TSA understands the value of water in the pharmaceutical industry. Water serves various purposes in pharma and must meet the quality standards of regulatory authorities like the WHO and EU. Since pristine water is rarely available, it must be purified to meet our specific requirements.
In this blog, we will discuss the types of impurities commonly found in water and the categories of water based on their applications and quality. Keep reading to learn more!
Types of Impurities in Water
The most commonly found impurities that degrade water are:
Dissolved Impurities
These include dissolved gases, inorganic salts, and metallic and organic impurities.
- Dissolved gases: Chlorine, Ammonia, Carbon dioxide, and Hydrogen sulfide are sparingly soluble in water.
- Inorganic salts or Metallic impurities: Metallic salts readily dissolve in water. They dissociate into charged ions i.e. cations (a++, Mg++, Na+ , K+ , Fe++, Al+++) and anions (CO3–, Cl–, SO4–, NO3)
- Organic Impurities include hydrocarbons, alcohols, aldehydes and ketones.
Suspended Impurities
The slightly larger particles (1 micrometre to several millimetres) that do not dissolve in water and remain suspended are suspended impurities. Insoluble Solids, Dust, Fine Sand, Clay, Animal Particles, and Oil Globules are some of the suspended impurities, to name a few. The measure of the total amount of suspended solids indicates the total amount of suspended impurities present in water.
Colloidal Impurities
These are the smaller-sized impurities (1 nanometre to 1 micrometre in diameter) in water in all three states: solid, liquid or gaseous. Some colloidal impurities commonly found in water are clay particles, Silica, Al(OH)3, Fe(OH)3, organic matter, and dye particles.
Microbial Impurities
The degradation of water quality due to microbes like algae, bacteria, protozoa, viruses, fungi, parasites and their eggs is called microbial contamination. The water used in pharma must be free from any microbial impurities.
Categories of Water
Water used for pharmaceutical applications is classified into different grades, many of which are detailed in USP monographs, specifying their uses, acceptable preparation methods, and quality attributes. The required grade of water quality varies depending on the specific pharmaceutical application.
The Pharmaceutical water systems are broadly classified into the following two categories:
Bulk Water
The water produced in large volumes on-site of its use is referred to as Bulk water. There are different types of Bulk waters, and they do not have specific monographs. Hence, they are not obliged to strictly follow the production methods outlined in monographs. The types of Bulk water are:
1. Purified Water
Purified water is produced by treating potable water as a feed water source. The water treatment methods followed include deionisation, filtration, distillation, ion exchange, reverse osmosis, and other suitable purification processes.
The Purified water generated is free of ionic, organic, chemical, and microbial impurities. This water is typically used as an excipient in non-parenteral preparations, sanitisation, and non-parenteral product-contact components. The Purified Water is also the analytical tool for specified tests and assays.
TSA offers Purified Water Generation Systems with advanced closed-loop recirculation systems for sustainable operations with optional automation of sanitisation and sterilisation processes. These systems are skid mounted and comply with US FDA 21 CFR Part 11 and GAMP5.
A water purification system producing Purified Water in bulk is highly vulnerable to the tenacious microbial films. These biofilms produce polysaccharides, proteins, and endotoxins (produced by viable bacteria) that contaminate purified water and degrade its quality.
In this discussion, “water” refers to Purified Water when used without descriptive adjectives or clauses.
2. Highly Purified Water
Pharmacopeia Europe has established unique specifications specifically for Highly Purified Water. This type of water, like Purified Water, also uses potable water as its source. While Highly Purified Water shares the endotoxin limits with Water for Injection, the treatment processes differ significantly.
The Highly Purified Water is generated by combining different methods, e.g., double-pass reverse osmosis coupled with ultrafiltration. Only in exceptional cases is another qualified industrial water treatment process used to produce HPW.
3. Water for Injection (WFI)
Water For Injection is used as an excipient to produce parenteral and other preparations. It is also used to clean equipment and the components that come in direct contact with the parenteral products. WFI must have negligible endotoxin content. Also, the purifying systems must eliminate any traces of endotoxins in the water.
