1. Water Systems in Pharmaceutical Processing

2. Water for Biopharmaceutical processing
Water : One of the most important raw materials :
 used as a basic ingredient
- Cell culture media, buffers, solvent in extraction and
purification, solvent in preparation of liquid form and
freeze-dried products
- used for ancillary processes : cleaning
- ~ 30,000 liters of water:
- in production of 1 kg of a recombinant biopharmaceutical produced in a microbial system
 Generation of water of suitable purity:
- Is central to successful operation of any facility

3. Water for Biopharmaceutical processing 2
Utility water is insufficient because it contains:
Salts, organic matter, particles, and microorganisms that pollute or even destroy products and processes.
Water for the pharmaceutical industry must be of high quality and at the same time meet the regulatory requirements of the pharmacopeia governing the water treatment equipment.
Softened and de-mineralized water is used in many processes to ensure uniform water quality of the end product and to facilitate the final validation.

4. Purified water Prepared from potable water source
Meet pharmacopoeia specification for chemical and microbial purity
Protected from recontamination
Protected from microbial proliferation

5. Purified Water cont. Two levels of water quality :
Purified water and WFI
- Outlined in international pharmacopeias
Use of purified water:
Solvent in the manufacture of aqueous-based oral products
- e.g., cough mixtures
Primary cleaning of some process equipment/clean room floors
Generation of steam in the facilities, autoclaves
Cell culture media
Water for injection (WFI)
Highest purity
Extensive use in biopharmaceutical manufacturing

6. Potable water Water that has been
boiled, filtered, cleaned, or treated
to meet the standards for drinking water
meaning that it is reasonably clear of
contaminants and harmful bacteria.
Thereby, making the water safe
for drinking and cooking.

7. Non-Potable water Non-potable water is raw water from
ground wells
springs,
rivers or lakes
that is not treated at all
It is not safe to drink non-potable water as it could contain unknown contaminants.
Non-potable water may taste normal
but it can carry health risks

8. Generation of Purified water and WFI
Generated from potable water
Potential impurities in potable water:
Multi-step purification steps for purified water and WFI:
Monitoring of each step: continuous measurement of the resistivity of the water
Example: Deionization: anion/cation exchangers
Filters to remove microorganisms: 0.22 µm, 0,45 µm
Reverse osmosis (RO) membrane :
Semi-permeable membrane (permeable to the solvent, water, but impermeable to solute, i.e., contaminants)

9. Osmosis
Osmosis is a special case of diffusion in which the molecules are water and the concentration gradient occurs across a semipermeable membrane.
The semipermeable membrane allows the passage of water, but not ions (e.g., Na+, Ca2+, Cl-) or larger molecules (e.g., glucose, urea, bacteria).
Diffusion and osmosis are thermodynamically favorable and will continue until equilibrium is reached.
Osmosis can be slowed, stopped, or even reversed if sufficient pressure is applied to the membrane from the 'concentrated' side of the membrane.

10. Reverse Osmosis Basics
Osmosis is a natural phenomenon that provides water to all animal and vegetable cells to support life
Water moves from a high concentration of water (less sugar/salt dissolved in it) to a low concentration of water (more salt/sugar dissolved in it) across a semi-permeable membrane
This means that water can cross a selectively permeable membrane from a dilute solution (less dissolved in it) to a concentrated solution (more dissolved in it)

11. Reverse Osmosis
Reverse osmosis occurs when the water is moved across the membrane against the concentration gradient, from higher concentration to lower concentration.
To illustrate, imagine a semipermeable membrane with fresh water on one side and a concentrated aqueous solution on the other side.
If normal osmosis takes place, the fresh water will cross the membrane to dilute the concentrated solution.
In reverse osmosis, pressure is exerted on the side with the concentrated solution to force the water molecules across the membrane to the fresh water side.

