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METHODS TO PRODUCE WATER FOR INJECTION (WFI)

IV bags - Intravenous solutions in surgical room.
IV bags in surgical room. Water for Injection is the key component for IV fluids manufacturing.

Water for Injection: two main methods to produce WFI

There are several methods for producing WFI-Water for Injection, with multiple-effect distillation and vapor compression as the two primary methods recognized by the FDA. Both are established methods, offering differing advantages dependent on the proposed application.

BRAM-COR employs these two different technologies with some versions (multiple or single effect distiller, water pretreatment options) to obtain compendial WFI, the worldwide standard for pharmaceutical applications, I.V. Fluids and parenteral solutions.

Vapor Compression Distillation

VC System is also known as thermocompression / vapor recompression or thermal / mechanical vapor compression. It is a technology similar to the evaporation systems used for the water desalination (Vapor compression is also a common term in the refrigeration industry).

Furthermore, the VC system can be powered by either steam or electric heating, and have a minimal feedwater quality requirement due to lower operating temperature. 

VCD units are driven by a more mechanical process than MED, involving a compressor and other moving parts to compress steam and increase its pressure/temperature for evaporation. 

Multiple Effect Distillation

ME System is a well-know method. Multiple-effect stills are mainly noted for their multiple column design which re-uses steam energy through the process, requiring minimal moving parts, but requiring cooling water for final distillation of product.

In case of low required capacities (since MED systems absorbing much energy and cooling water) you can also get WFI from Single Effect Distiller (BRAM-COR Mod. DPSG), that is  both a Still and a Pure Steam Generator.

The third method to produce WFI: Reverse Osmosis + Ultrafiltration (UF)

We do not think that RO system is the safest method to produce Water for Injection (WFI), unless the feed water is really excellent. Above all, theoretically, with the availability of more technologically advanced membranes, we can produce cold WFI with the addition of ultrafiltration (Techniques such as water softening, descaling, pre filtration, degasification, nanofiltration, electro-deionisation, ozonation, UV treatment and micro-filtration should all be considered, in relation to the feed water quality). So, we can produce cold WFI that meets all the parameters required (USP, EP, JP, …).

Therefore, for Bram-Cor is not a problem the design of a turnkey plant producing WFI from reverse osmosis. However, once in production, the RO system requires -unlike distillers- a continuous control on its efficiency, in terms of membrane degradation, biofilm prevention  and microbial charges, with periodic sanitization and validation. If there are no obstacles in ensuring this constant monitoring, which must also concern distribution loops, the reverse osmosis system can offer a real advantage, reducing the energy demand.

 

Producing Water for Injection from Vapor Compression distillation

The advantage of a higher efficiency (low cost by quantity produced in comparison to MED)

BRAM-COR Vapor Compression Distiller Mod. STMC, improperly called thermocompressor or thermal recompression still, produces Water for Injection, the reliable compendial distilled water for pharmaceutical applications.

As a result, many products benefit from WFI, such as LVP or SVP (Large volume / Small Volume Parenteral), any injectable product as well as washing medias and special solutions where

  • quality factors (such as the sterility, elimination of the pyrogens and of the chlorine solvents with low molecular weight)
  • economical factors (low running costs)

are critical for the success of the pharmaceutical process.

The STMC distiller can produce both cold Distillate or hot Distillate with huge savings of energy costs and with no need of cooling water. STMC vapor compression distillers operate with electrical heating (STMC EL) or plant steam heating (STMC ST) or even through both electrical and steam heating systems (STMC ES). Capacities range: from 20 to 20.000 lph with one/more blowers.