The systems used to store and distribute WFI should prevent any microbial contamination. TSA’s Multi-column Distillation Plant is a uniquely efficient purification system with flow rates ranging from 80 LPH to 5000 LPH. It delivers optimised purity for your advanced sterile processes (WFI) and offers quick start-up with enhanced performance and energy savings.
Hence, the WFI is usually produced through distillation as it ensures the chemical and bacterial endotoxin content lies within the permissible limits of the U.S. EPA, EU, Japan and WHO guidelines.
4. Water for Hemodialysis
Water for Hemodialysis is used to dilute the haemodialysis concentrate solutions. This water is produced on-site using potable water that meets the standards set by EPA. After eradicating chemical and microbial contam from water, it is packaged and stored in unreactive containers to preserve the water quality. An unreactive container is typically made from corrosion-resistant materials.
5. Pure Steam or Clean Steam
Pure Steam or Clean Steam comes directly in contact with the surface of the equipment used in the operations, and it is primarily used to sterilize the equipment or remove the co-deposited impurities.
Packaged Water
When purifying the water, it is packaged to prevent any quality deterioration. It can be further categorized based on applications, packaging shelflife and other quality specifications.
1. Sterile Purified Water
The Sterile Purified water is packaged to maintain its quality and is used to prepare non-parenteral compendial dosage forms. It is also used to validate the Pharma Water systems as well.
2. Sterile Water for Injection (SWFI)
The sterile packaged water for injection is referred to as “Sterile Water for Injection”. It is used for extemporaneous prescription compounding and as a sterile diluent for parenteral products.
The SWFI is used when a small quantity of water is required, and there is no access to a validated water system. It is typically available in single-dose containers, usually not larger than 1L.
3. Bacteriostatic Water for Injection
The bacteriostatic water for injection is the water for injection with the bacteriostatic agent to cease the cell division in microbes. This water is sterile and is used as a diluent in parenteral preparation. It is packaged in single-dose or multiple-dose containers, not larger than 30 ml.
4. Sterile Water for Irrigation
As per the USP, Sterile Water for Irrigation is non-pyrogenic water for injection, which permits rapid content delivery and has applications like sterile irrigation. It can also be used for washing, rinsing, and dilution.
Sterile water for irrigation is used only for single-dose or short-procedure irrigation, and when smaller volumes are required, the unused portion is to be discarded.
5. Sterile Water for Inhalation
When sterilised and packaged, the Water for Injection is used as Water for Inhalation. As the name suggests, this water is used to prepare Inhalation solutions. However, it is unsuitable for parenteral use as it has less stringent specifications for bacterial endotoxins than WFI.
Conclusion
The water must be treated according to the quality standards of regulatory authorities. The treatment systems must ensure no contaminants are added to the water during the process.
At TSA, we provide high-purity water systems to generate purified water, water for injection, and pure steam that comply with the most stringent standards in the world!
Contact us at TSA to craft solutions to your problems now!
FAQs
- What are the common types of impurities found in water used in pharmaceuticals?
Common impurities include particulate matter, microorganisms (bacteria, viruses, and fungi), organic compounds, inorganic substances (salts and heavy metals), and endotoxins.
- What is the difference between Purified Water and Water for Injection (WFI)?
Purified Water is treated to meet specific quality standards but is not necessarily sterile. Water for Injection is a higher grade of water that is sterile and free of pyrogens, suitable for use in the preparation of injectable pharmaceuticals.
- What is Highly Purified Water, and how does it differ from Purified Water?
Highly Purified Water has specific regulatory requirements set by Pharmacopeia Europe and is treated to a higher standard than Purified Water. It also shares the endotoxin limits with Water for Injection, but the treatment process varies.
- How do regulatory standards impact the quality of water used in pharmaceuticals?
Regulatory authorities such as the WHO and EU establish strict quality standards that pharmaceutical companies must follow to ensure the safety and efficacy of their products. Non-compliance can lead to product recalls or legal issues.
- What are endotoxins, and why are they important in pharmaceutical water?
Endotoxins are toxic substances released from the cell walls of certain bacteria. Their presence in pharmaceutical water can lead to adverse reactions when injected, making it crucial to limit their concentration in water for injection and highly purified water.
