A Quick Guide To Pharma Water Systems - Hvax Technologies

26 May.,2025

 

A Quick Guide To Pharma Water Systems - Hvax Technologies

Water is a critical raw material in pharmaceutical and chemical manufacturing operations; consistent and high-quality water supplies are required for a range of operations including production, material processing, and cooling. The various categories of water which need treatments as part of water management are potable water, process water; feed water for utilities, water recycling, and wastewater, water coming from byproduct treatment, water used for odor treatment, water from desalination, and water for irrigation.

Read more

We will restrict this review to pharmaceutical water, wherein it is widely used as a raw material, ingredient, and solvent in the processing, formulation, and manufacture of pharmaceutical products, APIs and intermediates, compendia articles, and analytical reagents.

Process water quality management is of great importance in Pharmaceuticals manufacturing and is also a mandatory requirement for the sterilization of containers or medical devices in other healthcare applications include water for injection. Process waste waters are a term used to define wastewater in any industry coming from the processes occurring in the industry. Process waste waters thus cover any water which at the time of manufacturing or processing comes in contact with the raw materials, products, intermediates, byproducts, or waste products, which are handled in different unit operations or processes.

Different Source of Water:-

  1. Ground Water

The water that is obtained from some deep ground water may have fallen as rain many years ago. Rock and soil and layers naturally filter the ground water to a high degree of clarity and often does not require additional treatment other than adding chlorine or chloramines as secondary disinfectants. Such water may emerge as springs, artesian springs, or may be extracted from boreholes or wells. Deep ground water is generally of very high bacteriological quality (i.e., pathogenic bacteria or the pathogenic protozoa are typically absent), but the water may be rich in dissolved solids, especially with carbonates and sulfates of calcium and magnesium. Depending on the strata through which the water has flowed, other ions may also be present including chloride, and bicarbonate. There may be a requirement to reduce the iron or manganese content of this water to make it acceptable for drinking, cooking, and laundry use.

2. Upland lakes and reservoirs

Typically located in the headwaters of river systems, upland reservoirs are usually sited above any human habitation and may be surrounded by a protective zone to restrict the opportunities of contamination. Bacteria and pathogen levels are usually low, but some bacteria, protozoa or algae will be present. Where uplands are forested or peaty, humic acids can color the water. Many upland sources have low pH which requires adjustment

3. Rivers, canals and low land reservoirs

Low land surface waters will have a significant bacterial load and may also contain algae, suspended solids and a variety of dissolved constituents. Atmospheric water generation is a new technology that can provide high quality drinking water by extracting water from the air by cooling the air and thus condensing water vapor. Rainwater harvesting or fog collection which collects water from the atmosphere can be used especially in areas with significant dry seasons and in areas which experience fog even when there is little rain.

Water report

Below report is just a formal presentation for understanding about the water parameters need to design right water system-

Treated Output Quality of Pharmaceutical water:

pH                               : 5 to 7

Microbial Limit          : < 100 cfu/ml

TOC                             : < 500 ppb

Conductivity @ 25 °C: < 1.3 µS/cm

PHARMA WATER SYSTEM PROCESS FLOW

Based on water sources and parameters and require output quality as per FDA following processes are the widely used in especially in pharmaceutical industries-

PRE-TREATMENT SYSTEM

  1. Chlorination

The most common disinfection method involves some form of chlorine or its compounds such as chloramine or chlorine dioxide. Chlorine is a strong oxidant that rapidly kills many harmful micro-organisms. Because chlorine is a toxic gas, there is a danger of a release associated with its use. This problem is avoided by the use of sodium hypochlorite, which is a relatively inexpensive solution that releases free chlorine when dissolved in water. Chlorine solutions can be generated on site by electrolyzing common salt solutions. A solid form, calcium hypochlorite, releases chlorine on contact with water. Generally this process used to disinfect or destruction of pathogenic organism and odor control.

  1. Multi grade Filtration (Sand Filters)

Chlorinated Raw Water is pumped through auto Multi Grade Filter to reduce turbidity and suspended solids. It consists of graded sand and gravel which removes suspended particles from the feed water. MGF is designed for either once a day backwash or when the pressure drop across MGF is more than 0.5 bar. Normal Operation, Rinsing & Backwash of the MGF is done automatically.