Bram-Cor - STMC ST 330 T
Methods of producing WFI: the front view of a classic BRAM-COR STMC Vapor Compression Distiller.
The recognized benefits of the Vapor Compression Technology
  • Low energy consumption
  • No need of cooling water to condensate the pure steam
  • No need for high quality inlet water (in some cases even softened water can feed the VC still)
  • Very high quality of the WFI thanks to the strong degassying process
  • No need to pressurize the inlet water
  • WFI outflow at high pressure (1 – 1.5 bar) without any additional pump
  • Extremely safe process, with no risk of any cross contamination through plant steam or inlet water
  • Highest flexibility in terms of capacities and WFI temperatures
  • Reduced Maintenance

The design, construction and documentation of the STMC distiller strictly complies with GMP and FDA regulations, ensuring an easy certification by the relevant authorities. In detail:

  • The Distiller is made in certified AISI 316L stainless steel
  • Any internal part in contact with the infeed water, the Pure Steam and the Distillate is mirror-polished
  • All hydraulic connections are sanitary tri-clamp or flange connection
  • Any  gasket is made in PTFE / EPDM
  • All weldings are T.I.G
  • Vapor is compressed by a special blower.
Note about blower

a further enhancement of VCD has been the BRAM-COR multistage blower compressor which runs under 4000 rpm, significantly reducing operating noise level (below 65-70 dB) and maintenance.

A standardized approach to mechanical seal design can also reduce the maintenance time typically associated with their changeover as well as prevent or minimize leakage over a longer operating period. The issue of non-condensable gas removal is as standard addressed by vapor compression designs by preceding the compressor with a deaerator.

Note about evaporation

A vertically-mounted compressor will evaporate water on either a falling film or thin rising film principle for drier steam, whereas spray film units direct water over the horizontal surface area of the evaporation tubes for a more wetted surface.

Since the separation of impurities from the steam is done by more of mechanical process (vs. multi-effect’s centrifugal action) a secondary separation system is in place. Commonly, a demister pad is used but a newer approach utilizes a baffle similar to those found in multiple-effect stills for a design which is considered more sterile as it is fully drainable.

Therefore, 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 according to 21 CFR PART 11.

See also: vapor-compression-distiller.com

 

Producing Water for Injection from Multiple Effect distillation

The advantage of less moving parts (with lower maintenance requirement)

BRAM-COR Multiple Effect Distillers Mod. SMPT are designed and manufactured according to cGMP to produce compendial Water for Injection. Each unit contains a number of boiling columns (or effects) with the first column producing pure steam, which is condensed and re-distilled in the following columns decreasing the operational costs.

Heating for evaporation and cooling for condensation processes are performed by double tube sheet (DTS) exchangers. Condensation is achieved by means of the thin-falling film technology. The process is repeated in each column: the higher the quantity of columns  the lower overall the consumption of the equipment. The quantity of columns therefore does not influence the quality nor the output of the equipment.

Bram-Cor SMPT ST5 multiple effect distiller
Methods of producing WFI: a classic SMPT Multiple Effect Distiller

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. The first column of the Still may be used to produce also Clean Steam alternatively or even at same time. Pressure vessels are designed according to ASME and PED regulation 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 Teflon membranes and AISI 316 L SS polished body
  • ASTM C-795 – compliant insulation.

Capacities range: from 50 to 15.000 lph with three to ten columns.

Multiple Effect Distiller Operating system

Note about preheaters and evaporators

Preheaters will make the Multiple Effect still operate more efficiently in regards to steam and water consumption, but are not always a standard feature. A preheater can be installed prior to the first column for additional benefit, or prior to all columns for maximum benefit. Evaporators will be located internal or external to the column.

The evaporators bear the brunt of varying pressures and temperatures. If there is any severe failure to the still, it will most likely be with the evaporator. For this reason, the first evaporator should have a double-tube sheet design; it should be decided in the specification process if all evaporators should be of double tube-sheet design since this is not a standard with all manufacturers.

See also: www.multiple-effect-water-distiller.com

Producing Water for Injection from Single Effect distillation

BRAM-COR Single Effect Distiller Mod. DPSG is  both a Still and a Pure Steam Generator. The production process consists in PW water evaporation followed by pure steam separation and condensation. The steam is purified using centrifugal and gravity separation methods. This equipment produces dry, saturated steam to be used as sterilizing agent.

Naturally, the Pure Steam, when condensed through a Double Tube Sheet condenser, 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.

BRAM-COR Single Effect Distiller
Methods of producing WFI – Water for Injection: a classic DPSG Single Effect Distiller

BRAM-COR CPSG, Pure Steam Generator, produces dry and saturated steam: this steam, when condensed, meets USP requirements for Water for Injection (WFI) (see the relevant page on this site; see also puresteamgenerators.net).