Complex Solutions in Modular Design

Laboratory automation has significantly changed chemical and pharmaceutical research since the 1980s. Complex automation and handling solutions provided by Bosch have proven successful in chemical laboratories for a long time. Bosch Packaging Technology is now transferring its concept of lab automation and handling to the pharmaceutical market. Based on its packaging and pharmaceutical know-how, Bosch offers the pharmaceutical industry highly flexible, tailor-made solutions along the value chain.

Mixing, stirring, dosing, applying – regardless of the outcome, a machine maps certain processes. These may lead to the production of varnishes, pesticides, glues, or pharmaceutical formulations. The pharmaceutical industry can learn and benefit from these kinds of procedures and systems, which have already been successful in chemistry for some time. As pharmaceutical laboratories continuously automate their processes, the need for individual solutions and complex special-purpose machinery is also on the rise. Bosch Packaging Technology develops and markets high-throughput technologies and lab automation for a fast and efficient development of new materials and formulas. The aim is to transfer customized development processes into industry-standard, highly flexible and modular automation solutions for the pharmaceutical market – from fundamental research to product and quality control.

Higher Throughput, Faster Product Development
Over many decades, chemical and pharmaceutical laboratory technicians have developed samples in numerous manual trials. Methods from combinatorial chemistry triggered major changes, which are especially important for the development of new medicines. Automation has simplified processing operations and significantly increased the reproducibility of trial results. Automated processes and experiments can now be carried out simultaneously. They can also be repeated as often as required with comparatively small effort. This leads to a significant improvement of results. Until present, Bosch has primarily supplied its automation solutions to the chemical market with its special needs, for instance, for high viscosity or temperature.

Meanwhile the pharmaceutical industry also requires new solutions which exceed current standards. Bosch can resort to an extensive experience with highly potent substances in the chemical and pharmaceutical industry. Automated laboratory procedures give users access to a wide spectrum of processes and analytical opportunities. Thanks to the large amount of available samples, automated processes now lead to the final product much quicker. Moreover they considerably reduce the use of raw material. Solutions for lab automation such as Bosch’s system for “high-throughput synthesis and screening” quickly lead to higher performance. In the chemical industry, automation increases lab efficiency by a factor of approximately 2.5. This corresponds to a reduction of 60 percent in terms of time and costs. The automated lab offers a further important advantage: “Useful reactions and process parameters are often not found by manual formulation tests. The manual lab classifies some additives as ‘not exploitable’ and eliminates them. However, automated test series reveal how useful these additives are in combination with other compounds, for example when testing the solubility of active substances,” explained Dr. Thomas Brinz, chemist at Bosch Packaging Technology.

New Patented Formulation Technology
The patented BLS (Bosch Lab Systems) syringe was originally developed by Bosch for the chemical industry. But it also promises great improvements to pharmaceutical labs: Together with the powder formulation, also patented by Bosch, it forms the basis for the formulation technology. In both chemistry and pharmacy, liquids with different viscosities, pigments and additives serve as raw materials for the mixture. Traditional dosing technologies apply these liquids by sucking in the material. However, they do not process media with high viscosity. The patented BLS syringe greatly facilitates this procedure, because its cylinder can absorb media with different textures. By using a piston with separate outflow, the syringe becomes a very precise dosing device.

Raw material container and reaction process vessel are both integrated in the airlessly filled syringe. The same syringe can be used for developing and applying formulations in order to test the properties under realistic conditions. This enables the production of highly complex formulations such as oil/water emulsions. The disposable syringe not only eliminates cleaning efforts. It also significantly reduces the amount of liquid waste.

Modules Flexibly Combined
Bosch’s portfolio also includes larger machines, which make handling a lot easier. By moving along the linear axis, handling robots carry out highly complex actions. The robots are adapted to customers’ needs with a combination of standardized and flexible modules. The technological foundation of these modular combinations is key for their flexibility: based on a modular construction system, the required components are connected with each other to form customized solutions. This modular concept enables Bosch to offer complex special constructions, combining different assembly groups along the value chain. They range from fundamental research to quality control, and include the integration of external customer-owned processes.

Bosch uses its own lab and system control software Workflow-Manager to smoothly coordinate and control all processes. Each machine element is operated via a PLC (Programmable Logic Controller) module. The flexible software can control machines, lab and measuring equipment, as well as individual work places. Apart from developing the technology, Bosch also tests various applications for customers. Feasibility studies answer the following questions: How do production processes match? How can specific manual processes be automated in the lab? How can industrial processes be transferred to laboratory scale?

Focusing on the Pharmaceutical Industry
Over the last years, this lab automation concept has been successfully implemented in the chemical industry many times. For example, Bosch cooperated with BASF in the development of high-throughput screening equipment for varnish. Up to 100 different types of varnish systems can be processed within a very short time. Considering the broad range of varnish systems that needed to be examined, Bosch’s BLS syringe dosing system was the key to success. The system was awarded the ‘Farbe und Lack Preis’ for its environmental friendliness in 2005.

These achievements have now also entered the pharmaceutical market: “The pharmaceutical industry focuses on the medicinal and chemical design of small molecules and their biological testing for active ingredient research. We use automated systems to replace the traditional manual and repetitive tasks in chemical synthesis, filtration or analytics by new processes and innovative technologies,” said Stefan Oberbörsch, Head of Medicinal Chemistry Technologies at Grünenthal GmbH in Aachen, Germany. Another user of these specific solutions from Bosch is Eurofins MWG Operon, headquartered in Ebersberg near Munich, provider of services for DNA, RNA and gen syntheses as well as sequencing, applied genetics and forensics. The company uses a robot for storing and sending DNA samples.

Bosch Packaging Technology has recently enhanced its competencies in the pharmaceutical industry along the value chain, and has increasingly positioned itself as a supplier of all-in-one solutions. Consequently, Bosch can revert to a broad expertise and can combine modules from different sections depending on customers’ requirements. This includes the manufacturing and packaging of pharmaceuticals, as well as inspection technology. Thanks to many years of experience in the chemical industry, Bosch can integrate customers’ own processes and complete them by its own competencies in lab automation and handling. This allows Bosch to build extremely flexible custom constructions that meet a growing need in the pharmaceutical industry – with reasonable effort and simultaneously workable modules.