TECHNOLOGY THAT DELIVERS

PHARMACEUTICAL
INDUSTRY
TECHNOLOGY THAT DELIVERS
30 YEARS OF INNOVATIONS
“More than thirty years of experience in the pharmaceutical
and food industry are a guarantee for flawless process
systems.”
We are an innovative European company
specializing in fast, efficient, cost competitive
and personalized process systems.
We focus our knowledge and competences
on the development and production of
high-tech equipment for the most complex
requirements of the pharmaceutical industry.
In compliance with national and international
norms and standards, based on GMP and
FDA directives, we provide personalized
turnkey solutions in the fields of:
• Biotechnology: upstream plants,
downstream plants, formulation plants,
• Pharmaceuticals: API synthesis plants,
sterile plants, liquid, semisolid and solid
dosage forms plants.
Our long-term vision is to become the
leading European provider of unique,
personalized process solutions.
3 PHARMACEUTICAL INDUSTRY
More than 200 motivated and highly
educated employees follow the company's
values, which are based on our customers'
requirements regarding:
> quality,
> innovation,
> flexibility,
> reliability.
PERSONALIZED SOLUTIONS AND RELIABLE OPERATIONS
“Every project is different. Every solution is unique.
Ideas turn into life. BRINOX, personalized solutions."
7 PHARMACEUTICAL INDUSTRY
PHARMACEUTICAL INDUSTRY COMPETENCES
ONE–STOP–SHOP APPROACH
Complex process challenges demand a
customized approach. Brinox high-tech
process solutions are adapted to the
specific needs of your process and aimed at
improving your process systems’ efficiency,
maximising your competitiveness whilst
respecting the project’s boundaries and
ensuring full compliance with cGMP.
The heart of the company lies in our team,
which is composed by a winning mix of
experienced members on one hand, and
young and ambitious experts, combining
excellent craftsmanship with the most
advanced technologies at all stages, from
engineering till validation.
With a ˝one-stop-shop˝ approach we
provide a full range of solutions for the most
advanced pharmaceutical facilities and
equipment:
9 PHARMACEUTICAL INDUSTRY
“We offer turnkey solutions to our customers in the
pharmaceutical industry: from conceptual design to
implementation and automation."
• Consulting: cGMP compliance, facilities
and equipment productivity, sustainability.
• Process engineering: conceptual design,
basic design, detail design.
• Implementation: manufacturing, quality
control, logistics, assembly, automation.
• Validation: RA, DQ, IQ, OQ, training.
• Aftersales: maintenance, support,
retrofitting.
We will accompany you throughout the
entire way from a complex process problem
to an optimal solution, completely tailored
to your needs, be it a process system, a
process unit or even a whole production
facility.
LIQUID FORMS
ASEPTIC PROCESSING
“Our path here at Brinox started more than three decades
ago in liquids processing. That is why our experience with
liquid forms is the most extensive one.”
We have extensive experience in process
systems for the compounding of injectables:
• Ampoules,
• Vials (liquid and lyophilized),
• Syringes.
FLEXIBLE PRODUCTION OF PARENTERALS
We in particularly deal with process
systems for:
• Solvent/WFI dosing,
• Mixing, dissolution of active solids,
• Sterile filtration,
• ClP, SIP, DIP,
• Filter integrity testing in place.
The main processing units are typically
implemented as fixed or mobile reactor or
mixing vessels.
Our scope of supply also includes process
equipment for biotech applications (e.g.
harvesting vessels).
11 PHARMACEUTICAL INDUSTRY
The innovative benefits of Brinox process
systems are production lines with a batch
size range from 10% to 100% of nominal size.
The utility skids 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,
sterilization and drying processes.
LIQUID FORMS
ASEPTIC PROCESSING
PREPARATION OF INJECTION SOLUTIONS
Characteristics of the Brinox process
systems for injection solutions are:
• Aseptic compounding in the mixing vessel
according to cGMP for sterile production,
• Preparation of sterile gases for product
discharge (air, nitrogen, carbon dioxide),
• Inline filter integrity testing for the
product after sterilization and after sterile
filtration,
• Inline filter integrity testing for process
gases after sterilization,
• The solution passes steadily through the
filters and prevents early clogging of the
filter inserts,
• Discharge of the sterile product from filter
vessel to the filling line, where filter vessel
has the same capacity as the mixing vessel,
• Automatic CIP/SIP/DIP of the sterile line
where the utilization of the line is optimized
(possibility of simultaneous running with
CIP/SIP/DIP, product preparation, sterile
filtration, sterile discharge) taking into
account the process and operator safety,
13 PHARMACEUTICAL INDUSTRY
• Automation of the complete sterile
production according to GAMP5, ISA S88.01
and FDA 21CFR Part11,
• Preparation and hand-over of the
complete project documentation according
to cGMP and ISPE guidelines.
