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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 PHARMACEUTICALINDUSTRY

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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 compre-hensive optimisation and automation of the equipment and the production of liquid, semi-solid and solid pharmaceutical products in one place.

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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 cer-tified by reputable European certifying agencies (TÜV, EHEDG).The professional knowledge and the many years of experience of our expert team are a guaran-tee 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 con-sumer and to fully prepare your respected company for future process challenges.

ABOUT US

Designers and Production Technologists Design and Process Engineers Project Managers Automation Engineers Quality Assurance Research and Development Overhead services

Production and logistic

EMPLOYEE STRUCTURE

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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 compo-nents of process systems for the pharmaceutical industry in one place and the assurance of the compatibility of turnkey process solutions.

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PROCESS SYSTEMS PROCESS SYSTEMS

Wehaveextensiveexperienceinprocesssystemsfortheproductionofliquidpharmaceuticalsubstances:

• Parenterals• Solutions• Suspensions• Emulsions

Weinparticularlydealwithprocesssystemsfor:

• 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 techni-cal area as modular units with a minimum time of instal-lation and optimum occupancy of space. Our advantage is the automation of cleaning, sterilisation and drying processes.

CoMPoUNDINgSYSTEMSfoRLIqUIDS

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Flexible preparation oF pellet coating liquids

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.

preparation oF injection solutions

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.

syrups

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.

PROCESS SYSTEMS

CoMPoUNDINgSYSTEMSfoRLIqUIDS

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forthedesignofointmentsandcreamsproductionprocesssystems,weatBrinoxfocusparticularoninnovationsforprocessesforthedispersionanddissolutionofactiveingredientsandthereductionofthedispersiontime.

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 uni-form 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 tempera- tures and low pressures. • Innovative procedures for quick and easy emptying of viscous melt from a reactor.

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.

Wehavemanypositiveexperiencesinthefieldofsub-stancecompoundingsystemsforsolidpharmaceuticalpreparationsatveryhightemperaturesandlowpres-suresandwithaninnovativeprocedureofquickandeasyemptyingofviscousmeltfromthemixingvessel.ourinnovativedrying,granulationandcoating/layeringequipmentcanmeethighestrequirementsforproductqualityandprocessflexibility.

PROCESS SYSTEMSPROCESS SYSTEMS

PRoCESSINgTECHNoLogIESfoRSoLIDSCoMPoUNDINgSYSTEMSfoRSEMISoLIDS

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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 numer-ous experiences in the prepa-ration of all types of pharma-ceutical 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 sys-tems, 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 pro-cess units and the occupancy of a given technical area.

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PROCESS UNITS

Wedesignandmanufactureallkindsofmixingandreac-torvesselssuitableforprocessesofmixing,inertisation,vacuumising,meteringandemptying.

PROCESS UNITS

PRoCESSVESSELSANDREACToRS

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pure steam generators

We manufacture skid Pure Steam Generators of various capacities.

Wedesignandmanufacturealltypesofpharmaceuticalwaterpreparationunits.

• PWsystems• WfIsystems• PureSteamgenerators

pW preparation units

Brinox PW units ensure quality in accordance with Euro-pean and U.S. Pharmacopeia.

Pre-preparation:• Ultrafiltration• Softening equipment (K)Preparation:• Ion exchangers (A+K)• RO (reverse osmosis)• EDI (continuous electro deionisation)

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PROCESS UNITS

PHARMACEUTICALWATERPREPARATIoNUNITS

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Energyprocessunits(usuallya‘skid’)areaspecialin-novationthatincludes:

• Heatingsystems• Coolingsystems• Vacuumising• CIP/SIP/DIPprocesses

Wedesignandmanufactureskidunitswhichallow:

• fastinstallationonsite• Simpleanduserfriendlyoperation• optimalspatialinstallationofthecomponents

Accordingtotheirfunction,theyarecompletelycustomizedunitswiththeoptionofcompleteautomation.

cip - sip - dip units

CIP Brinox units are automated and enable optimal clean-ing 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.

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PROCESS UNITS

SkIDUNITS

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PROCESS UNITS

SkIDUNITS

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

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 ma-chine equipment.

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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.

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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 dimen-sional stability of containers and welds of exceptional quality.We have introduced a special chemical cleaning process, which involves removing all impurities and assures pas-sivation of stainless surfaces after welding and grinding.

PROCESS COMPONENTS PROCESS COMPONENTS

TUBEHEATExCHANgERS IBCCoNTAINERS

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In the development of new process solutions, we use modern scientific approaches and collaborate with re-nowned 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 opera-tional 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.

BUSINESS ACTIVITIES

With the management of modern technology and produc-tion 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 de-termine 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 valida-tion 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 defini-tion 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 de-veloping 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 com-ponents provide compatibility of turnkey process solution anywhere and at anytime all in one place.

→  research and development → process engineering → conceptual design → basic engineering → implementation engineering →  production and implementation

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BUSINESS ACTIVITIES

→  automation → tests and measurements → assembly → validation → maintenance ↓

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 addi-tional stricter requirements for achieving quality stand-ards to Brinox process solutions. Our department for quality assurance, which eliminates in advance potential errors in the operation of our produc-tion components with mid-phase and final tests and measurements, provides quality control at all levels of the production system.

Our team of highly qualified fitters and implementing engineers provide professional assembly and the correct execution of the process solution.

On the client’s request, Brinox can assist in the imple-mentation of validation procedures of installation and op-eration 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

• DottikonExclusiveSynthesisAg,Switzerland• HemofarmA.D.,Vršac,memberoftheStadagroup, Serbia• krka-PolskaSp.z.o.o.,Varshawa,Poland• krka,d.d.,Novomesto,Slovenia• krka-farmad.o.o.,Zagreb,Croatia• oookrka-Rus,Istra,Russianfederation• Lek,pharmaceuticalcompany,d.d.,Ljubljana, memberoftheSandozgroup,Slovenia• Marifarmd.o.o.,Maribor,Slovenia• Merckgroup,germany• PfizerManufacturingBelgiumNV,Puurs,memberof thePfizergroup,Belgium• SandozgmbH,kundl,memberoftheNovartisgroup, Austria

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SELECTEDREFERENCESDottikon 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, Russianfederation • 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

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BRINoxd.o.o.Sora 21, SI–1215 MedvodeSloveniatel +386 1 361 97 30 fax +386 1 361 97 20 info@brinox.euwww.brinox.eu

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