  1. Softener

Hardness causes scaling and salt precipitation on the RO membranes and other equipment’s like piping, Storage tanks etc.; hence an IX Softener is used to replace divalent ions like Ca & Mg with Na. The softener is designed for hardness reduction up to 5 ppm as CaCO3. After producing the design water quantity the Softener is regenerated with Brine solution and is ready for operation again. Normal Operation, Rinsing, Backwash and regeneration of the Softener is done automatically.

4. Ultra filtration System

The UF is effective and useful in achieving a consistent RO feed water quality having a SDI less than 3. Important advantages of UF in the RO feed are as below:

  • Reduced membrane fouling due to particulate matter and hence longer membrane life
  • Acts as an effective barrier against bacteria and organics hence reduced membrane sanitization
  • The Ultra Filtration System consists of HFF (Hollow Fine Fibres) modules made out of PVDF or modified PES which have a very high chemicals tolerance.
  • The UF system operation involves several steps like backwash, forward flush, chemically enhanced backwash etc. All the sequential action is carried out automatically based on the pre-programmed sequential logic. The water generated from ultra-filtration is then collected in UF Treated Water Storage Tank.

5. Dosing Systems

  • ANTISCALENT DOSING SYSTEM: – Dosage of Anti scalent solution into RO Feed water to control the scaling of RO membrane due to high amount of silica in raw water. Sodium hexametaphosphate (NaPO3)6 dosing is considered for this purpose.
  • SMBS DOSING SYSTEM: – The de chlorination is carried out with the help of Sodium Meta Bi-Sulphate, which removes the presence of chlorine in feed water. This dosing helps to avoid oxidation of membranes. The SMBS solution should be freshly prepared daily.
  • pH Dosing:-  pH correction dosing is done to keep the pH in the range of 7.8 to 8.85. Carbon dioxide content in water considered as important water & process parameter. As carbon dioxide in gaseous form pass easily the RO membrane & could affect negatively on Softener process. pH dosing is to eliminate carbon dioxide before Softener which formed as ion due to pH dosing and can be easily eliminated by the RO process. NaOH dosing is considered for this purpose.

Purified Water Generation System (RO+ EDI)

  1. Reverse Osmosis

Reverse Osmosis is a water purification process that uses a partially permeable membrane to separate ions, unwanted molecules and larger particles from drinking water. In reverse osmosis, an applied pressure is used to overcome osmotic pressure, a colligative property that is driven by chemical potential differences of the solvent, a thermodynamic parameter. Reverse osmosis can remove many types of dissolved and suspended chemical species as well as biological ones (principally bacteria) from water, and is used in both industrial processes and the production of potable water. The result is that the solute is retained on the pressurized side of the membrane and the pure solvent is allowed to pass to the other side. To be “selective”, this membrane should not allow large molecules or ions through the pores (holes), but should allow smaller components of the solution (such as solvent molecules, i.e., water, H2O) to pass freely.

2. EDI System

The typical EDI installation has the following components: anode and cathode, anion exchange membrane, cation exchange membrane and the resin. The most simplified configuration consist in 3 compartments, to increase the production these number can be increased.

The cations flow towards the cathode and the anions flows toward the anode. Only anions can go through the anion exchange membrane and only cations can go through the cation exchange membrane. This configuration allows anions and cations to only flow in one direction because of the membranes and the electric force, leaving the feed water free of ions, (deionized water).

You will get efficient and thoughtful service from ShekeSaisi.

The concentration flows (right and left of the feed flow) are rejected and they can be wasted, recycled, or use in another process. The purpose of the ion exchange resin is to maintain stable conductance of the feed water. Without the resins, the conductance will drop dramatically as the concentration of ions is decreasing. Such drop off of conductance makes it very difficult to eliminate 100% of the ions, but using resins makes it possible.

The Four Pillars of Pharmaceutical Water Quality - Mettler Toledo

Conductivity measures a water's ability to conduct electricity, indirectly indicating the presence of dissolved ionic contaminants. 