LIQUID AND SEMI-SOLID FORMS
COMPOUNDING AND BLENDING
FLEXIBLE PREPARATION OF PELLET/
TABLET COATING LIQUIDS
Our process solutions are distinguished by:
• A special system of in-line dosing, which
optimizes the intermixing time of slowly
soluble components.
• The use of larger fixed and smaller mobile
mixing vessels.
• System automation and process control
(PLC, SCADA).
• Special flexible connections where
required.
SYRUPS
For syrup production systems, we focus on:
• Optimization of production time and safety
(recipe).
• Increase of product quality (dispersion).
• Increase of product stability (tempering).
• Automatic dosing of raw materials.
15 PHARMACEUTICAL INDUSTRY
OINTMENTS, CREAMS AND EMULSIONS
In the design of process systems for the
production of ointments, creams and
emulsions our concern is:
• The introduction of the most
contemporary processes for dispersion and
the dissolution of active ingredients.
• Reducing the dispersion time.
• Automatic CIP/DIP systems.
SOLID FORMS
DRYING, HEATING AND VACUUMISING
FLUID BED TECHNOLOGY FOR
GRANULATION, DRYING AND PELLET OR
TABLET COATING
PASTILLES
Our innovative drying, granulation and
coating equipment can meet highest
requirements for product quality and
process flexibility.
• Systems for mixing substances at very
high temperatures and low pressures.
• Innovative procedures for quick and easy
emptying of viscous melt from a reactor.
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 patented fluid bed processor
gives multiple processes in a single process
chamber. A technical solution for fluid
bed drying developed by Brinox has been
awarded an European patent.
17 PHARMACEUTICAL INDUSTRY
We have extensive experience in the field of:
SOLID FORMS
MATERIAL HANDLING
We combine our process engineering
and implementation capabilities with the
capabilities of a pool of strategic partners to
provide complete material handling systems
for both vertical and horizontal processes.
We design, manufacture, install, automate
and validate solutions for the process of
dosing, weighing, blending, mixing, sieving,
transport, packing, storage and cleaning of
process components, units and systems.
We provide an expert guidance for hazardous
processes. We are focused to implement
solutions that generate less airboirne
contaminants and segregate employee from
the hazard (containment).
19 PHARMACEUTICAL INDUSTRY
“Working close with a customer for years – that develops
the partnership. This is how generally accepted technology
can even be improved.”
VERTICAL FLOW
HORIZONTAL FLOW
Brinox has successfully erected the
complete Material Handling System for
Vertical Flow, including Docking Stations,
IBC Containers and Automation of the
System. In our scope of supply a customer
can find the following:
• Feeding Docking Station (Powder+Tablet),
• Receiving Docking Station,
• IBC Containers,
• Central CIP cleaning of Docking Stations
after employment (reduction of cleaning
time, retractable spraying nozzles),
• Automation of the System (load type
recognition, integrated load cells).
For horizontal material flow Brinox has
developed several types of IBC containers
and accessories, e.g. butterfly valves. In
our scope of supply a customer can find the
following versions:
Tablet or Powder Containers: (150, 300, 800,
1200, 1400, 2400 litres),
Pilot Containers for laboratory applications:
(100 and 150 litres),
Butterfly valves with hard disc for powders
(single and double acting),
Butterfly valves with soft disc for tablets and
capsules (single and double acting) – patent
pending.
ACTIVE PHARMACEUTICAL INGREDIENTS
API SYNTHESIS
We provide complete engineering,
implementation and validation services
for API synthesis plants, using the
most advanced engineering tools and
sophisticated materials for the construction
of reactors, paddle dryers and other API
plant process units.
REACTORS
Even the smallest detail on Brinox reactors
is designed and produced with top-notch
precision and quality, in accordance with
cGMP standards and with the severest
hygienic and safety requirements:
• exclusively first class materials (Hastelloy,
Incoloy) and components are used,
• hygienic connections, no shadows for
absolutely perfect cleaning,
• dynamic and (if required) retractable
washing nozzles, with anti-locking
protection (due to sterilization) and
completely self-cleaning,
• externally mechanically polished,
internally mechanically and electropolished, as well as chemically cleaned and
passivated.
