WATER

TREATMENT
SYSTEMS
PURIFIED
WATER
WATER FOR
INJECTION
PURE STEAM
 BRAM-COR
WATER TREATMENT
LINES
BRAM-COR Pharmaceutical Water Treatment Systems are designed to produce
compendial:
- PW PURIFIED WATER
- HPW HIGHLY PURIFIED WATER
- WFI WATER FOR INJECTION
- PS PURE STEAM
Pre-treatment options, monitoring of critical parameters, regulatory requirement
for product quality, consumptions, microbiological control, operation and mainte-
nance requirements, lifecycle costs are taken into considerations in the design of
all processing steps, from feed water to the point of use.
Special care is given to the choice of sanitary materials. Product-contact surfaces
are in certified AISI 316L stainless steel, with standard roughness ≤ 0.4 µm.
PTFE gaskets ensure perfect sealing. Advanced Process Analytical Technologies
are applied for monitoring issues and professional GAMP compliant automation is
provided for system control.

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 PRTW Water Pre-treatment System 4

CROS Reverse Osmosis Systems 5

STMC Vapor Compression Distillers 6

SMPT Multiple Effect Distillers 7

CPSG Pure Steam Generators 8

DPSG Single Effect Distillers 9

LOOP Distribution Systems 10

SCADA Control Systems 11

SCAM Heat/Cool Exchangers 12

STOC Storage Tanks 13

KOMB WFI + PS Generators 14

GENO Ozone Generators 15

STDA Standard Accessories & Components 15

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 MMF 4600 ADUF 4600 PRT 8000

PRTW WATER PRE-TREATMENT SYSTEMS

BRAM-COR Water Pre-Treatment Systems are customized upon a thoroughful evaluation of feed-
water quality using the customer’s water analysis. Raw water can be pre-treated to remove con-
taminants (such as particulates, calcium and magnesium salts, heavy metals, organics and bacteria)
through different steps, including:
- UV lamps
- Ozone units
- Cartridge microfiltration
- Ultrafiltration units
- Multimedia filters
- Automatic duplex softeners
- Industrial RO
Chemical dosing stations are added for water disinfection and/or chlorine neutralization. Pretreated
water quality is constantly monitored to ensure suitability to feed downstream water treatment equip-
ments, such as RO units or distillers.
Standard versions are designed for
CIP sanitization. Upon request, for
an effective microbial control strat-
egy to prevent biofilm formation,
most pre-treatment systems can
be supplied in hot water sanitizable
version.

CAPACITIES RANGE
From 100 to 20,000 lph

4
ADD HWS 2000 ADD HWS
 CROS SINP EDI 1000

CROS REVERSE OSMOSIS SYSTEMS

CROS Reverse Osmosis Systems are designed to produce compendial purified and higly purified
water through several water treatment steps, according to feed water quality and production
needs. Water treatment steps, which are necessary to separate the water from organic substances,
high and medium molecular weight ions, and from some bacteria and pyrogenes, may include:

- Sodium hypochloride dosing station

for water disinfection and oxidation
of organic substances,
reducing the bacterial charge
- Sodium metabisulphite dosing
station for neutralization of calcium
carbonate and chlorine
- 25 µm + 5 µm filtration system
to eliminate solid substances
in inlet water
- Single or double osmotic stages
- Electrodeionizator
- UV lamp
CROS EDI 500 CROS SINP 20000
CAPACITIES RANGE
From 100 to 20,000 lph

purified water generation

Purified water is usually obtained through single stage RO + Electrodeionization, double stage RO
and double stage RO + EDI. In each RO stage, water is processed through thin film composite RO
membranes, offering the highest rejection of contaminants. Two different flows are generated by
the RO system: permeate water, corresponding to PW specification, and RO concentrate, which is
recycled in the system in order to obtain a higher recovery with a lower consumption of inlet water.
CROS equipments, with a range of capacity spanning from 100 up to 20,000 lph, are manufactured
according to all cGMP and FDA rules, including:
VESSELS DETAIL
- Centrifugal booster pump in
AISI 316L stainless steel,
completely mirror polished both
internally and externally
- AISI 316L stainless steel membrane vessels
- Sanitary in-line instrumentation
to monitor product critical parameters,
such as conductivity and temperature
- Full automation managed through
GAMP-compliant hardware and software
- Framework and control board in AISI 304
stainless steel satin finished
- CIP sanitization or HOT WATER
5 sanitization.
 STMC ST 330 STMC ST 880

