Water is the primary raw material used in the Pharma industry. It is used as a raw material in manufacturing pharmaceutical products in various forms, such as parenteral, oral solid, and liquid. It is also used in laboratories for sample preparation and chemical reagents for using it across multiple test forms.
Water for pharmaceuticals must be carefully produced, stored, and distributed with a high degree of quality and contamination control. Because if not carefully controlled, contamination can be developed in water and become hazardous for every pharma process where it is being used. So to mitigate and prevent risks related to contamination, and other hazards, water must meet the required quality standards.
Standard processes in generating water for pharmaceutical use
There are various methods and equipment to generate water for pharmaceutical use. Every process can generate water of specific specifications, which can then be used for a particular production process.
The process and equipment used in water generation can vary depending on the type of water, its application, product attributes, and quality requirements. Overall, the water generation process can be categorized into three different procedures
Water generation refers to the techniques, equipment, and processes used in generating water for pharmaceutical use.
Water generation usually consists of a series of equipment that performs various processes. Water enters the process cycle in a raw form, and as it advances from one equipment or stage to its next level, different change occurs in the properties of water.
When water comes out of the final process or stage, it contains the required essential properties for use in the Pharmaceutical process and application.
Generally, the capacity of water generation equipment is mentioned in liter/hour, i.e., the amount of water indicated in liters that can be produced in one hour.
Water generated from the generation plant is not directly sent to its intended application area. Instead, it is stored in bulk storage vessels with large storage capacities. The capacities of these storage vessels are indicated in large quantities, typically in thousands of liters, such as 6000 liters.
The main reason for storing Pharmaceutical water is to provide the required quantities per the production process requirement. Because sometimes, the capacity of water generation does not match the amount of water needed for the Pharmaceutical facility. Secondly, there is expected to be no demand in the Pharma plant during water generation hours, and water will be stored to provide whenever there is a requirement. So far, for these reasons, and like these, water is stored in a storage section before distributing it.
Storage mainly consists of vessels that provide suitable storage capacity. The vessels should prevent contamination and bio-burden development in the stored water. Storage vessels must also ensure that water properties are retained and should not disturb these.
Storage vessels should have specific, pharma-grade characteristics that prevent water degradation and retain their properties.
Storage vessels must comprise SS 316L, which provides excellent resistance to chemical reactions between water and vessel material. The internal surface of the vessel should be electro-polished with a mirror finish.
Storage vessels also contain specialized accessories like level transmitters and pressure gauges. Their basic purpose is to monitor the water inside the vessel and keep an eye on water inflow and outflow.
Water distribution is a mechanism for distributing stored water at its intended point of use, such as manufacturing departments and laboratories. It consists of a network of piping laid down across a facility, with an opening provided at the point of use. It also includes a pump used to pump the water in the piping network.
Like a storage vessel, the piping is also made up of SS 316L, with an electro-polished and mirror finish. The distribution system also contains instrumentation and accessories such as gauges, flow meters conductivity, and temperature sensors at the appropriate locations. Their primary purpose is to monitor and control the flow of water. They are also used to monitor quality attributes and condition of circulating water.
Types of water for pharmaceutical use
For the pharmaceutical industry, there are various categories of water. However, the pharma industry commonly uses two types of water - purified water and water for Injection.
Purified water is used to prepare medicines other than aseptic and parenteral products. They are also used for cleaning equipment, such as cleaning a dryer machine after every batch or product. It is also used for testing purposes in the laboratory, such as preparing test samples and assays.
The minimum requirement for generating purified water is drinking water supplied to the purified water plant from the input.
A purified water plant consists of a series of subsystems to remove impurities. Some important subsystems include the following.
Pretreatment: This is the first stage of the purified water plant to remove suspended particles and consists of a multimedia filter.
Water softener: It removes hardness-causing materials such as calcium and magnesium. It employs an ion exchange method that effectively replaces active ions.
Reverse osmosis: The output water from the water softener is made to pass through the reverse osmosis section. It consists of a semipermeable membrane to separate impurities in the water. The water to be purified passes through the RO membrane with high pressure. The reason for high-pressure water is to overcome osmotic pressure.
As water passes through the RO membrane, all impurities are removed and discharged from the water plant through the rejection system.
Electrodeionization EDI: Electrodeionization removes ionized substances from the output of the RO stage. It uses DC power to create an electric field, forcing ionized substances to separate from the water.
Ultrafiltration: Ultrafiltration is the final stage, through which output water from
the electrode ionization stage passes through it. It is used to remove substances having higher molecular weight or size.
Water for Injection
Water for Injection is mainly used in manufacturing parenteral or for products where specialized control of contamination or endotoxin is required. WFI is also used for the final rinsing of equipment to process aseptic and parenteral products, where purified water is used in cleaning.
Water for Injection has strict control of bacteria and introduction compared to purified water.
Water for Injection is produced from drinking or purified water. The most common method of generating water for Injection is distillation. However, many latest water plants also use membrane-based techniques for generating water for Injection. This article will discuss the most common method, i.e., the distillation.
The feed water enters the input section, where it is heated to convert into steam. When infeed water is converted into steam, it leaves behind all the impurities, bacteria, and other contaminants because its boiling point is higher than water's. At the boiling point of water, there are no significant changes in these impurities, and they remain in their state.
These impurities remain in their state and leave the plant through discharge or rejected water outlet.
In the next stage, the steam is again converted into water by lowering the temperature. It is performed by cooling columns, in which cooled water circulates to lower the temperature well below the boiling point of water.
The water converted from steam is called Water for Injection, which is then transferred to tanks for storage.
Applications of water for pharmaceutical use
Let's discuss some applications of water in the pharmaceutical industry.
The most common application of water in the pharmaceutical industry is product manufacturing. It is used as an excipient for different chemicals in a pharma product. The type of water used depends upon the product and type of process used for manufacturing Pharmaceutical products.
Purified water is commonly used for non-parenteral products such as tablets and oral liquid. Because these products are less critical for human consumption, purified water having less critical contamination control can be safely used.
Water for Injection is used for parental products because these products are critical for human consumption. Water for Injection having strict contamination control can effectively provide the desired contamination control requirements.
Specification of water required for manufacturing Pharma products is developed during the product development stage. The water specification must be strictly followed under the regulatory or quality requirement guidelines.
Another area where Pharmaceutical water is used is for testing purposes—the laboratory in the Pharma facility. Water is used in quality control laboratories for various purposes, such as buffer preparation. Pharmaceutical water is used to prepare samples of Pharma products to be used in different analytical instruments. For example, in pH meter and spectrophotometer.
If appropriate Pharma water having the desired product specification is not used, it will disturb the testing procedure and deviate results from its standard values.
Pharmaceutical water is also used for cleaning equipment, utensils, and other accessories standard in the pharma manufacturing process. It is used to clear the remaining product on equipment and neutralize the effect of Pharmaceutical components after every batch and product.
For parenteral products, equipment and accessories are cleaned with purified water. After cleaning with purified water, WFI is used for rinsing to remove the effects of purified water.
For other products, purified water is used for cleaning purposes.