Pure water itself is a poor conductor of electricity, lacking the charged particles necessary for efficient current flow. However, the presence of dissolved salts, minerals, and some organic matter disrupts this neutrality. When an electric field is applied to the water, these dissolved compounds dissociate into charged ions (cations and anions). Because pure water molecules (H2O) are neutral, these ions migrate toward the oppositely charged electrodes, facilitating the flow of electricity. The more ions present, the higher the water's conductivity. Thus, high conductivity can signal issues like high minerality or industrial waste contamination.

Within the pharmaceutical water production process, conductivity monitoring is crucial at various stages:

  • Feed Water Monitoring: As the raw water enters the purification process, its conductivity is measured. High readings can indicate contamination from minerals present in groundwater or industrial pollutants. This early detection allows for appropriate pre-treatment steps before the water advances further.
  • Reverse Osmosis (RO) Permeate Monitoring: The RO membrane acts as a physical barrier, selectively allowing water molecules to pass through while rejecting larger ions. Real-time conductivity monitoring of the RO permeate – the treated water emerging from the membrane – serves as a crucial performance indicator. A sudden rise in conductivity could signal a compromised membrane, allowing the passage of unwanted ionic contaminants.
  • Electrodeionization (EDI) Effluent Monitoring: EDI further polishes the RO permeate by utilizing electrically charged resins to remove remaining ions. Continuous conductivity monitoring of the EDI effluent ensures the process is functioning optimally, achieving the ultrapure water (UPW) quality required by various pharmacopeias.
  • Storage and Distribution Monitoring: Conductivity is monitored at storage tanks and within the return loop as a final safeguard to ensure the quality of ultrapure water (UPW) throughout the distribution system. This vital data safeguards against potential contamination and meets stringent regulatory requirements.

Real-time conductivity monitoring allows for immediate detection of any deviations in these critical stages, safeguarding water quality throughout the entire production process and ensuring consistent delivery of pristine pharmaceutical water for the production of vital medications.

Total organic carbon (TOC) represents the total amount of organic carbon present in water. Excessive TOC can indicate the presence of organic contaminants like decaying organic matter, microorganisms, or industrial byproducts. Even trace amounts of these contaminants can significantly impact the quality and safety of pharmaceutical products.

TOC monitoring is particularly important for:

  • Ultrafiltration (UF) Permeate Monitoring: The UF membrane works as a microscopic sieve. Its pores are specifically sized to allow water molecules and tiny dissolved particles to slip through while prohibiting larger contaminants from passing. This selective filtration process removes unwanted organic molecules like decaying matter, microorganisms, and industrial byproducts. Real-time TOC monitoring of the treated water (permeate) following the membrane serves as a vital performance indicator. A sudden spike in TOC could signal a compromised membrane or organic matter breakthrough, prompting corrective actions to maintain the critical purity of pharmaceutical water.

  • Organic Removal Processes (e.g., activated carbon): Activated carbon is a highly adsorbent material that effectively removes a wide range of organic compounds from water. Monitoring TOC downstream of activated carbon filters ensures the process is functioning optimally and maintaining low organic carbon levels.
  • Storage and Distribution Monitoring: TOC monitoring in the return loop acts as a critical failsafe during storage and distribution. By measuring TOC, this process detects any organic contaminants like decaying matter, microorganisms, or industrial byproducts that may have entered the UPW. Measuring TOC at the return loop captures any potential organic contamination circulating throughout the system and can be used for regulatory reporting.

On-line continuous TOC monitoring provides full spectrum insight into organic carbon levels and potential excursions, enabling proactive adjustments to treatment processes and guaranteeing consistent water quality.

Within the realm of pharmaceutical water production, the term "bioburden" is of critical significance. It refers to the quantitative measure of the total number of viable microorganisms, encompassing bacteria, fungi, and even some protozoa, present in a given water sample. A high bioburden signifies a potential health risk associated with the intrusion of these unwanted microbes. Furthermore, it can indicate inefficiencies within the water purification processes designed to eliminate them.

Monitoring bioburden is paramount for:

  • The Entire Water Production Process: Regular bioburden assessments throughout various stages of the water purification process are crucial. This continuous monitoring helps identify potential sources of microbial contamination and ensures consistent low microbial levels are maintained within the entire water system.

