One of the most pronounced ingredients in any pharmaceutical engineering is water. Water serves as a solvent and ingredient for formulation in many pharmaceutical procedures. Special care and attention must, therefore, be taken to ensure that the water used, meets the standard quality for purified water. Water is purified to remove impurities and prevent microbes which might cause contamination of products.
For water to be rendered purified, it is passed through different types of industrial water purification systems including distillation, filtration, reverse osmosis and ion exchange. However, other suitable procedures such as ultrafiltration can also be used. Purified water is used in pharmaceutical applications such as preparation of pharmaceutical products and cleaning of certain equipment and systems.
The primary source of purified water is drinking water. As such, the feed water must be protected from microbial proliferation. When considering any type of industrial water filtration systems, it is essential to consider periodic sanitization because microbes may thrive during production, storage, and distribution. One of the general principles which apply to any type of purified water system in pharmaceuticals entails prevention of any microbial and physical re-contamination. The justification for use of purified water lies on the premise that purified water contains less solid impurities, estimated to be about one percent, than ordinary feed water.
To achieve the above level of water purity, pharmaceutical facilities use a combination of purification methods. Different types of water systems are designed on the basis production, feed water quality and regulatory requirements.
1. Reverse Osmosis (RO) System
2. Deionization (DI) System
3. Electrodeionization (EDI) System
4. Distillation System
5. Combination Systems (Hybrid Units)
Let’s explore each type of system in detail
This system removes ionic impurities from water by exchanging them with hydrogen (H+) and hydroxyl (OH-) ions. In ion exchange system water passes through ion exchange region columns containing cation exchange resin that replaces positive ions like Ca++, Mg++, NA+ etc. with H+ ions and anion exchange resin that replaces negative ions like Cl-, SO4--, NO3- with OH- ions. The H+ plus and OH- ions combine and form pure water.
Some common configurations for purified water systems are:
Softener → RO → UV → EDI
RO → Mixed Bed DI → UV → Ultrafiltration
Two-pass RO System
Purified water systems are the backbone of pharmaceutical manufacturing facilities because purified water is used in many processes during manufacturing. The choice of system like RO, EDI, DI or distillation depends on production requirements, regulatory standards and cost considerations.
Modern pharmaceutical facilities generally use RO + EDI hybrid systems for efficient and continuous generation of high quality purified water. However, the system design, validation and maintenance are also critical parameters to ensure quality of purified water and regulatory compliance.
A well-designed and validated purified water system not only ensures safe and effective product manufacturing but also protects patient health and company reputation by meeting the highest standards of purity and reliability.
For water to be rendered purified, it is passed through different types of industrial water purification systems including distillation, filtration, reverse osmosis and ion exchange. However, other suitable procedures such as ultrafiltration can also be used. Purified water is used in pharmaceutical applications such as preparation of pharmaceutical products and cleaning of certain equipment and systems.
The primary source of purified water is drinking water. As such, the feed water must be protected from microbial proliferation. When considering any type of industrial water filtration systems, it is essential to consider periodic sanitization because microbes may thrive during production, storage, and distribution. One of the general principles which apply to any type of purified water system in pharmaceuticals entails prevention of any microbial and physical re-contamination. The justification for use of purified water lies on the premise that purified water contains less solid impurities, estimated to be about one percent, than ordinary feed water.
Importance of Purified Water in Pharmaceuticals
Purified water is used in many steps of pharmaceutical manufacturing including:- Preparation of non-sterile dosage forms like syrups, ointments and tablets.
- Cleaning of manufacturing equipment and vessels.
- Preparation of culture media for microbial analysis.
- Utility water for laboratory and analytical instruments.
Quality Standards for Purified Water
According to pharmacopeial standards purified water must meet the following quality parameters.| Parameter | Specification (Typical USP Limit) |
| Conductivity | ≤ 1.3 µS/cm at 25°C |
| Total Organic Carbon (TOC) | ≤ 500 ppb |
| Microbial Count | ≤ 100 CFU/mL |
| Nitrates | ≤ 0.2 ppm |
| Heavy Metals | ≤ 0.1 ppm |
| pH | 5.0–7.0 |
To achieve the above level of water purity, pharmaceutical facilities use a combination of purification methods. Different types of water systems are designed on the basis production, feed water quality and regulatory requirements.
Types of Purified Water Systems
The purified water systems used in pharmaceutical industry are classified on the basis of the purification method used. The most commonly used water systems are:1. Reverse Osmosis (RO) System
2. Deionization (DI) System
3. Electrodeionization (EDI) System
4. Distillation System
5. Combination Systems (Hybrid Units)
Let’s explore each type of system in detail
1. Reverse Osmosis (RO) System
Reverse osmosis (RO) applies pressure to the concentrated solution in osmosis process, thereby disrupting the natural osmotic flow. As a result, water starts flowing from the more concentrated solution to the less concentrated solution. It removes dissolved solids, ions, bacteria and organic contaminants from water. It is strongly advised that if RO systems are being utilized for pharmaceutical manufacturing, they should be designed to control the growth of bacteria. RO units are often susceptible to microbial fouling and must be cleaned thoroughly and regularly.System Components
- Prefiltration units like cartridge filters, activated carbon filters, sand filters etc.
- High pressure pump.
- Ultra filtration unit.
- RO membrane system.
- Post treatment units like UV and final filter.
Advantages
- Efficient and cost effective.
- Removes up to 99% of total dissolved solids.
- Provides continues water supply and easy to automate.
Limitations
- Sensitive fouling and scaling.
- Requires Regular membrane cleaning and replacement.
- Unable to completely remove dissolved gases or CO2.
