A handy guide to validating high purity water systems

Water is the most widely used raw material in the production of pharmaceuticals, and in some products, like parenterals, it’s a vital element. Water is also used to clean vessels and systems used to manufacture pharma products.

A unique aspect of high purity water used in the pharma industry is that it’s possibly the only element, which, as a rule, must be produced by the drug manufacturers themselves as it’s not available in ready to use form.

Irrespective of the system used to generate high purity water, regulatory guidelines around the world mandate validation of the system. Validation is necessary to monitor system performance including that of storage and distribution systems. It ensures the system is operating within design parameters along with the consistent production of water of a desired quality. Validation also prevents unacceptable microbial, chemical and physical impurities from being generated during water generation, storage and distribution.

It allows manufacturers to prove the performance of processes or systems under all conditions, encountered during future operations. This is achieved by consistently producing the same quantity and quality of water during operations and maintaining this according to specific written operating and maintenance procedures.

The following factors are involved in proving the validation of high purity water systems:

• engineering design

• operating procedures and acceptable ranges for control parameters

• maintenance procedures to accomplish it

• the system has to be designed, installed and successfully tested in all operating conditions

• variations in daily, weekly and annual usage patterns must be validated.

A validation report is written at the conclusion of equipment, instrumental and operational qualification and at the completion of the validation protocol. This report serves as the primary document during inspection by the regulator and as a reference document if any changes are made to the system and revalidation is needed.

Documentation required

During validation, the following documentation is required:

• verification of design documentation including a description of installation and functions and specifications of functions

• operating procedures

• maintenance instructions and records

• training of personnel

• environmental records

• plant inspection documentation.

Once validation is complete, an effective standard operating procedure (SOP) is finalised, with the assurance that the system can consistently produce water according to specification and over long periods. If any deviations from the SOP are observed, it’s necessary to determine the change and impact on the whole system and carry out revalidation based on the change and impact.

Any validation protocol must include the elements outlined above. However, the validation process is long and often small details can be overlooked.

A reverse osmosis system installed within a pharmaceutical processing plant