V e r i f i e d S o l u t i o n s f o r P r o c e s s C h a l l e n g e s PHARMACEUTICAL INDUSTRY 1
PHARMACEUTICAL INDUSTRY With innovation and quality, we realize the most demanding needs of the pharmaceutical industry in the field of personalised process systems. In accordance with the strictest technological, sanitary and quality standards, we provide a comprehensive optimisation and automation of the equipment and the production of liquid, semi-solid and solid pharmaceutical products in one place. 3
about us We are an innovative European family business with a 40-year tradition of specialising in the field of assuring fast, effective, cost competitive and tailored turnkey solutions for the complex problems of the process industry. Our vision is to become, in the long-term, the leading European supplier of personalised process solutions. More than half of our employees are highly trained engineers with years of experiences. We are certified by reputable European certifying agencies (TÜV, EHEDG). The professional knowledge and the many years of experience of our expert team are a guarantee for the comprehensive offer of entire process systems, individual units and components for the pharmaceutical, chemical and food-processing industry. In Brinox, we face new challenges in process engineering with optimism based on experiences, knowledge and professionalism. At the same time we show our flexibility, so that we are not only moving with the times and the local environment in which we operate, but that we can anticipate complex process problems and that we can globally respond to them quickly and effectively. We accompany you the entire way from a problem to a comprehensive process solution tailored to your needs in order to develop process improvements for the smooth operation of your production and provide you with the necessary competitive advantage. Confide us your process requirements and allow us to improve the quality of life of your end consumer and to fully prepare your respected company for future process challenges. Employee structure Designers and Production Technologists Design and Process Engineers Project Managers Automation Engineers Quality Assurance Research and Development Overhead services Production and logistic 5
Process systems Our hallmark is to provide fast, efficient and cost-competitive turnkey tailored solutions for the complex problems for the pharmaceutical industry. The competitive advantage of the Brinox business approach is the ability of independent design, manufacture, assembly and automation of key components of process systems for the pharmaceutical industry in one place and the assurance of the compatibility of turnkey process solutions. 6 7
Process systems Process systems Compounding systems for liquids We have extensive experience in process systems for the production of liquid pharmaceutical substances: Parenterals Solutions Suspensions Emulsions We in particularly deal with process systems for: Metering Mixing Heating Cooling Vacuumising Flexible production of parenterals The innovative benefits of Brinox process systems are production lines with a batch size range from 10% to 100% of nominal size. The main processing units are typically implemented as fixed or mobile reactor or mixing vessels. The auxiliary (e.g. energy) units are installed in the technical area as modular units with a minimum time of installation and optimum occupancy of space. Our advantage is the automation of cleaning, sterilisation and drying processes. 9
Process systems Compounding systems for liquids Preparation of injection solutions flexible preparation of pellet coating liquids Syrups Characteristics of the Brinox process systems: In-line sterilisation of the pre-filter and sterile filter with clean saturated steam (SIP). In-line automatic rinsing of the pre-filter and sterile filter with water for injections before sterilization and for inline filter integrity testing. The solution passes steadily through the filters and prevents early clogging of the filter inserts. The storage tanks have the same volume as the main mixer. The filter unit (including the filtration housing) is automatically purged. In-line integrity test of the sterile solution filter or the filter for sterile filtering of inert gas. Additional options: Drying of the entire filtration unit with sterile filtered inert gas (DIP). An additional filter for the sterile filtering of inert gas can be incorporated into the process of a SIP filtration unit and provided with sterilisation and drying with a sterile solution filter. Our process solutions are distinguished by: A special system of in-line metering, which optimises the intermixing time of slowly soluble components. The use of larger fixed and smaller mobile mixing vessels. Special flexible connections where required. For syrup production systems, we focus on: Optimisation of production time and safety (recipe). Increase of product quality (dispersion). Increase of product stability (tempering). Automatic metering of raw materials. 11
