepts from the industrial pharmaceutical plant construction sector bio-m magnetic agitators for installation at the bottom of a vessel or on top are of a particularly sophisticated sterile design, providing process-optimised agitator heads and a long maintenance-free service life. bio-t mini the attractively priced way into the world of zeta systems. Easy to operate and flexible in use, it is ideal for development work in industry and universities.

3 Our biotechnical plant construction range is rounded off by three modular systems, thus filling the gap between the cell bank and the validated production plant: bio-t mini laboratory reactors bio-t pro sterilisable pilot and production bioreactors bio-t xpac multi-bioreactor systems The extensive know how of our bio-technologists, process technicians and software engineers is drawn together within projects thus providing a guarantee for the highest level of process optimisation, be this for laboratory systems or validated process plants. bio-t pro laboratory and pilot bioreactor the ideal scale-up system for processes under cgmp. bio-t xpac The multi-bioreactor system for research and development at the highest level. bio-t production plant Individually tailored for the customer s process and constructed as a package unit or as a complex production plant.

4 bio-t mini the laboratory bioreactor system As the smallest member of the zeta family, the bio-t mini laboratory reactor system is designed for conventional research and development tasks, and also as a training system for universities. The bio-t mini s control system is based on a PC-compatible processor system. An 8 colour touchscreen serves as the user terminal, allowing for intuitive operation of the entire system. Within a compact stainless steel cabinet, the control unit houses all of the modules required for operation of the bio-t mini reactor, and can be operated with autoclavable culture vessels with a working volume of up to 10 litres. All common processes are supported by Universal lid nozzles for inserts, such as dip tubes, addition ports, exhaust gas cooler, sensor equipment Exhaust gas cooler, even in the fold-down version Magnetic coupling for agitators and spin filters Gas filter holders for head space gas supply / gas suppliers Gas supply by means of cascade control (gas mixture / speed / pressure / feed) Four freely configurable peristaltic pumps Connection of external pumps and scales for fed-batch or continuous fermentation Integrated, high-performance heating circuit

5 Separate supply of gas to the reactor content above the head space and gas suppliers are offered as one of the possible options. The gas mixing station can be provided in two variants. Digital gas mixing effective and cost-efficient air / nitrogen / oxygen / carbon dioxide with solenoid valves Analogue gas mixing precise dosing and exact mass balancing air / nitrogen / oxygen / carbon dioxide with mass-flow controllers AMRi with internal magnetic coupling. The tasks facing agitator equipment in bio-process technology are widely varied in their nature and are always designed by our engineers to respond to the specific process. Accordingly, they correspond to the various requirements in respect of reducing temperature and concentration gradients, dispersing gas volumes introduced and the suspension of cells and solid materials within the reaction system. AMRi is the solution for bioreactors in the laboratory or technical centre. It requires less in the way of torque to be applied, in this way permitting a simpler construction while still fulfilling high requirements in terms of sterile design. An outstanding feature here is the encapsulated magnetic coupling projecting into the product space, and the ceramic shaft bearing in a version with no clearance volume. Apart from magnetic-coupled agitators, zeta also supply conventionally-sealed agitator systems with a single or double mechanical seal. These are used mainly where the risk of contamination is more of a secondary consideration.

6 bio-t xpac Multi-bioreactor systems for demanding processes in R&D The xpac multi-bioreactor system provides an excellent example of effective screening, systematic process development and realistic process scale-up. Working on the basis of our know how as plant constructors, we develop multi-bioreactor plants in response to the demands of industry, in this way also providing the ideal fermentation tool for the demanding scientist and engineer. The xpac system is an uncompromising solution for all fermentation tasks and, as it is engineered individually within our own production operation it can be designed either as a reactor for bacteria fermentation or for propagating cell cultures. At the same time, the system is particularly suitable for use in a GMP environment and as a production system for producing active agents in small quantities, for clinical studies, for example. The basic device includes the necessary installations for the content of the reactor in terms of setting temperature, mixing and the supply of gas. All parameters can be controlled independently of each other and the individual reactors are all supplied separately with media, thus guaranteeing maximum flexibility in the process.