21 PHARMACEUTICAL INDUSTRY
PADDLE DRYERS – HORIZONTAL AND
VERTICAL
Brinox has developed an upgraded version
of the horizontal paddle dryer. The unique
CIP function of the machine allows in-line
cleaning after drying without disassembling,
significantly reducing the cleaning time. The
complete system is patent protected. Key
features are the following:
• The dryer´s unique shape assures space
for the positioning of spray nozzles,
• Spray nozzles are retractable, so no
disassembly before and after cleaning is
needed,
• The contained process execution allows
also the drying of high-potent media,
without extra safety measures.
Brinox provides also vertical paddle dryers,
which enable fast drying at vacuum or
overpressure conditions as well as fast dryer
discharge. The design of our vertical paddle
dryer is very compact and robust.
UTILITIES
CLEAN MEDIA PREPARATION,
STORAGE AND DISTRIBUTION
Brinox purified water preparation units
ensure consistent production of high
quality PW, in accordance with the United
States Pharmacopeia (USP) and European
Pharmacopeia (EP) regulations.
PW PREPARATION UNITS
Together with our partners we design and
manufacture all types of pharmaceutical
water preparation units:
Preparation:
• Ion exchangers (A+K),
• RO (reverse osmosis),
• EDI (continuous electro deionization).
• PW systems (storage, distribution,
sanitization),
• WFI systems (storage, distribution, SIP),
• Pure Steam Generators.
Pre-preparation:
• Ultrafiltration,
• Softening equipment (K).
PURE STEAM GENERATORS
We manufacture skid Pure Steam
Generators of various capacities.
PROCESS GASES
We also design and manufacture systems
for process gases (e.g. Nitrogen, Oxygen,
Argon, Carbon Dioxide, Compressed Air).
23 PHARMACEUTICAL INDUSTRY
UTILITIES
CIP-SIP-DIP
AND AUXILIARY PROCESSES
“When cleaning the process systems, our attention to detail
becomes even more noticeable, as outstanding systems
are also much easier to clean, environmentally friendly and
much more cost effective.”
CIP - SIP - DIP UNITS
DOSING UNITS FOR ORGANIC SOLVENTS
UNIVERSAL AUXILIARY POWER UNITS
CIP Brinox units are automated and enable
optimal cleaning time and detergent use
with the best cleaning effect.
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 (Directive 94/9/EC) and other
directives (MD 2006/42/E, EMC 89/336/
EEC, LVD 73/23, PED 97/23/EC) in the area
of electric and machine equipment.
Brinox innovation is that one frame
combines individual units:
An option of sterilization and drying is also
possible (CIP/SIP/DIP).
They are designed in accordance with the
requirements of repeatability and optional
cleaning validation.
25 PHARMACEUTICAL INDUSTRY
• 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.
OUT OF THE BOX DEVELOPMENT
CUSTOMIZED SOLUTIONS
CLEANING SYSTEM FOR CAPSULE MOULDS
Together with a market leader in capsules
production we developed a mould cleaning
system with solid advantages:
• Excellent cleaning results with an
extremely low consumption of detergents,
• Reduced consumption of all cleaning
chemicals,
• Energy savings due to lower cleaning
temperatures,
• Innovative but simple approach, new in
the market.
27 PHARMACEUTICAL INDUSTRY
“Our engineers love new challenges, which is why we are
also active in other fields. Transforming complex problems
into highly efficient process systems – that is what we
are best at!”
CLEANING SYSTEM FOR TOOTH-PASTE
MOULDS
This process system is completely
customized, including automation.
It allows shorter cleaning time and thus
faster lot changing, so the flexibility of toothpaste production increases dramatically.
There is also no need for workforce in the
cleaning chamber during the process.
Besides this, transport and clamping of
tooth-paste moulds are unique and enable
optimal CIP line adjustment.
LACTOSE DECOLOURATION
Being active also in other industries besides
the pharmaceutical one, we provide the
design and implementation of process
systems for:
• membrane filtration of whey
(ultrafiltration, nanofiltration, reverse
osmosis),
• drying of whey (proteins, lactose),
• lactose decolouration (pharmaceutical
lactose).
QUALITY ASSURANCE
“State-of-the-art measuring equipment and motivated
personnel guarantee the reliability of our process
systems, which are also thoroughly documented.”
Our QA /QC department is responsible for
quality control in all stages of the project
development.
Only top-level measuring and testing
equipment is used, making our testing lab
one of the best equipped in Europe.