Process systems Process systems Compounding systems for semisolids Processing technologies for solids For the design of ointments and creams production process systems, we at Brinox focus particular on innovations for processes for the dispersion and dissolution of active ingredients and the reduction of the dispersion time. We have many positive experiences in the field of substance compounding systems for solid pharmaceutical preparations at very high temperatures and low pressures and with an innovative procedure of quick and easy emptying of viscous melt from the mixing vessel. Our innovative drying, granulation and coating/layering equipment can meet highest requirements for product quality and process flexibility. Ointments, creams and emulsions In the design of process systems for the production of ointments, creams and emulsions we are especially interested in: The introduction of the most contemporary processes for dispersion and the dissolution of active ingredients. Reducing the dispersion time. Automatic CIP/DIP systems. Fluid bed technology for granulation, drying and pellet or tablet coating Brinox can supply a single fluid bed unit or system with interchangeable modules. Our Wurster coater with novel, patent pending swirl flow generator can achieve uniform coating thickness regardless of pellet size and can improve coating process yield. Our latest patent pending fluid bed processor gives multiple processes in a single process chamber. Pastilles We have extensive experience in the field of: Systems for mixing substances at very high temperatures and low pressures. Innovative procedures for quick and easy emptying of viscous melt from a reactor. 12 13
Process units In addition to designing and implementing entire process systems, Brinox can at the customer's request design and implement individual process components. We are distinguished by numerous experiences in the preparation of all types of pharmaceutical water and cleaning systems, sterilisation and drying of production equipment in pharmaceutical industry. Our energy process units are a special innovation that includes heating systems, cooling systems, vacuumising and CIP / SIP / DIP processes. Thus, we combine comprehensively and in one place all the important parts of auxiliary equipment, installed in the usually scarce technical areas. In this way, we optimise the installation and assembly time of energy process 14 units and the occupancy of 15 a given technical area.
Process units Process units Process vessels and reactors We design and manufacture all kinds of mixing and reactor vessels suitable for processes of mixing, inertisation, vacuumising, metering and emptying. 16 17
Process units Pharmaceutical water preparation units We design and manufacture all types of pharmaceutical water preparation units. PW systems WFI systems Pure Steam Generators PW preparation units Brinox PW units ensure quality in accordance with European and U.S. Pharmacopeia. Pre-preparation: Ultrafiltration Softening equipment (K) Preparation: Ion exchangers (A+K) RO (reverse osmosis) EDI (continuous electro deionisation) Pure Steam Generators We manufacture skid Pure Steam Generators of various capacities. 18 15 19
Process units Skid units Energy process units (usually a skid ) are a special innovation that includes: Heating systems Cooling systems Vacuumising CIP/SIP/DIP processes We design and manufacture skid units which allow: CIP - SIP - DIP units CIP Brinox units are automated and enable optimal cleaning time and detergent use with the best cleaning effect. An option of sterilisation and drying is also possible (CIP/ SIP/DIP). They are designed in accordance with the requirements of repeatability and optional cleaning validation. Fast installation on site Simple and user friendly operation Optimal spatial installation of the components According to their function, they are completely customized units with the option of complete automation. 14 20 21
Process units Skid units Metering units for organic solvents Brinox developed special metering units for the use of organic solvents in the compounding lines for coating components. They are designed in accordance with the ATEX and other directives in the area of electric and machine equipment. Universal auxiliary power units Brinox innovation is that one frame combines individual units: CIP/SIP/DIP Heating-cooling unit Vacuum unit This enables: Fast and effective installation A greater degree of flexibility in operation Optimal use of space 22 15 23
Process components Brinox manufactures certain process system components, e.g. hygienic valves, tube heat exchangers and IBC containers as well. The components are manufactured with exceptional accuracy, which ensures operation virtually without any stopping and with minimal maintenance costs. 24 25
Process components Process components Tube heat exchangers IBC Containers We construct and manufacture hygienic tube heat exchangers in accordance with cgmp, ATEX and PED directives. A special version with a double flange ensures that there will be no mixing of the heating or cooling medium with the pharmaceutical liquid, which prevents the possibility of contamination. Robotic welding and grinding provide exceptional dimensional stability of containers and welds of exceptional quality. We have introduced a special chemical cleaning process, which involves removing all impurities and assures passivation of stainless surfaces after welding and grinding. 26 27