Use in Pharmaceuticals
RO systems most commonly used purified water generation systems in pharmaceutical industry due to their efficiency and low operating cost. Generally, they are combined with other technologies like UV sterilization, EDI system or ultra filtration for enhanced purity of water.2. Deionization (DI) System
Deionization or ion exchange is one of the most desirable types of purified water treatments. It involves separation of water-soluble undesirable ions and exchanging those ions with desirable ones. Therefore, this water treatment technology focuses on altering the ionic composition in a desirable direction. Due to its ease of operation, minimal maintenance, the ion exchange method is mostly preferred in pharmaceuticals as a type of purified water system.This system removes ionic impurities from water by exchanging them with hydrogen (H+) and hydroxyl (OH-) ions. In ion exchange system water passes through ion exchange region columns containing cation exchange resin that replaces positive ions like Ca++, Mg++, NA+ etc. with H+ ions and anion exchange resin that replaces negative ions like Cl-, SO4--, NO3- with OH- ions. The H+ plus and OH- ions combine and form pure water.
Advantages
- This system produces water with low conductivity and ionic impurities.
- It has relatively low initial cost.
- It is suitable for medium scale purified water systems.
Limitations
- It doesn’t remove organic matter or microorganisms from water.
- It requires frequent resin generation using acids and alkalis.
- It generates chemical waste.
Use in Pharmaceuticals
Deionization systems are used as feed water system before RO treatment to achieve pharmacopeial grade purified water.3. Electrodeionization (EDI) System
EDI systems use electrodeionization system that combines ion exchange and electrodialysis that continuously removes ionic impurities without the need of chemical regeneration. Water flows through ion exchange resin placed between ion selective membranes. When an electric current is applied ions move across the membrane cations towards the cathode and anions toward the anode leaving behind purified water.Advantages
- It provides continuous operation without any chemical regeneration.
- Low maintenance and no environmental impact.
- It provides consistent water quality with conductivity less than 0.1 µS/cm.
Limitations
- This system is sensitive to feed water quality and requires pretreatment of water.
- It has a high installation cost compared to DI systems.
Use in Pharmaceuticals
EDI is generally combined with RO systems (RO+EDI system) to produce purified water that meets USB and EP specifications. It is considered a modern and sustainable water purification system for pharmaceutical industry.4. Distillation System
Distillation is a thermal process that involves boiling the feed water and then condensing the steam to produce high quality purified water. In a distillation unit the water is heated until it vaporizes and the steam produced that leaves impurities behind it like salts, heavy metals and microorganisms. The steam is then cooled and condensed into liquid form to in the form of purified water.Advantages
- Distillation process produces high quality water with very low impurities.
- It effectively removes pyrogens, endotoxins and microorganisms.
- It is a simple and reliable method for producing water for injection (WFI)
Limitations
- It consumes high energy in the form of electricity.
- It requires maintenance of heating elements and condensers.
- It is not economical for large scale purified water production.
Use in Pharmaceuticals
Distillation system is mainly used for WFI generation but sometimes small manufacturing facilities use destination to produce purified water.5. Combination or Hybrid Systems
Multistage water purification systems are used by pharmaceutical manufacturers to get high purity and meet pharmacopeial standards. They combine two or more systems to get maximum efficiency and purity.Some common configurations for purified water systems are:
Softener → RO → UV → EDI
RO → Mixed Bed DI → UV → Ultrafiltration
Two-pass RO System
Advantages
- Hybrid systems enhance efficiency of system to remove chemical and microbial impurities.
- It provides continuous operation with minimum downtime.
- Low operation cost due to low maintenance and downtime.
Use in Pharmaceuticals
Hybrid systems are the standard for modern manufacturing plants where high water demand and consistent quality are required for GMP compliance. Generally, pharmaceutical manufacturing facilities have Hybrid Systems for purified water generation.Storage and Distribution of Purified Water
It is important to maintain the purified water quality during its storage and distribution until it is used in manufacturing process. Following are some key points that should be considered during storage and distribution of purified water.- Storage tank must be made up of stainless steel 316 L.
- Continuous recirculation loop is required to prevent stagnation of water.
- UV sterilization and 0.2 µm filters in the loop must be installed to remove any microbial contamination.
- Heated water distribution (70–80°C) must be considered to control microwave growth.
- Regular sanitization using hot water, ozone or hydrogen peroxide should be done.
Regulatory Requirements for Purified Water Systems
Regulatory agencies such as USFDA, EMA and WHO require a water system that produces high quality water consistently. A purified water system should be:- Designed to prevent microbial contamination and biofilm formation.
- Validated to demonstrate consistent water quality.
- Have standard operating procedures (SOPs) for operation, maintenance and sanitization of water system.
- Included online monitoring for conductivity, TOC and microbial count.
- Maintained traceable records of water generation and quality testing.
Purified water systems are the backbone of pharmaceutical manufacturing facilities because purified water is used in many processes during manufacturing. The choice of system like RO, EDI, DI or distillation depends on production requirements, regulatory standards and cost considerations.
Modern pharmaceutical facilities generally use RO + EDI hybrid systems for efficient and continuous generation of high quality purified water. However, the system design, validation and maintenance are also critical parameters to ensure quality of purified water and regulatory compliance.
A well-designed and validated purified water system not only ensures safe and effective product manufacturing but also protects patient health and company reputation by meeting the highest standards of purity and reliability.
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ReplyDeleteWhat about the flow rate of purified water and distilled water in return loop after user points
ReplyDeleteWhat about flow rate of purified water and WFI in return loops and how much is it
ReplyDeleteVelocity shall be maintained more than 1.2meter per second
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