  • Post-Disinfection Stages: Disinfection processes, such as ultraviolet (UV) treatment or ozone application, are employed to eliminate microorganisms from the water. Bioburden monitoring after these disinfection stages serves as a critical verification step. A low bioburden reading following disinfection confirms the effectiveness of the chosen technique in achieving microbial inactivation. Conversely, a high bioburden reading indicates a potential breach in the disinfection process, necessitating investigation and corrective actions.

  • Storage and Distribution Monitoring: Functioning as the final line of defense, bioburden monitoring is conducted at storage tanks and within the return loop. The focus now is on detecting microorganisms that might have snuck through the system. The best place to measure for this is in the return loop, since it’s measuring the water already produced and at the same time that's being used. Regular monitoring here and taking any necessary corrective actions ensures product safety and compliance with regulations.

Rapid and constant bioburden monitoring empowers companies to implement preventative measures to control microbial growth. This proactive approach minimizes the risk of contamination events and ensures reliable adherence to stringent microbiological quality standards set forth by pharmacopeias like the USP.

Dissolved ozone (O3) emerges as a powerful weapon in the fight for microbiologically pure pharmaceutical water. Its strength lies in its unique chemistry: acting as a potent oxidizing agent, ozone disrupts the integrity and kills bacteria and viruses by readily reacting with electron-rich molecules in their cell walls. This oxidizing power extends to even chlorine-resistant foes like cysts and certain viruses. Moreover, ozone boasts rapid disinfection kinetics, offering swift action compared to some traditional methods. Finally, it aligns perfectly with the "no added substances" principle as it naturally decomposes back into oxygen (O2) upon exposure to ultraviolet (UV) light, leaving no residual concerns in the treated water.

Monitoring dissolved ozone is essential for the following:

  • Disinfection Process Control: Maintaining optimal ozone concentration is a delicate balancing act. While a level too low might leave microbes unfazed, excessively high levels can generate harmful derivatives. By considering water quality parameters like pH, temperature, and organic content, adjustments to ozone dosage or contact time can be made to ensure the most effective disinfection possible.

  • Compliance with Disinfectant Residual Regulations: Pharmacopeias and regulatory bodies set limitations on residual disinfectant levels in treated water. For ozone, these limitations aim to balance the need for microbial control with minimizing potential byproduct formation. Continuous dissolved ozone monitoring allows for adjustments in the disinfection process to maintain residual ozone levels within acceptable limits.

Real-time dissolved ozone monitoring provides continuous insight into ozone levels, enabling operators to leverage real-time data to immediately fine-tune ozone dosages or contact time, ensuring effective disinfection and regulatory compliance.

For decades, the cornerstone of pharmaceutical water quality control has been the "grab sampling" method. Here, water samples are meticulously collected at predetermined intervals and whisked away to a laboratory for analysis. While this approach offers valuable data points, its inherent limitations can pose significant threats to water purity.

The time between sample collection and receiving results can be substantial. This critical lag can mask transient contamination events or quality excursions between sampling points. By the time an issue is identified, a significant volume of potentially contaminated water may have already been produced.

Furthermore, grab sampling offers a limited snapshot of water quality at a specific time and location. It fails to capture the dynamic nature of water purification processes, potentially missing critical moments of vulnerability to contamination.

Real-time monitoring offers a new era of water quality control, offering a dynamic and continuous window into the intricate workings of pharmaceutical water purification. This approach strategically deploys online analyzers at critical points within the system, transforming water quality monitoring from a reactive to a proactive endeavor. These analyzers function as vigilant sentinels, continuously measuring essential water testing parameters.

At METTLER TOLEDO, we understand the paramount importance of pharmaceutical water purity. Compromises in this critical area can have far-reaching consequences. That's why we offer a comprehensive solution – real-time monitoring of TOC, conductivity, dissolved ozone, and bioburden – empowering you to gain unparalleled control and insight into your water purification process.

With an all-encompassing suite of analyzers, we help pharmaceutical water manufacturers simplify system integration, data management, and operator training to facilitate a smooth transition to a robust real-time monitoring environment. Our proactive approach safeguards water quality, minimizes contamination risks, and ultimately supports the consistent production of drugs and medications.

For more pharmaceutical water systeminformation, please contact us. We will provide professional answers.