STMC VAPOR COMPRESSION DISTILLERS

BRAM-COR STMC Vapor Compression Distillers produce compendial distilled water for pharmaceu-
tical applications, such as I.V. solutions, injectables, washing systems and special solutions where
both quality factors, such as the sterility, elimination of the pyrogens and of the chlorine solvents
with low molecular weight,
and economical factors, as
well as the low production
costs, are critical for the suc-
cess of the pharmaceutical
process.
STMC vapor compression dis-
tillers can operate:
- With electrical heating
- With steam heating
- Both with electrical
and steam heating systems

CAPACITIES RANGE
From 20 to 12,000 lph, with
single or double compressor

wfi at extra low management cost

The STMC distiller can produce both cold distillate at a temperature
and hot distillate with huge savings of energy costs and with no need
of cooling water.
The design, construction and documentation of STMC distiller strict-
ly complies with cGMP and FDA regulations, ensuring an easy certi-
fication by the relevant authorities. In detail:
- The distiller is made in certified AISI 316L stainless steel
- All internal parts in contact with the infeed water, the Pure Steam
and the Distillate, are mirror-polished
- AISI 304 frame, jackets and control board
- All hydraulic connections are sanitary tri-clamp
or flange connection STMC EL 60
- All gaskets are made in PTFE
- All weldings are T.I.G. (Tungsten Inert Gas)

Vapor is compressed by the special blower. A full

automation ensures easy operation and total
monitoring of critical parameters, by means of
certified in-line instruments and of a careful
alarm policy.
Access policy and records can be managed ac-
cording to 21 CFR PART 11.
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STMC ST 3000
 SMPT ST3 150

SMPT ST6 1300

SMTP MULTIPLE EFFECT DISTILLERS

BRAM-COR Multiple Effect Distillers are designed and manufactured according to cGMP to pro-
duce compendial Water for Injection. Each unit contains a number of boiling columns (or effects),
with the first column producing Pure Steam, which is either condensed in the following columns
decreasing the operational costs, or used as PS.

CAPACITIES
RANGE
From 50 to 15,000 lph,
with three-eight columns
configurations

wfi from multiple distillation

Heathing for evaporation and cooling for condensa-
tion processes are performed by double tube sheet
heath and cool exchangers. Condensation is achieved
by means of the thin-falling film system. The process
is repeated in each column; the higher the number,
the lower the consumption of the equipment.
A special labyrinth-separator installed at the top of
each column separates the steam generated by the
evaporation process from entrained substance in the
steam itself. The result is a pure, “dry”, pyrogen-free
steam, condensed in compendial Water for Injection.
Pressure vessels are designed according to PED regu-
lation, and the equipment features:

- Double tube sheet heath exchangers

- Certified AISI 316L stainless steel mirror-polished
and passivated product contact surfaces
- AISI 304 frame, jackets and control board
- PTFE gaskets
- Pneumatic valves with PTFE membranes
and AISI 316 L SS electro-polished body
- ASTM C-795-compliant insulation
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SMPT ST8 3000
 CPSG ST 150

CPSG ST 2500

CPSG PURE STEAM GENERATORS

Our CPSG Pure Steam Generators produce dry, saturated steam, suitable for
sterilization of pharmaceutical production plants, for direct contact with active
pharmaceutical ingredients, for parenteral and non-parenteral dosage form
applications. The steam, when condensed, meets USP requirements for Wa-
ter for Injection. The steam is purified using centrifugal and gravity separation
methods.

CAPACITIES RANGE
From 20 to 5,000 Kg/h

pharmaceutical pure steam

cGMP and PED standards are baseline criteria in our CPSG Pure Steam Gen-
erators design and construction: material and instruments are certificated and
all welds are made by qualified welders. In detail:

- The evaporation column is designed to minimize steam speed to avoid

the entrainment of water droplets, which are separated from the steam by
KPSG ST 4500 means of a special separator.
- A Double Tube Sheet Heath Exchanger provides heat-
ing of pre-treated feed water above the boiling tem-
perature, generating Pure Steam which expands into
the evaporation column. Heathing medium in the DTS
Heath Exchanger is typically industrial steam at 100 to
120 psig (7.9 to 2.0 bars).
- Pure Steam pressure is maintained by an electronic
control system, modulating the supply steam control
valve and monitoring the evaporator feed water.
The system shall be fed with Purified Water.