7 The outstanding features of xpac are: Double-wall culture vessels with process-specific H/D ratio and working volumes of 0.5 to 5 litres Bottom or top-mounted magnetic agitator with impellers adapted for the process, speed ranges of 15 to 1500 rpm Gas supply by means of various gas-supplier versions and headspace, exhaust gas cooler are available if desired in fold-down version (space-saving version for laboratory autoclaves) Integration of any number of probes desired, mass-flow controllers, rotameters, pumps, scales, etc. Compact design, available in mobile or stationary version Complex regulation strategies simple to implement and programme by means of menu-driven control system Downstream equipment can be integrated seamlessly into the design of the overall system in terms of both hardware and software Individual control and data recording for the relevant reactors If desired, control system in compliance with 21 CFR Part 11 Comprehensive qualification possible in accordance with cgmp and GAMP

8 bio-t pro Fill the gap between laboratory and production For most biotechnologists involved in either basic research or development close to the production stage, scale-up and adherence to the original concept are of crucial importance. The bio-t pro series has been developed to take these two aspects into account while still retaining the industrial concept, prefabrication as a skid unit and 3D-based modularisation of the individual functional units. With its standardised reactors, working volumes of from 10 to 500 litres and a height to diameter ratio of 2:1 or 3:1, this series represents the ideal tool for process development, from the initial experiment through to small-scale production. The reactor vessels allow for maximum flexibility with a large number of nozzles and a large selection of accessories for every conceivable application in the field of bioprocess technology, such as: Gas mixing station and spin filter for cell culture technology Automated CIP equipment Tanks sterilisable in-situ, or re-sterilisable bag connections Retractable probes for ph or po 2 Cover lifting device in manual or motorised version An additional useful accessory for the bio-t pro is the mechanical fufo foam separator which applies centrifugal force to separate out the gas from the liquid phase at the rapidly rotating turbine, thus eliminating problematic foam. The liquid phase is channelled back into the reactor and the gas eliminated through the outgoing air filter. By keeping the requirement for chemical anti-forming agents to a minimum, fufo presents itself as the ideal device for many fermentation processes. Given the trend for high value / low volume active agents, production can already be commenced in a relatively small-volume bioreactor, in the laboratory or technical centre.

9 bio-t pro s evolution control system is based on the Simatic S7-300 industrial hardware and a SCADA system to provide visualisation and data recording functions (WinCC). Where required, pre-configured software packages are individually tailored in response to individual requirements. The list below is a non-comprehensive selection of functions available: All standard measured values for bioprocess technology Acoustic and visual alarm identification and recording Software calibration of probes and dosing pumps Formulation processing Various sequences and safety links configurable Master / slave functions and set-point ramps can be implemented Password protection with access hierarchy, automatic logging of user interventions and data recording (in compliance with 21 CFR Part 11) Integration of any number of bioreactors desired, along with additional process equipment, for example CIP, ultra-filtration and medium / harvesting vessels Self-diagnostics test on operational start-up From the simple skid through to the complex system, from media transfer through to difficult sequences and safety links: with the superb performance of bio-t pro s evolution control system, all requirements are fulfilled, thus guaranteeing that the system and bio-processes are represented faithfully and in simple to control form.

10 Plant construction at the highest level Soundly-based engineering, fully thought out constructions and professional project management provide the foundation for the construction of biotech plants. Many references in respect of the various upstream processes document our competence in the individual production and ongoing maintenance of a culture of customised designs : Production plants for processes using cell cultures, bacteria and fungi Production of vaccines using cell cultures and bacteria Anaerobic fermentation with enhanced safety requirements Biomass extraction in the field of food technology Systems for development departments and training centres close to the production stage

11 Taking as our starting point basic engineering, user requirements and technical specifications, we convert your ideas into a concept from which we develop the detailed engineering with a complete 3D plan, construct the individual components such as vessels and agitators and produce the functional specification for programming the control software. Well-established project management software tools are the common factor running through all zeta projects. As early of the development phase, the interaction between various components and functions within the entire system must be investigated. For example, both of our experimental reactor stands can be designed for a scale of either 5 to 10 litres or 400 to 750 litres. Apart from practical trialling in the technical centre, our engineers can also call on software tools (CFD computational fluid dynamics) to help them work out the relevant theoretical principles. The finished plant is the result of interdisciplinary cooperation between process technicians, engineers and automation specialists within the zeta Group. With this smooth interaction of competences, we guarantee that our customers specifications will be fulfilled faithfully and in good time.