We have received the following certifications:
• ISO 9001:2008,
• ISO 14001,
• ASME BPE 1997, AWS D 18.1, AWS D 18.2
and SIST EN 12732 A to D for welding works
on pressure equipment and mechanical
installations,
• DIN EN ISO 3834-3 (DIN EN ISO 3834-2),
AD 2000 HP 0 _ HP 100 R, for welding works
on pressure equipment,
• PED 97_23_EC Module A1, Module B+C1
and Module B+F, according to the PED
directive that covers pressure vessels,
reactors and heat exchangers,
• EHEDG certification (hygienic design
guidelines) for the DVEH double-seat valve,
• Hastelloy and Incoloy welding
certification.
Our approach to process design, installation
and service is in accordance with ISPE
guidelines and ASTM E2500.
29 PHARMACEUTICAL INDUSTRY
BUSINESS
ACTIVITIES
→ REGULATORY COMPLIANCE
→ R&D
→ CONCEPTUAL DESIGN
→ RISK ASSESSMENT
→ BASIC DESIGN
→ DETAILED DESIGN
→ MANUFACTURING
We share with our clients our expertise
in the field of regulatory compliance
by auditing the existing facilities and
equipment.
With the right set of tools we prepare
customised plans on how to increase the
facilities and equipment’s productivity in
compliance with cGMP requirements.
Each new project represents a new
challenge for us. A modern scientific
approach, the most advanced tools and
collaborations with established researchers
and institutions allow us to transform
each challenge into a tailor-made process
solution.
An experienced team of engineers and
technologists continuously striving for new
challenges, designs the best conceptual
solution, which is cost-effective, highperforming and GMP compliant.
Risk assessment is executed based on the
GxP, HSE, process and business influence
of the specific project. Different risk
assessment methods are used, e.g. FMEA
(Failure Mode and Effects Analysis), HACCP
(Hazard Analysis and Critical Control Points),
HASOP (Hazard and Operability Study), ZHA
(Zurich Hazard Analysis) and others.
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.
Using the most sophisticated tools we
design every process component, till the
most hidden of the details, anticipating
eventual process problems and ensuring
high efficiency and productivity.
A state-of-the-art machinery pool and
excellent craftsmanship allow us to
manufacture even the most complex
process unit and component. Having an own
workshop not only ensures a high level of
flexibility and adaptability to ever changing
demands, but guarantees also the highest
level of quality control and resect of budget
and time constraints.
→ QUALITY CONTROL
→ TESTING → ASSEMBLY
→ AUTOMATION
→ VALIDATION
→ MAINTENANCE
Our quality assurance department uses
the most advanced tools and equipment to
continuously monitor the quality within our
manufacturing system, so that potential
errors and disruptions during the operation
of our products can be discovered and
remedied in advance with the help of mid
phase and end system checks.
Brinox through its qualification procedures
makes sure the process systems and units
meet all relevant standards and regulations
and fulfil the URS. Brinox’s own testing
facility and strict test plans allow extensive
FAT prior to delivery, while Brinox’ engineers
are a guarantee for successful SAT.
Our team of highly qualified fitters
and implementing engineers provide
professional on-site assembly of our
process systems and units globally, be it
manufactured by us or by third parties.
Using only the best available tools and
equipment they make sure the equipment is
properly installed, guaranteeing its correct
functioning.
In accordance with the requirements of
the process system, we can provide a
comprehensive automation solution that:
• Is based on the ISA S88.01 standard for
batch processes 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
We offer our clients close assistance
throughout the validation procedures,
offering complete documentation support,
starting with DQ and till IQ/OQ.
Our most experienced and skilled engineers
and technicians train the client's personnel
up to a level that allows the users to fully
exploit the installed systems and units
throughout their lifespan.
We provide our clients with:
• Intervention, repair and assembly
• Spare parts for our equipment
• Engineer supported interventions for any
possible alterations
• On-line support
• Preventive check-ups
31 PHARMACEUTICAL INDUSTRY
• Uses established technologies for process
management (Siemens, GE-Fanuc, Proleit)
• Provides reporting, recipe management,
and connection with superior MES systems
based on an integrated SQL database
SELECTED REFERENCES → PHARMACEUTICAL INDUSTRY
ALCON
CAPSUGEL
GLAXOSMITHKLINE
JOHNSON & JOHNSON
KRKA
LEK
MERCK
NOVARTIS
PFIZER
PHARMSTANDARD
SANDOZ
SOTEX
STADA
TEVA
ZOETIS
photo: © Marko Prezelj, production: SIDARTA
BRINOX d.o.o.
Sora 21,
SI–1215 Medvode
Slovenia
tel +386 1 361 97 30
fax +386 1 361 97 20
[email protected]
www.brinox.eu
PH201505–EN
PERSONALIZED SOLUTIONS