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Pharmaceutical Water Systems | Compliance by Design


This guide is designed to provide a valuable and convenient information resource to aid in the design of pharma water systems that are compliant with the requirements of global pharmacopeias. It offers vital information on topics including requirements for source bulk waters, control of biofilms, and the three stages of water systems.

Topics Covered

1. Initial Design Considerations.

2. General Information on Water Sources and Contaminants

2.1 Contaminants in water

2.2 Pharmacopeia requirements for source water

3. Production Requirements for Bulk Waters

3.1 Basic water system monitoring requirements

3.2 Purified Water (PW)-USP37-NF32

3.3 Water for Injection (WFI)-USP37- NF32

4. Biofilm

5. Designing and Engineering Pharmaceutical Water Systems

5.1 Pre-treatment

5.2 Purification

5.3 Storage and distribution

6. Instrumentation Recommendations for Pharmaceutical Water Systems

Initial Design Considerations

For the production of pharmaceutical waters, source water must be treated using a combination of purification steps that are designed to remove specific types of impurities. The combination and order of purification steps varies for every system, and several aspects need to be considered when designing a pharmaceutical water system:

1. Source water

 - Quality

 - Seasonal changes

 - Microbial control methods

2. Green engineering

3. Risk factors to the end product

4. Cost

 - Capital

 - Available resources

 - Operating costs

5. Required volume and quality of water

 - Peak, average, shutdown volumes

 - Types of water, compendial requirements

 - Temperature

6. Uses of water

 - Compendial ingredient

 - Cleaning/rinsing/washing

 - Humidification

7. Redundancy

8. Future capacity

Read also: Water for Pharmaceutical Use

No single design will meet every requirement or is guaranteed to produce the appropriate water quality. A pharmaceutical water system must have the capability to deliver safe water consistently and confidently, based on knowledge of source water and produced water, good engineering practices and water system design, good monitoring/control programs, and proper sanitization/maintenance.

General Information on Water Sources and Contaminants

The water supply to a municipality for the production of drinking water can vary substantially depending on whether it is ground or surface water and if it is in an area that is subject to seasonal variations or drought/monsoon conditions. This guide considers ground and surface water and the contaminants that can be found in those waters.

Water sources for production of potable (drinking) water

Ground waters
  • Higher mineral content
  • Low organic levels
  • Higher hardness levels
  • Less temperature variation

Surface waters
  • Lower mineral content
  • Higher organic levels
  • Higher TDS levels
  • Wide temperature variations
  • Seasonal fluctuations

Contaminants in water

Due to wide variations in source waters and because of water’s unique chemical properties, there is no pure water in nature. Water has unique chemical properties due to its polarity and hydrogen bonds. This means it is able to dissolve, absorb, adsorb or suspend many different compounds. These include contaminants that may represent hazards in themselves or that could react with the intended solution, drug or product. There are more than 90 possible unacceptable contaminants in potable water which are listed by government health authorities.
  • Total dissolved solids (TDS)
  • Total ionized solids and gases
  • Total solids
  • Microbial
  • Particulates
  • Organics

Production Requirements for Bulk Waters 

A facility must determine the type of bulk water they require and design the system such that it will be compliant at all times. To ensure continuous compliance, the performance of a pharmaceutical water purification, storage, and distribution system must be monitored.

The type of bulk water being produced determines the purification technologies that should be incorporated into a system. For PW the system can incorporate any combination of technologies, but specific water quality requirements must be met. For example, WFI should use distillation as the final purification step. The one exception is for WFI for use in Japan only, where a combination of reverse osmosis and ultrafiltration when fed PW can be the final purification step. HPW is a Europe only water type which can be used for very limited pharmaceutical applications.

Basic water system monitoring requirements

  • Monitoring of water sources regularly
 - chemical and microbiological
 - endotoxin (pyrogen) level where relevant
  • Monitoring of system performance, storage, and distribution systems
  • Records of results, and any actions taken
  • Validated sanitization procedures followed on a routine basis


Free-swimming aquatic bacteria use polymucosaccharides as a glue to colonize surfaces and form a biofilm. Biofilm is composed of cellular debris, organic material and a small number of vegetative cells.

Complex communities evolve which, when mature, shed micro-colonies and bacteria. This gives rise to sporadic high counts in bacteria levels. The major groups of water borne contaminants are algae, protozoa and bacteria.

Water treatment equipment, storage, and distribution systems used for PW, HPW and WFI should be provided with features to control the proliferation of microbiological organisms during normal use, and incorporate techniques for sanitizing or sterilizing the system after intervention for maintenance or modification. The techniques employed should be considered during the design of the system and their performance proven during the commissioning and qualification activities.

Resource: Mettler Toledo
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