12. Reverse Osmosis

13. Reverse Osmosis continued.
Reverse Osmosis Membrane:   
The Reverse Osmosis Membrane is the heart of the system.
The most commonly used is a spiral wound
Two options:
the CTA (cellulose tri-acetate), which is chlorine tolerant,
the TFC/TFM (thin film composite/material), not chlorine tolerant.
Post filter (s): After the water leaves the RO storage tank, but
before going to the RO faucet, the product water goes through
the post filter (s).
The post filter(s) is generally carbon (either in granular or carbon block form).
Any remaining tastes and odors are removed from the product water by post filtration.

14. RO Advantages Friendly to the environment,
Do not produce or use any harmful chemicals during the process.
Require a minimal amount of power.
Taste of the purified water is a distinct advantage.
Reverse osmosis removes dissolved minerals and other contaminants that cause water to smell unpleasant, taste poorly and take on unusual colors
Removal of dissolved minerals, metals and other particles benefits plumbing systems.
There is nothing in the water to corrode pipes or collect as sediment

15. Disadvantages
Reverse osmosis treatments require an enormous amount of water.
Such systems typically return as little as 5 to 15 percent of the water pushed through the system, which means it also takes a long time to properly treat the water.
This amount of wastewater can burden home septic systems.
Water entering the reverse osmosis system should also be free of bacteria.
While reverse osmosis systems do remove nearly all microorganisms
the risk of contamination through tiny leaks or deteriorating parts
prevents reverse osmosis systems from being used to remove bacteria

16. Reverse osmosis applications
Sea Water Desalination
Pharmaceutical Water Purification
Bottled Water Production
Waste Water Recycling
Car washes ‘Spot Free’ rinse
Medical Device Manufacturing
Rural Water purification
Brackish Well Water Desalination
Laboratory Water Purification
Food Products and Cosmetic Products
Industrial Water Purification

17. Demineralisation
All natural waters contain, in various concentrations, dissolved salts which dissociate in water to form charged ions.
Positively charged ions are called cations;
Negatively charged ions are called anions.
Ionic impurities can seriously affect the reliability and operating efficiency of a boiler or process system.
Overheating caused by the build-up of scale or deposits formed by these impurities can lead to:
catastrophic tube failures, costly production losses, and unscheduled downtime.
Hardness ions, such as calcium and magnesium, must be removed from the water supply before it can be used as boiler feed water.
For high-pressure boiler feed water systems and many process systems, nearly complete removal of all ions, including carbon dioxide and silica, is required.
Ion exchange systems are used for efficient removal of dissolved ions from water.

18. Water system requirements
Monitoring of water sources
Chemical and microbiological
Endotoxin level (where relevant)
Monitoring of system performance, storage and distribution systems
Records of results, and action taken
Validated sanitization procedure followed on a routine basis

19. Highly Purified Water (HPW)
Prepared from potable water source
Prepared by combination of methods
Reverse osmosis (RO),
Ultrafiltration (UF)
Deionization (DI)

20. Water For Pharmaceutical Use (WPU)
Suitable materials include:
Stainless steel (Low carbon Grade)
Polypropylene (PP)
Polyvinylidenedifluoride (PVDF)
Perfluoroalkoxy (PFA)

21. Bio-contamination control techniques
Periodic sanitization with hot water
Periodic sanitization with super-heated hot water or clean steam
Reliable
Monitoring temperature during cycle
Routine chemical sanitization
Removal of sanitizing agent before use of water important

22. Pipes and Pumps hygienic couplings welded pipes hygienic pumps
hygienic sampling points
acceptable floor
no leaks

23. WPU Documentation to review: Qualification protocols and reports
Water:
Documentation to review:
Qualification protocols and reports
Change control request (where applicable)
Requalification (where applicable)
QC and microbiology laboratory:
SOP for sampling
Procedures and records

24. WPU cont. Sampling There must be a sampling procedure
Sample integrity must be assured
Sampler training
Sample point
Sample size

25. WPU: Water Testing Review method verification Chemical testing
Microbiological testing
Test method
Types of media used
Incubation time and temperature
Objectionable organisms
Must set specifications