12 Automation Today, success and progress in process technology are determined by sophisticated automation systems. The evolution automation system has been specially adapted for fermentation processes, offering the operator all of the necessary functions. The system is scalable, from simple process visualisation and regulation functions through to fully-automated operation of the process, with a batch management system and recording in accordance with 21 CFR Part 11. The evolution system family is used in all areas of process technology. All the documents and procedures required for validation in accordance with GAMP 4 can also be supplied as an option. 6.1 Visualisation The basic version of evolution offers ergonomic process visualisation, providing the operator with an optimum overview of all of the relevant process parameters and values measured online. The software package includes the following functions Process visualisation Setpoint control, setpoint profile Cascade controller Timer Trending Alarm logging Calibration tool According to the version, functions such as Automatic CIP/SIP Fed-Batch programmes Weighing functions can be integrated or retrofitted.

13 6.2 Data Management The Data Management software package offers a variety of recording and archiving functions. Archiving of process data and parameters Archiving of measured values and trend curves Export of process data for external post-processing Loading and storage of process parameter sets (recipes) Fermentation and CIP/SIP reports The evolution system platform provides all the features needed for complete data management, independent of external systems. 6.3 Batch Management The Batch Management software package allows batch processing compliant with ISA S88. All program processes such as CIP, SIP and filtration are defined and processed as recipes. The operator assembles the recipes from defined process phases. Batch Editor Batch Manager Report Manager ccmp reports (only with the Auditrail option) Compliance with 21 CFR Part Industry-standard hardware The evolution system is based on standard components originally designed for industrial use, and are available throughout the world. Features of the system: Touchscreen operation Powerful panel PC Windows-XP Pro Client-Server compatible Communication via TCP/IP

14 More about us Additional information 7.1 Production of skids and plants, installation and service available at all times As part of the zeta Group, the Bio- and Processtechnology Division has production plants in Switzerland, Germany and Austria. Additional locations and representative agencies in Europe and the USA guarantee that service is constantly available and that spare parts can always be supplied for existing plants. As stainless steels are the only materials processed in all of our workshops, this reliably prevents any contamination of outgoing materials, while our comprehensive system of material and production management guarantees that the required quality requirements and customer specifications are adhered to. The following standard materials are used in our laboratory systems, skids and plants: In product contact: stainless steel , if desired, ferrite content under 1 % Not in product contact: stainless steel Seals EPDM, FDA compliant, borosilicate glass, ceramic bearing in silicone carbide and zirconium oxide Surfaces in product contact ground to Ra 0.8 µm and electro-polished, if desired also ground to Ra 0.2 µm and electro-polished However, most special materials can also be processed for specific projects, for example and (Hastelloy)

15 7.2 Services for efficient plant validation The stringent requirements of our customers are not restricted to the technical and functional aspects of a component or plant. Anyone wishing to fulfil the strict requirements of the FDA and producing in compliance with cgmp is justified in demanding that his supplier provide the same high standard in terms of quality assurance for his engineering and production operations. For us, it goes without saying that we produce the necessary DQ / IQ / and OQ documents and validate our plants in accordance with them. We have developed our own GMP-compliant document management system in-house to support us in this work. In addition, if you so require, our specialists can produce the necessary IQ / OQ documents for entire systems for you and carry out a complete validation procedure on your behalf, or also provide you with assistance with PQ. The qualified approach we apply ensures that validation can be carried out in good time, successfully and within the planned costs.

16 Bio- and Processtechnology Sterile Plant Construction Automation zeta AG Bio- und Verfahrenstechnik CH-8640 Rapperswil, Alte Jonastraße 83 Phone: +41 / 55 / Fax: +41 / 55 / office@zeta.com R 0506 E zeta s core competences are engineering, production, automation and installation of turn-key production plants, media systems and high-tech process equipment. We supply products and services to customers in the biotech and pharmaceutical sector and in the food and cosmetics industry around the world. Evolution of Technology