KPSG Kettle Pure Steam Generators provided with a

horizontal evaporation chamber with kettle end, are
also available for special space needs.
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 DPSG ST 500

DPSG EL 50

DPSG SINGLE EFFECT DISTILLERS

PS & WFI from a single effect distiller:
each DPSG equipment is both a Sin-
gle Effect Distiller and a Pure Steam
Generator. This equipment produces
dry, saturated steam to be used as
sterilizing agent.
The Pure Steam, when condensed
through a double tube sheet con-
denser, meets the requirements of
international pharmacopoeias for
Water for Injection. The system can
therefore provide a simultaneous
production of Pure Steam and Water
for Injection. The production process
consists in PW water evaporation fol-
lowed by Pure Steam separation and
condensation.
The steam is purified using centrifugal and gravity separation methods. The equip-
ment is made in AISI 316L stainless steel for all parts in contact with the process
fluid and steam, and it is designed according to European PED pressure regulation.
All pipes are orbital welded when
possible, with inert gas protection.
Moreover:

- Active surfaces are passivated.

- The parts in contact with the pure
steam are polished (Ra ≤ 0.4 µm)
- The Skid is in stainless
steel AISI 304 satin finished
- The Control Cabinet is in stainless
steel AISI 304 satin finished
DPSG equipments are available in elec-
trically or steam heated versions.
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LOOP DISTRIBUTION SYSTEMS
BRAM-COR integrates its PW-WFI-PS Generation Equipment with state-of-the-art distribution
loops. Loop design is the result of a careful evaluation of Points of Use delivery criteria such as:

- Maximum istantaneous flow rate

- Pressure & temperature
requirements
- Sanitization issues
- Periodic consumption
requirements and duration
- Method of delivery
(automatic or manual)

Loop construction is carried out by qualified welders following BRAM-COR sanitary piping pro-
cedures, according to ASME standards. All pipelines are passivated and inspected, according to
ASME/BPE acceptance criteria, to check quality of welds, effective passivation, hydrostatic tight-
ness, full drainability, absence of dead-legs, fluid dynamics.

A thoroughful loop documentation, including iso-

metric drawings, welding reports, boroscopy records,
passivation certificate and test reports is provided to
complete the supply.

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 SCADA CONTROL SYSTEMS
BRAM-COR GAMP-Compliant Automation: from equipment control to production line supervi-
sion, SCADA Systems provide full management control throughout the plant lifecycle. Data man-
agement includes: trends and electronic records, electronic signatures and alarms management,
audit trails, lifecycle check counts, display of manuals & documentation.

gamp-compliant automation
The software is usually configured on WinCC Flexible platform. Other platforms may be used upon
request, as A/B Rockwell. Secure access policy, according to 21 CFR PART 11, includes three differ-
ent access levels. Each authorized user shall log-in by digiting user ID + password, the combination
of which is unique and may be changed by the Customer in runtime. BRAM-COR control systems
are configured to store and show live-data for one year. Different
needs shall be highlighted by the Customer and involve HD of bigger
size for a different configuration of WinCC Flexible program.

All historical data can be exported and saved by the Customer for
long lasting backup. All parameters modified by the customer are
stored and limited, all parameters and I/O (analogic and digital)
of the system can be printed on the report, allowing a quicker as-
sistance, in accordance to 21 CFR PART 11. Start/stop of operating
modes are recorded on the audit trail. Audit trail file can be exported
by the Customer on a USB key or Ethernet.

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 HEAT AND COOL EXCHANGERS

SCAM HEAT/COOL EXCHANGERS

A heat/cool exchanger is due to heat up, cool down or keep process water temperature to the
desired values, by heat transfer between two fluid media. For efficiency, BRAM-COR Double Tube
Sheet Heat/Cool Exchangers are designed to maximize the surface area of the wall between the
two fluids, while minimizing resistance to fluid flow through the exchanger.
Tube diameters, thickness, length and number are calculated to withstand internal tube pressure
and shell overpressure in accordance to space and performance requirements.

In pharmaceutical processes, BRAM-COR SCAM

DTS exchangers are typically used for high pres-
sure application, for hot water sterilization of
loops and tanks, for water cooling/heating user
points. All product contact surfaces are built in
AISI 316 L stainless steel, internally mirror pol-
ished, Ra ≤ 0,4 μm.
The exchangers are insulated and clad with 304
SS satin finished. Tube ends are manually ex-
panded to fit in the tube sheet. All materials are
fully traceable. Non-destructive tests are carried
out by skilled personnel to ensure compliance
to cGMP and Pressure Equipment Directive.

SCAM DTS may be embedded in the equip-

ment (ex. in SMPT distiller) or on self-standing
skid, and fitted with sanitary valves and pumps,
steam trap, temperature probe.

