Water is undeniably one of the most critical resources for the pharmaceutical industry. It encompasses a myriad of applications ranging from solution preparation, material processing to facilitating cleaning validation of the process equipment.
There are different grades of water depending upon the application in pharmaceutical manufacturing. However, it is similar to the criticality of the process upon which different classes of cleanroom are based.
Essentially based on the application, the types of water can be categorized as follows:
- Potable Water– Used for drinking, gardening & domestic applications.
- Soft Water– Used for process equipment cleaning & in boiler for black steam generation.
- Purified water (PW)- Used as an excipient of non-parenteral products.
- Water for Injection (WFI)- Used as an excipient of parenteral products.
Raw water supply to a pharma manufacturing facility could be carried out from one of the sources, viz. municipal supply, groundwater, bore well, etc. However, numerous impurities often get filled in the said sources of raw water, thereby demanding removal and right treatment before the water is ready to be taken into final utilization. These impurities can be in the form of Suspended Solids, Colloidal Impurity, Microbial Impurity, Dissolved Impurity, Metallic Impurity, Gaseous Impurities or Organic Impurities. Therefore, a pharmaceutical water purification system undergoes minute, distinct processes to ensure that all impurities are thoroughly removed.
Thus, the path forward begins with Raw Water Analysis; a report on the same is attached below:
|Sr No.||Description||Unit||Ref Protocol|
(only for information)
|2||Appearance after Filtration (0.45 microns membrane)|
|3||Colour (Hazen Units)||Hazen||IS:3025 PT-4-2002|
|5||PH @ 25 degree C||IS:3025PT-11-2002|
|6||Electrical Conductivity at 25ºC ms/cm||us/cm|
|7||Total Dissolved Solids||mg/lit||IS:3025PT-16-2002|
|8||Silt Density Index (SDI)|
|9||Copper as Cu||mg/lit||ALPH 21st Ed.,3111|
|11||Fluoride as F||mg/lit||ALPH 21st Ed.,4500-F|
|13||Manganese (as Mn)||mg/lit||ALPH 21st Ed.,3111|
|14||Turbidity in NTU||NTU||IS:3025 Pt-10-2002|
|15||Total Hardness as CaCo3 – ppm||mg/lit||IS:3025 Pt-21-2002|
|16||Carbonate Hardness as CaCo3 – ppm||mg/lit|
|17||Nitrate (as NO3)||mg/lit||IS:3025 Pt-34-2003|
|18||Nitrate as CaCO3||mg/lit|
|20||Non-Carbonate Hardness as CaCO3||mg/lit|
|21||Phenolphthalein Alkalinity (as CaCO3)||mg/lit||IS:3025 Pt-23-2003|
|22||Methyl Orange Alkalinity (as CaCO3)||mg/lit||IS:3025 Pt-23-2003|
|23||Alkalinity (as HCO3 -)||mg/lit|
|24||Phosphate, phosphor, PO4 –||mg/lit|
|25||Sodium as Na||mg/lit|
|26||Calcium as CaCO3||mg/lit|
|27||Magnesium as CaCO3||mg/lit|
|28||Chlorides as CI||mg/lit||IS:3025 Pt-32-2003|
|29||Sulphate as SO4||mg/lit||IS:3025 Pt-24-2003|
|30||Iron as Fe||mg/lit||ALPH 21st Ed.,3111|
|31||Total Suspended Solid (T.S.S.)||mg/lit|
|32||Reactive Silica as Si||mg/lit|
|33||Colloidal Silica as Si||mg/lit|
|34||Microbial Count: Total Viable Aerobic Count||CFU/ML|
The classification mentioned below will help us get a more holistic view of the pharmaceutical water purification systems:
1) Pre-treatment Systems
a) Chlorination – This is the primary step of water purification system that involves Chlorination (NaOCl) Dosing System. Chlorine being a strong oxidant, rapidly kills harmful viruses and bacteria.
b) Filtration- Filtration is the most traditional method where water purification is undertaken through filter media. The media selected is based on the raw water parameters where the raw water analysis plays a vital role. These are also known as Sand Filters and are largely employed to get rid of Total Suspended Solids (TSS) named Multi Grade Filter (MGF). The water at the outlet of MGF is Potable Water.
c) De-chlorination – At the beginning of the purification system, the oxidation properties of chlorine play a significant role in the removal of viruses and bacteria. However, as the purification system proceeds, the same oxidation properties pose a great threat to certain critical components like the RO membrane or the piping. The presence of free chlorine can often put these components at the risk of scaling and salt precipitation.
De-chlorination can be done by the following 2 methods:
c.1) Activated Carbon Filter
c.2) SMBS (Sodium Meta Bi Sulphate) Dosing System
d) Softening- In this method, the introduction of softener has a good effect on the ion exchange principle as it replaces calcium and magnesium ions (hard water) with Sodium Chloride Ions NaCl (Soft Water). Hence, the water available after softening is termed Soft Water.
e) Ultra-filtration (UF)- UF is carried out by forcing water through a hollow fiber membrane which helps in reducing the Silt Density Index (SDI) of water. SDI also contributes to increasing the RO unit’s efficiency by eliminating the possibility of choking the RO membrane.
f) Dosing System- Dosing system is the addition of external agents in water to achieve certain objectives. The three types of this system are hereunder:
f.1) Anti-scalent Dosing- This is done to prevent the tendency of scaling of RO membrane due to the high silica content in raw water.
f.2) pH Correction Dosing – Elimination of carbon dioxide before the softening process can harm the efficiency of this process. Correction of the pH level of water ensures that all its important properties remain intact.
f.3) SMBS Dosing- SMBS Dosing is carried out with Sodium Meta Bi-Sulphate, which removes the presence of chlorine in feed water. It helps achieve de-chlorination of water and increase the life of RO membranes.
2) Post-treatment System
a) Reverse Osmosis (RO)- RO is a water purification process that forces water through a partially permeable membrane. This process involves a high-pressure pump which increases the pressure on water to pass through the membrane. As a result, the water gets divided into ‘permeate’ and ‘reject’. While the former has low salt dissolved content, the latter comprises high salt dissolved content. Based on the applications, the RO systems employed can be of 2 types: –
a.1) Hot Water Sanitization (HSRO)
a.2) Chemical Sanitization (CSRO)
b) Electro-deionization (EDI)- As the name suggests, EDI works on the principle of ion exchange. The construction of an EDI is very simple; it consists of 2 membranes, namely, the cathode and the anode. The primary difference between the 2 electrodes is that while cations get attracted towards the cathode, the anions get attracted towards the anode. This principle essentially leaves the water free on ions (deionized water).
c) Ultraviolet Disinfection (UV)- UV light is used to disinfect various algae, molds, viruses and other microorganisms. The UV light destroys the DNA of the microorganisms, thus preventing their further growth. UV is the final step in generating PW, and the output received is termed Pure Water.
3) Water for Injection (WFI)
WFI generation is based on the process of distillation. The PW generated by the purification process is passed through a Multi Column Distillation Plant (MCDP), which works on the principle of heat exchange. The PW undergoes a series of columns subjected to distillation by the repeated heating and cooling process. The output obtained at the end of MCDP is termed as Water for Injection.
Every water purification system is unique, highly customized, and tailored to the raw water parameters, necessary end product parameters, and optimum design capacity. Therefore, the system must be neither over-designed nor under-designed to ensure maximum efficacy.
Talk to our water experts to get the right guidance on the custom-made solutions dedicatedly designed to suit your specific requirements.