BUSINESS ACTIVITIES Research and development process engineering Conceptual design Basic engineering Implementation engineering Production and implementation In the development of new process solutions, we use modern scientific approaches and collaborate with renowned local and foreign research institutions. In our department for development, we employ highly educated experts from the fields of pharmacy, chemical and mechanical engineering and automation. In the procedure of process engineering, we design the required components and determine the necessary operational conditions at all stages of their life cycle. At the customer s request, we will also participate in the validation procedure of the installed equipment. We acquire and manage all the necessary documentation for the installed equipment. With the management of modern technology and production processes and the high qualifications of our expert team, we can always offer the necessary innovation in designing process solutions for entire process systems or individual production units and components. In the procedure of process engineering, through the stages of conceptual design, basic and implemental engineering, we design the required components and determine the necessary operational conditions of turnkey process solutions at all stages of their life cycle. At the customer s request, we will also participate in the validation procedure of the installed equipment. We acquire and manage all the necessary documentation for the installed equipment. The main tool of basic engineering is the precise definition of the functionality of process systems and the links between them. The process flow chart (P & ID diagram), tailored to customer s needs is basic document for developing system control schemes, the physical sequence of equipment and individual systems and a platform for further safety and operational research. Implementation engineering is a special type of privilege. An expert team dedicates itself with high precision to the turnkey process solution even before it is implemented. In this way, with great devotion, we significantly reduce potential process risks and find a way for our solution to complex production problems to fulfil all specified user requirements and to be in accordance with applicable guidelines, standards, and cgmp. In addition to implementation engineering, our own production and assembly of key process components for entire process systems or individual units at the client's location is another speciality of Brinox process systems. In this way, we can challenge production limitations and with our own production and assembly of process components provide compatibility of turnkey process solution anywhere and at anytime all in one place. 28 29
BUSINESS ACTIVITIES Assembly Automation Tests and measurements Validation Maintenance Our team of highly qualified fitters and implementing engineers provide professional assembly and the correct execution of the process solution. In accordance with the requirements for your process system, we can provide a comprehensive automation solution that: Is based on the ISA S88.01 standard for batch rocesses and the 21CFR part 11 guidelines on electronic records and signatures. Is based on PLC-SCADA open solutions. Takes into account GAMP 5 guidelines on project life cycle. Uses established technologies for process management (Siemens, GE, and Microsoft). Provides reporting, recipe management and connection with superior MES systems based on an integrated SQL database. Quality is our personal signature, which prescribes additional stricter requirements for achieving quality standards to Brinox process solutions. Our department for quality assurance, which eliminates in advance potential errors in the operation of our production components with mid-phase and final tests and measurements, provides quality control at all levels of the production system. On the client s request, Brinox can assist in the implementation of validation procedures of installation and operation of the designed process equipment and systems. We can provide our business partners with: Intervention, repair and assembly Spare parts for our equipment Engineer supported interventions for any possible alterations Continuous education and training for the operation of process based solutions SELECTED REFERENCES Dottikon Exclusive Synthesis AG, Switzerland Hemofarm A.D., Vršac, member of the Stada Group, Serbia Krka-Polska Sp. z.o.o., Varshawa, Poland Krka, d. d., Novo mesto, Slovenia Krka-Farma d.o.o., Zagreb, Croatia OOO Krka-Rus, Istra, Russian Federation Lek, pharmaceutical company, d.d., Ljubljana, member of the Sandoz Group, Slovenia Marifarm d.o.o., Maribor, Slovenia Merck Group, Germany Pfizer Manufacturing Belgium NV, Puurs, member of the Pfizer Group, Belgium Sandoz GmbH, Kundl, member of the Novartis Group, Austria 30 31
selected REFERENCES Dottikon Exclusive Synthesis AG, Switzerland Hemofarm A.D., Vršac, member of the Stada Group, Serbia Krka-Polska Sp. z.o.o., Varshawa, Poland Krka, d.d., Novo mesto, Slovenia Krka-Farma d.o.o., Zagreb, Croatia OOO Krka-Rus, Istra, Russian Federation Lek, pharmaceutical company, d.d., Ljubljana, member of the Sandoz Group, Slovenia Marifarm d.o.o., Maribor, Slovenia Merck Group, Germany Pfizer Manufacturing Belgium NV, Puurs, member of the Pfizer Group, Belgium Sandoz GmbH, Kundl, member of the Novartis Group, Austria p e r s o n a l i z e d S O L U T I O N S BRINOX d.o.o. Sora 21, SI 1215 Medvode Slovenia tel +386 1 361 97 30 fax +386 1 361 97 20 info@brinox.eu www.brinox.eu PH201011 EN photo: Marko Prezelj, istockphoto, 3, 12, production: SIDARTA 33