PhEn 601

Water Purification Process for a Parenteral Drug

Process

In order create a water that is used for a parenteral drug, the water must be highly purified and also
sterile. The water must be at the standards of that of water for injection (WFI). For the process, the feed
water will come from a municipal source, i.e. tap water. This will reduce pretreatment process
operations. The feed water will then be fed through a large filter. This will be to ensure any large
contaminants are removed. The next step in the process will be will be to run the water through a water
softener (ion exchanger) to remove metal ions such as Ca++ and Mg++. After the water softener, the
water will run through a vessel containing activated carbon. This will be to adsorb any Cl- in the water.
Next the water will pass through a fine screen to remove any small particulates and activated carbon
that may have been picked up in the previous step. The softener and activated carbon steps are
necessary to ensure any contaminants are removed that may compromise the next step of the process,
reverse osmosis. The water will then enter a pump to ensure a high enough pressure to pass through
the reverse osmosis membrane process. The water will then proceed to the reverse osmosis process
with a membrane made of a thin film composite. This is to ensure a maximum rejection of particulates
and a long life time of the membrane. After this the water will pool in a reservoir tank that has a recycle
line with the final step in the process. The recycle is to prevent stagnation of the water that would
promote biological growth. After the storage tank the water will go into the polishing process. The
polishing process consists of a vessel containing a mixed bed of cation and anion resin beads. The beads
capture and remove any ions that exist in the water. Next the water will pass through a tank where it is
exposed to a large amount of ultra violet radiation to ensure all microorganisms are killed. In order to
remove the dead microorganisms, the water is passed through a filter with a screen size of 200 nm.
After this the water reaches its last step, the distillation process. This will ensure all contaminants and
pyrogens are removed or destroyed. From here the water will be sent to its destination with the
attached recycle stream to the storage tank.

Technologies

Water Softeners – Water softeners or ion exchangers work by exchanging heavier alkali earth metals for
alkali metals. This done via a resin bead medium. The resin beads are saturated with Sodium, an alkali
metal, and are exchanged with heavier alkali earth metals such as Ca++ and Mg++. The process is effective
but the beads when saturated with the alkali earth metals must be flushed out with a brine to
resaturate the beads with Na+.

Reverse Osmosis – The reverse osmosis process is purely dependent on diffusion. Reverse osmosis relies
on a concentration gradient of the incoming fluid and an external fluid that is separated by a permeable
membrane that allows for the passage of ions but not fluids. This allows contaminants to pass into the
waste fluid and out of the “working” fluid. This creates a highly pure fluid.

Deionization – For the mixed bed process, a tank filled with polymer resin beads that have affinities for
positive and negative charged ions. The water is then passed across these beads and the charged ions
are captured by the beads. To replenish the beads, a co-current flow of acid and base are passed
through the beads to release the attached ions.

UV Radiation – Ultra violet radiation is to ensure that all microorganisms are destroyed and not left in
the final product.

Distillation – The distillation process is one in which the fluid is heated to its boiling point and it is
evaporated, later to be condensed. The cooling process is done by passing the evaporated gas through a
chamber with a cooling fluid on an outer shell. This method is in general costlier due to the requirement
of the fluid needing to be heated to its boiling point. This is particularly true with considering its large
heat capacity.

Regulatory Requirements

For water for injection in the pharmaceutical industry it is required that the final water falls under
certain regulation. This regulation requires that the water has:

Conductivity measurements are at standards

Total Organic Carbon ≤ 500 PPB

10𝐶𝑃𝑈
Microorganisms ≤ 100𝑚𝐿
0.25𝐸𝑈
Endotoxin ≤
𝑚𝐿

Where PPB is parts per billion, CPU is a colony forming unit, and EU is an endotoxin unit

Materials

All materials will be made of 316 L stainless steel. This will be to ensure that there is no contamination
of the final product or contamination throughout the process. This material is also selected to ensure
that at all times pH, chemicals, and temperature will not compromise the final material of construction.
All joints will be fused together with orbital welding to ensure smooth joining and no threaded pieces
that would promote contamination.

Equipment

Water Softener – WS961

Activated Carbon – Carbon Activated Corporation: Coconut Shell activated carbon with particle size of
0.250 to 0.075mm.2

Reverse Osmosis – PRO1P89-16-3x2 from MECO3

Storage Tank – MECO4

Mixed Bed Ion Exchanger – Lenntech5

UV System – SHF 180 from ESP Water Products6

Distillation – 8ME300 form MECO7

References

1) https://www.meco.com/product/biopharmaceutical-water-softener/
2) https://activatedcarbon.com/products/coconut-shell-activated-carbon/
3) https://www.meco.com/product/biopharmaceutical-reverse-osmosis/
4) https://www.meco.com/product/biopharmaceutical-storage-distribution/
5) https://www.lenntech.com/applications/ultrapure/mixed/mixed_bed_plants.htm
6) https://www.espwaterproducts.com/viqua-shf-180-model-183-gpm-commercial-uv-system-shf-
180
7) https://www.meco.com/product/biopharmaceuticals-multiple-effect-stills/