SCAM DTS 172-2 SCAM DTS 06420

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 STOC STORAGE TANKS
BRAM-COR STOC Storage line includes a complete range of pharmaceutical hold-
ing tanks for storing compendial or non-compendial water.

high quality pharmaceutical vessels

Material and components traceability and certification are assured in all BRAM-COR vessels. Rigor-
ous sanitary piping welding and inspection procedures, ND testing procedures in compliance to in-
ternational standards for pharmaceutical equipment are enforced in our workshop. Basic features
of our fully cleanable storage tanks:

- Certified AISI 316L stainless steel mirror-polished (Ra ≤ 0,4 μm)

product contact surfaces and components
- “Tank in tank” insulation bottom and wall
- Vertical or Horizontal design
- Customized heath and cool jackets, cladded in satin finish
AISI 304 stainless steel
- Manhole

The capacities range from 100 up to 25.000 litres, while sizes and shapes are
scaled up according to specific URS, in order to fit different space require-
ments including for instance:

- Any instrumentation / control / management system

- Heating and cooling systems
- Platforms and stairs
- PED certification upon request
All tanks can be integrated with
BRAM-COR SCADA computer-
ized control system, managing
PW or WFI generators, loop
and user points, which also
records and produces the files
and documents necessary for
the international pharmaceuti-
cal validation.

STOC WSIE 2000 HORIZONTAL STOC PSIA 1500

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 KOMBO WFI 250 + PS 400

KOMB COMBINED WFI + PS GENERATORS

BRAM-COR KOMBO is a unique equipment for the simultaneous production of WFI and PS, com-
bining the double functions of a multiple effect distiller and of a Pure Steam generator on a single
skid, shrinking space needs.
A central SCADA controls the two units, providing separate or concurrent outlet of Water for Injec-
tion or/and Pure Steam.

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 GENO

GENO OZONE
GENERATORS
Thanks to its high oxidation potential, ozone is
proven to be one of the most effective and safe
methods to remove antibacterial, anti-viral, and
anti-fungal activity.

sterilizing pw loops
pw storage tanks
BRAM-COR full-stainless steel GENO Ozone
Generators are conceived for pharmaceutical
application, i.e. for water disinfection and loop
sanitization.
Ozone quantity during and after sanitization
is constantly monitored by ozone analyzers,
while residual ozone in water is automatically
destroyed by a sanitary UV lamp before the use
in the process.
Sanitary piping, valves, pumps and instruments
complete each GENO unit.

STDA STANDARD ACCESSORIES AND COMPONENTS

UV LAMP DETAIL

Special sanitary components in AISI 316L are

manufactured by BRAM-COR to fit our water
treatment systems, such as:
- 316L SS housings for water filters
- 316L SS housings for air filters
- UV Lamps & Controls

15 WATER FILTER AIR FILTER

BRAM-COR KEY DESIGN CONCEPTS

05 2012
A full understanding of the drug production process is the key concept for correct design. BRAM-
COR engineering focuses on fluid drugs sterile production processes, such as parenteral solutions,
oral solutions, ophtalmic solutions. The definition, assessment and monitoring of critical param-
eters directly affecting product quality are the baseline for the application of suitable Process Ana-
lytical Technologies for in-line and at-line quality control. BRAM-COR work breakdown structure
consists in following main activities:

- Design
- Construction (mechanical, electro-pneumatic, SW configuration)
- Testing
- Documentation
- Installation
- Validation
- Assistance

Every process follows rigorous cGMP-compliant Standard Operative Procedures. Specification, con-
struction, and verification steps within the lifecycle are carried out according to GAMP “V-model”,
considering risk assessment, architecture of system components, functional specification, sanitiza-
tion and validation issues with special overview to a sustainable maintenance of the system.

WORLDWIDE SERVICES
We are currently delivering our machines and building complete water treatment systems and
preparation lines all over the world. Top quality GMP equipment must necessarily be integrated
through a proper high level of professional services including: Technical Documentation, Factory
Acceptance Test, Installation, Commissioning, Site Acceptance Test & Start-up, Training, Valida-
tion, After Sales Service. Our worldwide network of skilled agents and our affiliated companies
ensure assistance to our Clients in over 50 countries, from the very beginning of a pharmaceutical
project throughout decades after start-up. Our After Sales Dept. grants punctual and quick deliver-
ies of spares and ongoing technical support.

BRAM-COR S.P.A - V. MERCALLI 12/A - 43122 PARMA - ITALY - TEL +39 0521 538711 - FAX +39 0521 538770
[email protected] - www.bram-cor.com - P.IVA 01699350342